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OpenTrials
Completed

NCT Number: NCT02647281

First Time in Human Study to Assess the Safety, Tolerability and Pharmacokinetics of GSK3389404 in Healthy Subjects

This study is a Phase 1, randomized, double-blind (Sponsor unblinded), placebo controlled, dose escalation study to determine the safety, tolerability and pharmacokinetics (PK) profile of GSK3389404 as single (Part 1) and multiple subcutaneous (SC) injections (Part 2) in healthy subjects. This study represents the first administration of GSK3389404 in humans to define the safety, tolerability and PK following single and multiple doses of GSK3389404 in healthy subjects.

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Key information

Conditions

Hepatitis B Blood-Borne Infections Communicable Diseases DNA Virus Infections Digestive System Diseases Hepadnaviridae Infections Hepatitis Hepatitis, Viral, Human Infections Liver Diseases Virus Diseases

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site, London, United Kingdom

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned.
  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and electrocardiograms (ECGs). There should be no evidence of cardiac, pulmonary, hepatic, biliary, gastrointestinal, or renal disorders, or cancer within the past 5 years (except localized or in situ cancer of the skin). A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria and are reported as outside of the normal reference range for healthy subjects may be included only if the Investigator considers the finding unlikely to introduce additional risk to the subject and will not interfere with the study procedures.
  • Male or female between 18 and 55 years of age, inclusive, at the time of signing the informed consent form (ICF).
  • Body weight >50 kilograms (kg) (110 pounds [lb]) for men and >45 kg (99 lb) women and a body mass index (BMI) between 18 to 30 kg/meter-squared, inclusive, will be allowed.
  • AST, ALT, ALP, bilirubin, and creatinine within the normal reference range. If outside the normal reference range, these values may be repeated once at the discretion of the Investigator or designee.
  • WBC count (including neutrophil counts), haemoglobin and platelets within the normal reference range. If outside the normal reference range, these values may be repeated once at the discretion of the Investigator or designee.
  • Females of Reproductive Potential (FRP) are not permitted. Eligible females must meet the following criteria:
  • Non-pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test); AND
  • Non-lactating at screening and prior to dosing; AND
  • Non-reproductive potential as defined by at least one of the following conditions: Pre-menopausal females without reproductive potential defined by one of the following: Documented salpingectomy, Hysterectomy, Documented bilateral oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea; A blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels may be conducted at the discretion of the Investigator or site to confirm non-reproductive potential.
  • Male subjects with female partners of child-bearing potential must agree to meet one of the contraception requirements from the time of first dose of study treatment until the last follow-up visit (Part 1 Day 60; Part 2 Day 113).
  • Vasectomy with documentation of azoospermia.
  • Male condom plus partner use of one of the contraceptive options below that meets the standard operating procedure (SOP) effectiveness criteria including a <1% rate of failure per year, as stated in the product label: Contraceptive subdermal implant; Intrauterine device or intrauterine system; Combined estrogen and progestogen oral contraceptive; Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The Investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.

Exclusion criteria

  • History or other clinical evidence of hypertension, significant or unstable cardiac disease (e.g., prolonged QT syndrome [torsade de pointes], angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease and/or clinically significant ECG abnormalities).
  • History of, or active diagnosis of, liver disease such as Gilbert's syndrome, cirrhosis, autoimmune hepatitis, non-alcoholic fatty liver disease /non-alcoholic steatohepatitis, or hemochromatosis.
  • History of, or active diagnosis of, primary or secondary (e.g., renal disease secondary to diabetes, hypertension, vascular disease, etc.) renal disease.
  • History of bleeding diathesis or coagulopathy.
  • History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Unwilling to abstain from alcohol for 48 hours prior to the start of dosing until the last dose in each dosing session.
  • Regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
  • History of sensitivity to GSK3389404 or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • Use of prescription or non-prescription drugs, including vitamin, dietary and herbal supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study treatment.
  • Use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) within 7 days prior to the first dose of study treatment.
  • A positive hepatitis C antibody.
  • A positive pre-study Hepatitis B surface antigen (HBsAg).
  • A positive test for human immunodeficiency virus (HIV) antibody.
  • Serum creatinine greater than the upper limit of normal (ULN)
  • Glomerular filtration rate <90 mL/minute as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-epi) formula
  • Albumin to creatinine ratio (ACR) >= 0.03 milligram/milligram (mg/mg). In the event of an ACR above this threshold, eligibility may be confirmed by a second measurement.
  • Qualitative test (urinalysis) for blood in urine >= 0.03 mg/deciliter. In the event of a positive test, the test may be repeated once, and if negative, the subject considered eligible.
  • A positive pre-study drug screen. Unwilling to refrain from use of the illicit drugs and adhere to other protocol-stated restrictions while participating in the study.
  • Fridericia's QT correction formula (QTcF) >= 450 milliseconds (msec).
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives (if known) or twice the duration (if known) of the biological effect of the study drug (whichever is longer) or 90 days (if half-life or duration is unknown).
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Prior treatment with any oligonucleotide or small interfering ribonucleic acid (siRNA) within 12 months prior to the first dosing day.

Treatment and study plan

GSK3389404

Drug

GSK3389404 is supplied as solution for injection vial. Each vial contains 100 mg/mL of GSK3389404. It's physical appearance is clear colourless to slightly yellow solution.

Matching Placebo

Drug

Placebo is supplied as solution for injection vial. It's physical appearance is clear colourless solution.

Primary outcomes

  1. Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1

    Time frame: Up to 62 days

    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. Participants who received any of the study treatment and had any AE or SAE or AELD were considered for analysis. Safety Population comprised of all participants who received at least 1 dose of study treatment.

  2. Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2

    Time frame: Up to 115 days

    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. Participants who received any of the study treatment and had any AE or SAE or AELD were considered for analysis.

  3. Number of Participants With Laboratory Values of Potential Clinical Importance in Part 1

    Time frame: Up to 62 days

    Blood samples were collected for hematology, clinical chemistry, coagulation parameters and urinalysis. Abnormalities of potential clinical importance were evaluated as per Division of Acquired Immune Deficiency Syndrome [DAIDS] table for grading the severity of adult and pediatric adverse events. Laboratory abnormalities of DAIDS Grade 1 or higher were considered as of potential clinical importance and were summarized.

  4. Number of Participants With Laboratory Values of Potential Clinical Importance in Part 2

    Time frame: Up to 115 days

    Blood samples were collected for hematology, clinical chemistry, coagulation parameters and urinalysis. Abnormalities of potential clinical importance were evaluated as per DAIDS table for grading the severity of adult and pediatric adverse events. Laboratory abnormalities of DAIDS Grade 1 or higher were considered as of potential clinical importance and were summarized.

  5. Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1

    Time frame: Day 1 (pre-dose) and up to 31 days

    Blood samples were collected to evaluate complement factors (C3 and C4) levels. Latest pre-dose assessment at Day 1 was considered as Baseline value. Change from Baseline was calculated as difference between minimum level (lowest of the measurements for specimens collected) observed post-dose and pre-study drug administration.

  6. Change From Baseline in Complement Split Product C5a Levels in Part 1

    Time frame: Day 1 (pre-dose) and up to 31 days

    Blood samples were collected to evaluate complement split product C5a levels. Latest pre-dose assessment at Day 1 was considered as Baseline value. Change from Baseline was calculated as difference between maximum level (highest of the measurements for specimens collected) observed post-dose and pre-study drug administration.

  7. Change From Baseline in Complement Split Product Bb Levels in Part 1

    Time frame: Day 1 (pre-dose) and up to 31 days

    Blood samples were collected to evaluate complement split product Bb levels. Latest pre-dose assessment at Day 1 was considered as Baseline value. Change from Baseline was calculated as difference between maximum level (highest of the measurements for specimens collected) observed post-dose and pre-study drug administration

  8. Change From Baseline in Complement Factor C3 and C4 Levels in Part 2

    Time frame: Day 1 (pre-dose) and Day 22

    Blood samples were collected to evaluate complement factors (C3 and C4) levels. Latest pre-dose assessment at Day 1 or Day 22 was considered as Baseline value. Change from Baseline was calculated as difference between minimum level (lowest of the measurements for specimens collected each after Day 1 and Day 22 study drug administrations) observed post-dose and pre-study drug administration

  9. Change From Baseline in Complement Factor C5a Levels in Part 2

    Time frame: Day 1 (pre-dose) and Day 22

    Blood samples were collected to evaluate complement factors C5a levels. Latest pre-dose assessment at Day 1 or Day 22 was considered as Baseline value. Change from Baseline was calculated as difference between maximum level (lowest of the measurements for specimens collected each after Day 1 and Day 22 study drug administrations) observed post-dose and pre-study drug administration.

  10. Change From Baseline in Complement Factor Bb Levels in Part 2

    Time frame: Day 1 (pre-dose) and Day 22

    Blood samples were collected to evaluate complement factors C5a levels. Latest pre-dose assessment at Day 1 or Day 22 was considered as Baseline value. Change from Baseline was calculated as difference between maximum level (lowest of the measurements for specimens collected each after Day 1 and Day 22 study drug administrations) observed post-dose and pre-study drug administration.

  11. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1

    Time frame: Day 1 (pre-dose) and up to 30 days

    SBP and DBP were taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 8, 12, 24, 48 and 72 hour post dose; and on Days 8 and 30. Measurements were obtained after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  12. Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1

    Time frame: Day 1 (pre-dose) and up to 30 days

    Pulse rate was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 8, 12, 24, 48 and 72 hour post dose; and on Days 8 and 30. Measurements were obtained after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  13. Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1

    Time frame: Day 1 (pre-dose) and up to 30 days

    Respiratory rate was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 8, 12, 24, 48 and 72 hour post dose; and on Days 8 and 30. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  14. Change From Baseline in Body Temperature at the Indicated Time Points in Part 1

    Time frame: Day 1 (pre-dose) and up to 30 days

    Temperature was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 8, 12, 24, 48 and 72 hour post dose; and on Days 8 and 30. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  15. Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2

    Time frame: Day 1 (pre-dose) and up to 115 days

    SBP and DBP were taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 6, 8, 12, 24, 48 and 72 hour post Day 1 dose; on Days 8 and 15; Day 22 (pre-dose) and at 1, 4, 6, 12, 24, 48 and 72 hours post Day 22 dose; on Days 29, 36, 50, 71 and at Follow-up visit (Day 113 +- 2 days). Measurements were obtained after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  16. Change From Baseline in PR at the Indicated Time Points in Part 2

    Time frame: Day 1 (pre-dose) and up to 115 days

    Pulse rate was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 6, 8, 12, 24, 48 and 72 hour post Day 1 dose; on Days 8 and 15; Day 22 (pre-dose) and at 1, 4, 6, 12, 24, 48 and 72 hours post Day 22 dose; on Days 29, 36, 50, 71 and at Follow-up visit (Day 113+- 2 days). Measurements were obtained after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  17. Change From Baseline in RR at the Indicated Time Points in Part 2

    Time frame: Day 1 (pre-dose) and up to 115 days

    Respiratory rate was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 6, 8, 12, 24, 48 and 72 hour post Day 1 dose; on Days 8 and 15; Day 22 (pre-dose) and at 1, 4, 6, 12, 24, 48 and 72 hours post Day 22 dose; on Days 29, 36, 50, 71 and at Follow-up visit (Day 113+- 2 days). Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  18. Change From Baseline in Body Temperature at the Indicated Time Points in Part 2

    Time frame: Day 1 (pre-dose) and up to 115 days

    Body temperature was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 6, 8, 12, 24, 48 and 72 hour post Day 1 dose; on Days 8 and 15; Day 22 (pre-dose) and at 1, 4, 6, 12, 24, 48 and 72 hours post Day 22 dose; on Days 29, 36, 50, 71 and at Follow-up visit (Day 113+- 2 days). Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  19. Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1

    Time frame: Day 1 (pre-dose) and up to 31 days

    12-lead ECGs were recorded at Baseline (Day 1, pre-dose) and at 1, 4, 8, 12, 24 and 48 hour post dose; and on Days 8 and 30. Measurements were obtained after resting for at least 5 minutes in a supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants with worst change from Baseline in ECG have been presented as clinically significant (CS) change or not a clinically significant (NCS) change.

  20. Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose

    Blood samples were collected to evaluate AUC (0-inf), AUC (0-t) and AUC (0-24) of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose. Pharmacokinetic Concentration Population was defined as participants who underwent plasma PK sampling and had evaluable PK assay results post-dose.

  21. Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose

    Blood samples were collected to evaluate Cmax, C24 and C168 of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose.

  22. Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose

    Blood samples were collected to evaluate Tmax, T1/2 and Tlag of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose.

  23. Apparent SC Plasma Clearance (CL/F) of GSK3389404 Following Single Dose in Part 1

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose

    Blood samples were collected to evaluate CL/F of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose.

  24. AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose

    Blood samples were collected to evaluate AUC (0-t), AUC (0-24), AUC (0-168) and AUC (0-inf) of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose.

  25. Cmax, C24 and C168 of GSK3389404 Following Single Dose on Day 1 of Part 2

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose

    Blood samples were collected to evaluate Cmax, C24 and C168 of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose.

  26. Tmax, T1/2 and Tlag of GSK3389404 Following Single Dose on Day 1 of Part 2

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose

    Blood samples were collected to evaluate Tmax, T1/2 and Tlag of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose.

  27. CL/F of GSK3389404 Following Single Dose on Day 1 of Part 2

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose

    Blood samples were collected to evaluate CL/F of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose. Only those participants with data available at the specified time points were analyzed.

  28. AUC(0-24) and AUC From Time Zero to the End of the Dosing Interval [AUC(0-tau)] of GSK3389404 Following Dosing on Day 22 of Part 2

    Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)

    Blood samples were collected to evaluate AUC (0-24) and AUC (0-tau) of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days ).

  29. Observed Concentration at the End of the Dosing Interval (Ctau), C24 and Cmax of GSK3389404 Following Dosing on Day 22 of Part 2

    Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)

    Blood samples were collected to evaluate Ctau, C24 and Cmax of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days ).

  30. Tmax, T1/2 and Tlag of GSK3389404 Following Dosing on Day 22 of Part 2

    Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)

    Blood samples were collected to evaluate Tmax, T1/2 and Tlag of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days).

  31. Cl/F of GSK3389404 Following Dosing on Day 22 of Part 2

    Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)

    Blood samples were collected to evaluate Cl/F of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days).

Secondary outcomes

  1. Dose Proportionality of GSK202007 for Dose Range 10 mg - 120 mg After Single Dose Administrations

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose; Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose in Part 2.

    Results of dose proportionality assessment using power model and analysis of variance (ANOVA) following single dose administariton (Part 1 and Day 1 in Part 2) are presented. Slope estimates and 90% confidence interval are presented for combined data of Day 1 of Part 1 and 2.

  2. Dose Proportionality of GSK202007 for Dose Range 30 mg - 120 mg After Multiple Dose Administrations

    Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115) in Part 2

    Results of proportionality assessment using power model and ANOVA following multiple doses are presented. Slope estimates and 90% confidence interval are presented for Day 22 of Part 2.

  3. Accumulation Ratio by AUC (RAUC), by Cmax (RCmax), by C24 (RC24) and by Ctau (RCtau) of GSK3389404 in Part 2

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose; Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)

    For Part 2, the extent of accumulation of GSK3389404 was evaluated by comparing AUC (0-tau), Cmax, C24 and Ctau on Day 22 to AUC (0-168), Cmax, C24 and C168 on Day 1. For each dose level, a linear mixed effect model was fitted with the log transformed PK parameter as the dependent variable, day as a fixed effect and subject as a random effect.

  4. Time Invariance (LI) of GSK3389404 in Part 2

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose; Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)

    For Part 2, time invariance was evaluated by comparing AUC (0-tau) for Day 22 to AUC (0-inf) for Day 1. For each dose level, a linear mixed effect model was fitted with the log transformed PK parameter as the dependent variable, day as a fixed effect and subject as a random effect. Only those participants with data available at the specified time points were analyzed.

  5. Trough Plasma Concentrations of GSK3389404 in Part 2

    Time frame: Pre-dose on Days 8, 15, 22 and 29

    For Part 2, mean plasma GSK3389404 pre-dose values between Day 1 to Day 29 and Ctau were plotted against time to assess attainment of GSK3389404 steady state following multiple dose administration. Achievement of plasma GSK3389404 steady-state was assessed by calculating the 90% confidence interval (CI) of the slope of the linear regression of log (Ctau) versus time. NA indicates data was not available.

  6. AUC (0-inf), AUC(0-t), AUC(0-24) of the Metabolite of GSK3389404 After Single Dose in Part 1

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose

    Blood samples were collected to evaluate AUC (0-inf), AUC (0-t) and AUC (0-24) of metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose.

  7. Cmax, C24 and C168 of the Metabolite of GSK3389404 Following Single Dose in Part 1

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose

    Blood samples were collected to evaluate Cmax, C24 and C168 of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose.

  8. Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Single Dose in Part 1

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose

    Blood samples were collected to evaluate Tmax, T1/2 and Tlag of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose.

  9. AUC (0-t), AUC(0-24), AUC(0-168) and AUC (0-inf) of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose

    Blood samples were collected to evaluate AUC (0-t), AUC (0-24), AUC (0-168) and AUC (0-inf) of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose.

  10. Cmax, C24 and C168 of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose

    Blood samples were collected to evaluate Cmax, C24 and C168 of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose.

  11. Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2

    Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose

    Blood samples were collected to evaluate Tmax, T1/2 and Tlag of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose.

  12. AUC(0-24) and AUC(0-tau) of the Metabolite of GSK3389404 Following Dosing of GSK3389404 on Day 22 of Part 2

    Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)

    Blood samples were collected to evaluate AUC (0-24) and AUC (0-tau) of the metabolite of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days).

  13. Ctau, C24 and Cmax of the Metabolite of GSK3389404 Following Dosing of GSK3389404 on Day 22 of Part 2

    Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)

    Blood samples were collected to evaluate Ctau, C24 and Cmax of the metabolite of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days).

  14. Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Dosing on Day 22 of Part 2

    Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)

    Blood samples were collected to evaluate Tmax, T1/2 and Tlag of the metabolite of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days).

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

A Double-Blind, Placebo-Controlled, Dose-Escalation, First Time in Human Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of GSK3389404 in Healthy Subjects

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Jan 6, 2016
Registry last updated
Jul 16, 2019

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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