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Completed

NCT Number: NCT03784079

A Proof of Concept Study of GSK3640254 in Human Immunodeficiency Virus-1 (HIV-1) Infected Treatment-naive Adults

Infection with HIV-1 continues to be a serious health threat throughout the world. Chronic exposure to combination anti-retroviral therapy identified anti-retroviral associated long-term toxicities. Hence, there is a need to prevent these co-morbidities. GSK3640254 is a next-generation HIV-1 Maturation Inhibitor (MI) which may be effective for HIV-1 infection. This study will evaluate the antiviral effect, safety, tolerability and pharmacokinetics/ pharmacodynamics of GSK3640254 in HIV-1 infected treatment-naive adults. This study will consists of two parts; Part 1 and Part 2. Part 1 will evaluate two active doses of GSK3640254, 200 milligrams (mg) (Cohort 1) and 10 mg (Cohort 2) along with placebo to match GSK3640254 Mesylate salt. Part 2 will evaluate three active doses of GSK3640254. Dose level 1 of GSK3640254 that can provide at least 30 percent of the maximum effect (Cohort 1), dose level 2 of GSK3640254 that can provide at least 75 percent of the maximum effect (Cohort 2) and dose level 3 of GSK3640254 that can provide at least 90 percent of the maximum effect (Cohort 3). These doses are anticipated to be 5 mg, 40 mg and 100 mg respectively, but could be modified based on data obtained in Part 1. Subjects will also receive placebo to match GSK3640254 Mesylate salt in Part 2 of the study. All doses will be administered after a moderate fat meal. This study will consist of Screening period (up to 14 days), Treatment period (Day 1- Day 10), post-dose Follow-up (Day 11- Day 17) and final Follow-up (Day 18-24). A total of approximately 34 subjects will be enrolled, of which, 14 subjects will be randomized in Part 1 and 20 in Part 2 of the study. Six subjects will be enrolled in each of the active dose cohorts and 2 subjects will be enrolled in each of the placebo cohorts.

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Key information

Conditions

HIV Infections Blood-Borne Infections Communicable Diseases Genital Diseases Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

GSK Investigational Site, Marseille, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
  • Subjects who are healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, laboratory tests, and cardiac monitoring.
  • Screening Cluster of designation 4 positive (CD4+) T-cell count >=350 cells per millimeter cube (cells/mm^3).
  • Documented HIV infection and Screening plasma HIV-1 RNA >=5000 copies/milliliter (mL). A single repeat of this test is allowed within a single Screening period to determine eligibility.
  • Treatment-naive: No anti-retrovirals (in combination or monotherapy) received after the diagnosis of HIV-1 infection.
  • Body weight >=50.0 kilograms (kg) (110 Pounds) for men and >=45.0 kg (99 pounds) for women and body mass index (BMI) within the range 18.5-31.0 kg/meter square (kg/m^2) (inclusive).
  • A female subject is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP).
  • Capable of giving signed informed consent.
  • For subjects enrolled in France: a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion criteria

  • Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to starting study treatment.
  • Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment and positive on reflex to Hepatitis C RNA.
  • ALT >2 times upper limit of normal (ULN). A single repeat of ALT is allowed within a single Screening period to determine eligibility.
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
  • Subjects with primary HIV infection, evidenced by acute retroviral syndrome (example given [e.g.], fever, malaise, fatigue, etc) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones);
  • A pre-existing condition interfering with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease [GERD], gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs or render the subject unable to take oral study treatment.
  • Any acute laboratory abnormality at screen which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
  • Any Grade 2-4 laboratory abnormality at screen, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides, etc), and ALT (described above), will exclude a subject from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any lab abnormality is allowed within a single screening period to determine eligibility.
  • Any history of significant underlying psychiatric disorder, including but not limited to schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
  • Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment. Subjects with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the ViiV Medical Monitor.
  • Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject.
  • Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
  • The subject has participated in a clinical trial and has received an investigational product within the 30 days prior to the first dosing day in the current study.
  • Any positive (abnormal) response confirmed by the investigator on a Screening clinician- (or qualified designee-) administered Columbia Suicide Severity Rating Scale (CSSRS).
  • Any positive result for illicit drug use (e.g., cocaine, heroin) at Screening. A positive screen for marijuana is not exclusionary, though if positive for delta-9-tetrahydrocannabinol (THC).
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
  • Exposure to more than four new investigational drugs or vaccines within 12 months prior to the first dosing day.
  • Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or anticipated need for such treatment within the study.
  • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; or other localized malignancies require agreement between the investigator and the study medical monitor for inclusion of the subject prior to randomization.
  • Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration.
  • An active Center for Disease Control and Prevention (CDC) Category C disease except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial.
  • Treatment with any vaccine within 30 days prior to receiving study medication.
  • Exclusion criteria for screening electrocardiogram (a single repeat is allowed for eligibility determination): Heart rate of <45 or >100 beats per minute (bpm) for males and <50 or >100 bpm for females; PR Interval of <120 or >200 milliseconds (msec) for both males and females; QRS duration of <70 or >110 msec for both males and females; QT interval corrected (QTc) for heart rate according to Fridericia's formula (QTcF) of >450 msec for males and >470 msec for females. A heart rate from 100 to 110 bpm can be rechecked by electrocardiogram or vitals within 30 minutes to verify eligibility. QTcF is either machine read or manually over-read.
  • Any significant arrhythmia or electrocardiogram finding (e.g., prior myocardial infarction, sinoatrial pauses, bundle branch block, or conduction abnormality) which, in the opinion of the Investigator OR ViiV Medical Monitor, will interfere with the safety for the individual subject.

Treatment and study plan

GSK3640254

Drug

GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.

Placebo matching GSK3640254 Mesylate salt

Drug

Placebo to match GSK3640254 Mesylate salt will be given as an oral capsule along with 240 mL of water

Primary outcomes

  1. Part 1: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11

    Time frame: Baseline (Day 1) and Day 11

    Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. A HIV-1 RNA polymerase chain reaction (PCR) assay with a lower limit of detection (LLOD) of 50 copies per milliliter was used. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  2. Part 2: Maximum Change From Baseline in Plasma HIV-1 RNA at Day 8

    Time frame: Baseline (Day 1) and Day 8

    Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. An HIV-1 RNA PCR assay with an LLOD of 50 copies per milliliter was used. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Secondary outcomes

  1. Part 1: Number of Participants With Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

    Time frame: Up to Day 24

    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per Medical or scientific judgment. Safety Population consisted of all participants who were enrolled into the study with documented evidence of having received at least 1 dose of randomized treatment.

  2. Part 2: Number of Participants With Non-SAEs and SAEs

    Time frame: Up to Day 12

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per Medical or scientific judgment.

  3. Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  4. Part 1: Change From Baseline in Hematology Parameter: Hemoglobin

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  5. Part 1: Change From Baseline in Hematology Parameter: Hematocrit

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  6. Part 1: Change From Baseline in Hematology Parameter: Erythrocytes

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  7. Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  8. Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  9. Part 1: Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocyte

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: reticulocytes/erythrocyte (erythro). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  10. Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  11. Part 2: Change From Baseline in Hematology Parameter: Hemoglobin

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  12. Part 2: Change From Baseline in Hematology Parameter: Hematocrit

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  13. Part 2: Change From Baseline in Hematology Parameter: Erythrocytes

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  14. Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  15. Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  16. Part 2: Change From Baseline in Hematology Parameter: Reticulocytes/Erythro

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  17. Part 1: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  18. Part 1: Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  19. Part 1: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  20. Part 1: Change From Baseline in Chemistry Parameters: Protein

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  21. Part 1: Change From Baseline in Chemistry Parameters: Amylase, Lipase

    Time frame: Baseline (Day 1) and Visit 6 (Day 11)

    Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  22. Part 2: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  23. Part 2: Change From Baseline in Chemistry Parameters: ALT, ALP, AST

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  24. Part 2: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  25. Part 2: Change From Baseline in Chemistry Parameters: Protein

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  26. Part 2: Change From Baseline in Chemistry Parameters: Amylase, Lipase

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  27. Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  28. Part 1: Change From Baseline in Urinalysis Parameter: Urobilinogen

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  29. Part 1: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  30. Part 2: Change From Baseline in Urinalysis Parameter: Specific Gravity

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  31. Part 2: Change From Baseline in Urinalysis Parameter: Urobilinogen

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Urine samples were collected to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  32. Part 2: Change From Baseline in Urinalysis Parameter: pH

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  33. Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  34. Part 1: Change From Baseline in Respiratory Rate

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  35. Part 1: Change From Baseline in Pulse Rate

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  36. Part 2: Change From Baseline in SBP and DBP

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  37. Part 2: Change From Baseline in Respiratory Rate

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  38. Part 2: Change From Baseline in Pulse Rate

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  39. Part 1: Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB), Corrected QT Interval Using Fridericia's Formula (QTcF)

    Time frame: Baseline (Day 1), Visit 5 (Days 8 to 10: Pre-dose, 2, 4 and 6 hours)

    Twelve lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcB Interval and QTcF Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  40. Part 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcB, QTcF

    Time frame: Baseline (Day 1), Visit 5 (Day 7: Pre-dose, 2, 4 and 6 hours)

    Twelve lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcB Interval and QTcF Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  41. Part 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  42. Part 1: Absolute Values for Hematology Parameter: Hemoglobin

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  43. Part 1: Absolute Values for Hematology Parameter: Hematocrit

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  44. Part 1: Absolute Values for Hematology Parameter: Erythrocytes

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  45. Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  46. Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  47. Part 1: Absolute Values for Hematology Parameter: Reticulocytes/Erythro

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  48. Part 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  49. Part 2: Absolute Values for Hematology Parameter: Hemoglobin

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  50. Part 2: Absolute Values for Hematology Parameter: Hematocrit

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  51. Part 2: Absolute Values for Hematology Parameter: Erythrocytes

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  52. Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  53. Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  54. Part 2: Absolute Values for Hematology Parameter: Reticulocytes/Erythro

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  55. Part 1: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  56. Part 1: Absolute Values for Chemistry Parameters: ALT, ALP, AST

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  57. Part 1: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  58. Part 1: Absolute Values for Chemistry Parameters: Protein

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  59. Part 1: Absolute Values for Chemistry Parameters: Amylase, Lipase

    Time frame: Baseline (Day 1) and Visit 6 (Day 11)

    Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  60. Part 2: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  61. Part 2: Absolute Values for Chemistry Parameters: ALT, ALP, AST

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  62. Part 2: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  63. Part 2: Absolute Values for Chemistry Parameters: Protein

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  64. Part 2: Absolute Values for Chemistry Parameters: Amylase, Lipase

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  65. Part 1: Absolute Values for Urinalysis Parameter: Specific Gravity

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  66. Part 1: Absolute Values for Urinalysis Parameter: Urobilinogen

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  67. Part 1: Absolute Values for Urinalysis Parameter: pH

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  68. Part 2: Absolute Values for Urinalysis Parameter: Specific Gravity

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  69. Part 2: Absolute Values for Urinalysis Parameter: Urobilinogen

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Urine samples were collected to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  70. Part 2: Absolute Values for Urinalysis Parameter: pH

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  71. Part 1: Absolute Values for SBP and DBP

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  72. Part 1: Absolute Values for Respiratory Rate

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  73. Part 1: Absolute Values for Pulse Rate

    Time frame: Baseline (Day 1) and Visit 5 (Days 8 to 10)

    Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  74. Part 2: Absolute Values for SBP and DBP

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  75. Part 2: Absolute Values for Respiratory Rate

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  76. Part 2: Absolute Values for Pulse Rate

    Time frame: Baseline (Day 1) and Visit 5 (Day 7)

    Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  77. Part 1: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF Intervals

    Time frame: Baseline (Day 1), Visit 5 (Days 8 to 10: Pre-dose, 2, 4 and 6 hours)

    Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval and QTcB interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  78. Part 2: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF Intervals

    Time frame: Baseline (Day 1), Visit 5 (Day 7: Pre-dose, 2, 4 and 6 hours)

    Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval and QTcB interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  79. Part 1: Area Under the Plasma Concentration Time Curve From Zero to 24 (AUC[0-24]) Following Administration of GSK3640254 on Day 1

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Pharmacokinetic (PK) Population consisted of all participants who received GSK3640254 and underwent plasma PK sampling during the study.

  80. Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK3640254 on Day 1

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  81. Part 1: Time to Maximum Observed Concentration (Tmax) Following Administration of GSK3640254 on Day 1

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  82. Part 1: Concentration at 24 Hours Post-dose (C24) Following Administration of GSK3640254 on Day 1

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  83. Part 1: Absorption Lag Time (Tlag) Following Administration of GSK3640254 on Day 1

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  84. Part 2: AUC(0-24) Following Administration of GSK3640254 on Day 1

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  85. Part 2: Cmax Following Administration of GSK3640254 on Day 1

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  86. Part 2: Tmax Following Administration of GSK3640254 on Day 1

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  87. Part 2: C24 Following Administration of GSK3640254 on Day 1

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  88. Part 2: Tlag Following Administration of GSK3640254 on Day 1

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  89. Part 1: Area Under the Plasma Drug Concentration-time Curve From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

    Time frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  90. Part 1: Cmax Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

    Time frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  91. Part 1: Tmax Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

    Time frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  92. Part 1: Pre-dose Concentration (C0) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

    Time frame: Days 8 to 10: Pre-dose

    Blood sample was collected at indicated time point for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  93. Part 1: Concentration at End of Dosing Interval (Ctau) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

    Time frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  94. Part 1: Apparent Terminal Phase Half-life (t1/2) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

    Time frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  95. Part 1: Apparent Oral Clearance (CL/F) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

    Time frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  96. Part 2: AUC(0-tau) Following Repeat Dose Administration of GSK3640254 on Day 7

    Time frame: Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  97. Part 2: Cmax Following Repeat Dose Administration of GSK3640254 on Day 7

    Time frame: Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  98. Part 2: Tmax Following Repeat Dose Administration of GSK3640254 on Day 7

    Time frame: Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  99. Part 2: C0 Following Repeat Dose Administration of GSK3640254 on Day 7

    Time frame: Day 7: Pre-dose

    Blood sample was collected at indicated time point for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  100. Part 2: Ctau Following Repeat Dose Administration of GSK3640254 on Day 7

    Time frame: Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  101. Part 2: t1/2 Following Repeat Dose Administration of GSK3640254 on Day 7

    Time frame: Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  102. Part 2: CL/F Following Repeat Dose Administration of GSK3640254 on Day 7

    Time frame: Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  103. Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 AUC(0-tau)

    Time frame: Baseline (Day 1) and Day 8

    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (AUC) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), PK parameter value that attains 50 percent (%) of the maximal effect (EC50) and residual variability (s2e). PK/PD Population consisted of participants who met criteria for Per-Protocol and Pharmacokinetic Population analysis sets and who underwent PD sampling during the study.

  104. Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Cmax

    Time frame: Baseline (Day 1) and Day 8

    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (Cmax) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: Emax, EC50 and s2e.

  105. Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Ctau

    Time frame: Baseline (Day 1) and Day 8

    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (Ctau) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: Emax, EC50 and s2e.

  106. Part 1: Accumulation Ratio Following Repeat Dose Administration of GSK3640254

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The accumulation ratios (Ro) were calculated as Ro_AUC equal to (=) AUC(0-tau) Days 8 to 10 divided by (/) AUC(0-24) Day 1; Ro_Cmax=Cmax Days 8 to 10/Cmax Day 1; and Ro_Ctau=Ctau Days 8 to 10/C24 Day 1.

  107. Part 2: Accumulation Ratio Following Repeat Dose Administration of GSK3640254

    Time frame: Days 1 and 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The accumulation ratios (Ro) were calculated as Ro_AUC=AUC(0-tau) Day 7/AUC(0-24) Day 1; Ro_Cmax=Cmax Day 7/Cmax Day 1; and Ro_Ctau=Ctau Day 7/C24 Day 1.

  108. Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on AUC(0-24)

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

  109. Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on Cmax

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

  110. Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on C24

    Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

  111. Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on AUC(0-tau)

    Time frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

  112. Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on Cmax

    Time frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

  113. Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on Ctau

    Time frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

Sponsors and collaborators

Lead sponsor

ViiV Healthcare

Industry

Registry information

Official study title

A Randomized, Double-Blind (Sponsor-unblinded), Placebo-Controlled, Adaptive Trial to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK3640254 in HIV-1 Infected Treatment-Naïve Adults

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Dec 21, 2018
Registry last updated
Feb 16, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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