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Completed

NCT Number: NCT03627494

First Time in Human (FTIH) Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of GSK3439171A in Healthy Subjects and to Assess Food Effect

The FTIH study with GSK3439171A will evaluate the safety of GSK3439171A in healthy subjects in order to avoid confounding factors due to the disease or concomitant drugs in patients. The study design is based on pre-clinical findings for GSK3439171A, contributing to the frequency, type and duration of safety assessment and monitoring during treatment periods in each cohort. The single dose assessments in Part A will be conducted to determine safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the study intervention in individuals before progressing to doses explored further in other parts of the study and will allow for any adjustments needed based on emerging safety, tolerability, and PK information. Part A will also serve to identify a dose for use in examining the effect of food on GSK3439171A exposure in Part C. In Part B, a single dose safety, tolerability and PK will be collected followed by progression of these subjects to the repeat dose portion of the study. The up to 14-day dosing was chosen as it is thought to provide sufficient safety and tolerability data to bridge to longer duration studies. The dosing period can be adjusted depending on PK and PD data collected in Part A of the study. Part B will involve more detailed PK/PD/metabolite assessments to better understand the impact of GSK3439171A on target engagement and metabolism in humans. Approximately 150 subjects will be screened to achieve 75 randomly assigned to study intervention. Duration for Part A, B and C will be approximately 10 weeks, 9 weeks and 8 weeks respectively.

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Key information

Conditions

Muscular Dystrophies Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Muscular Diseases Muscular Disorders, Atrophic Musculoskeletal Diseases Nervous System Diseases Neuromuscular Diseases

Age range

18 year–65 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Who can participate

Healthy volunteers accepted: Yes

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 overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) not specifically listed in the exclusion or exclusion criteria that is outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Subjects with Body weight >=50.0 kilograms (Kg) (110 lbs.) and body mass index (BMI) within the range 18.5 to 31.0 kilograms per square meter (inclusive).
  • Only male subjects are eligible for this study. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Male subjects are eligible to participate if they agree to the following during the their entire enrolment in the study plus an additional 5 days or 5 terminal half-lives (whichever is longer): Refrain from donating sperm plus either be abstinent from sexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception/barrier (female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year)
  • Subjects must be capable of giving signed informed consent

Exclusion criteria

  • Subjects are excluded from the study if they have history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
  • Subjects are excluded from the study if they have any clinically significant abnormal vital signs
  • Subjects are excluded from the study if they have Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years
  • Subjects are excluded from the study if they have ALT >1.5 times upper limit of normal (ULN)
  • Subjects are excluded from the study if Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
  • Subjects are excluded from the study if they have current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • Subjects are excluded from the study if they have QTc >450 milliseconds
  • Subjects who are unable to refrain from the use of prescription or non-prescription drugs, including aspirin, Non-steroidal Anti-inflammatory Drugs (NSAIDs), vitamins, herbal and dietary supplements (including St John's Wort) within 10 days prior to the first dose of study medication.
  • In cases, where participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 56 days
  • Subjects with exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Subjects with current enrolment or past participation within the last 30 days before signing of consent in this or any other clinical study involving an investigational study intervention or any other type of medical research.
  • Subjects with presence of Hepatitis B surface antigen (HBsAg) at screening.
  • Subjects with Positive Hepatitis C antibody test result at screening. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) test is obtained.
  • Subjects with Positive Hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention
  • Subjects with positive pre-study drug/alcohol screen
  • Subjects with positive human immunodeficiency virus (HIV) antibody test
  • Subjects with regular use of known drugs of abuse or positive urine drug test at screening or each in-house admission to the clinical research unit
  • Subjects with regular alcohol consumption within 6 months prior to screening and 5 days prior to admission defined as: An average weekly intake of > 14 units for males. One unit is equivalent to 8 gram of alcohol: a half-pint (Approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of 80 proof distilled spirits
  • Subjects with positive urinary cotinine test indicative of smoking history at screening or each in-house admission to the clinical research unit or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening
  • Subjects with sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Treatment and study plan

GSK3439171A

Drug

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo

Drug

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Primary outcomes

  1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A

    Time frame: Up to Day 40

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. 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; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.

  2. Number of Participants With AEs and SAEs-Part B

    Time frame: Up to Day 34

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. 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; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.

  3. Number of Participants With AEs and SAEs-Part C

    Time frame: Up to Day 29

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. 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; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.

  4. Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance-Part A

    Time frame: Up to Day 40

    Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: <30 grams per liter [g/L]); alanine aminotransferase (ALT) (high: >=2xupper limit of normal [ULN]); aspartate aminotransferase (AST) (high: >=2xULN); alkaline phosphatase (ALP) (high: >=2xULN); total bilirubin (high: >=1.5xULN); calcium (low: <2 millimoles (mmol)/L and high: >2.75 mmol/L); creatinine (high: change from Baseline >44.2 micromoles/L); glucose (low: <3 mmol/L and high: >9 mmol/L); magnesium (low: 0.5 mmol/L and high: 1.23 mmol/L); phosphorus (low: 0.8 mmol/L and high: 1.6 mmol/L); potassium (low: <3 mmol/L and high: >5.5 mmol/L); sodium (low: <130 mmol/L and high: >150 mmol/L) and creatine kinase (high: >500 units per liter). The number of participants with any clinical chemistry abnormality of potential clinical importance is reported.

  5. Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance-Part B

    Time frame: Up to Day 34

    Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: <30 g/L); ALT (high: >=2xULN); AST (high: >=2xULN); ALP (high: >=2xULN); total bilirubin (high: >=1.5xULN); calcium (low: <2 mmol/L and high: >2.75 mmol/L); creatinine (high: change from Baseline >44.2 micromoles/L); glucose (low: <3 mmol/L and high: >9 mmol/L); magnesium (low: 0.5 mmol/L and high: 1.23 mmol/L); phosphorus (low: 0.8 mmol/L and high: 1.6 mmol/L); potassium (low: <3 mmol/L and high: >5.5 mmol/L); sodium (low: <130 mmol/L and high: >150 mmol/L) and creatine kinase (high: >500 units per liter). The number of participants with any clinical chemistry abnormality of potential clinical importance is reported.

  6. Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance-Part C

    Time frame: Up to Day 29

    Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: <30 g/L); ALT (high: >=2xULN); AST (high: >=2xULN); ALP (high: >=2xULN); total bilirubin (high: >=1.5xULN); calcium (low: <2 mmol/L and high: >2.75 mmol/L); creatinine (high: change from Baseline >44.2 micromoles/L); glucose (low: <3 mmol/L and high: >9 mmol/L); magnesium (low: 0.5 mmol/L and high: 1.23 mmol/L); phosphorus (low: 0.8 mmol/L and high: 1.6 mmol/L); potassium (low: <3 mmol/L and high: >5.5 mmol/L); sodium (low: <130 mmol/L and high: >150 mmol/L) and creatine kinase (high: >500 units per liter). The number of participants with any clinical chemistry abnormality of potential clinical importance is reported.

  7. Number of Participants With Hematology Abnormalities of Potential Clinical Importance-Part A

    Time frame: Up to Day 40

    Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: >0.54 proportion of red blood cells in blood); hemoglobin (high: >180 g/L), lymphocytes (low: <0.8x10^9 cells per liter [cells/L]); neutrophil count (low: <1.5x10^9 cells/L); platelet count (low: <100x10^9 cells/L and high: >550x10^9 cells/L); white blood cells count (low: <3x10^9 cells/L and high: >20x10^9 cells/L). The number of participants with any hematology abnormality of potential clinical importance is reported.

  8. Number of Participants With Hematology Abnormalities of Potential Clinical Importance-Part B

    Time frame: Up to Day 34

    Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: >0.54 proportion of red blood cells in blood); hemoglobin (high: >180 g/L), lymphocytes (low: <0.8x10^9 cells/L); neutrophil count (low: <1.5x10^9 cells/L); platelet count (low: <100x10^9 cells/L and high: >550x10^9 cells/L); white blood cells count (low: <3x10^9 cells/L and high: >20x10^9 cells/L). The number of participants with any hematology abnormality of potential clinical importance is reported.

  9. Number of Participants With Hematology Abnormalities of Potential Clinical Importance-Part C

    Time frame: Up to Day 29

    Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: >0.54 proportion of red blood cells in blood); hemoglobin (high: >180 g/L), lymphocytes (low: <0.8x10^9 cells/L); neutrophil count (low: <1.5x10^9 cells/L); platelet count (low: <100x10^9 cells/L and high: >550x10^9 cells/L); white blood cells count (low: <3x10^9 cells/L and high: >20x10^9 cells/L). The number of participants with any hematology abnormality of potential clinical importance is reported.

  10. Number of Participants With Abnormal Urinalysis Dipstick Results-Part A

    Time frame: 8 hours, 24 hours, 48 hours and 72 hours in Periods 1, 2 and 3

    Urine samples were taken for the assessment of following urine parameters: glucose, ketones, occult blood (OB) and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+ indicating proportional concentrations in the urine sample.

  11. Number of Participants With Urinalysis Dipstick Results for Potential of Hydrogen (pH)-Part A

    Time frame: 8 hours, 24 hours, 48 hours and 72 hours in Periods 1, 2 and 3

    Urine samples were taken for the assessment of urine 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 acid pH (5.0 to 6.0). Dipstick test results for pH were presented as number of participants having pH value as 5, 6, 7, 8 or 9.

  12. Number of Participants With Abnormal Urinalysis Dipstick Results-Part B

    Time frame: Day 2 (24 hours); Day 3 (48 hours); Days 4, 13 and 20 (72 hours); pre-dose on Days 7, 10, 11 and 17

    Urine samples were taken for the assessment of following urine parameters: glucose, ketones, OB and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+ indicating proportional concentrations in the urine sample.

  13. Number of Participants With Urinalysis Dipstick Results (pH)-Part B

    Time frame: Day 2 (24 hours); Day 3 (48 hours); Days 4, 13 and 20 (72 hours); pre-dose on Days 7, 10, 11 and 17

    Urine samples were taken for the assessment of urine 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 acid pH (5.0 to 6.0). Dipstick test results for pH were presented as number of participants having pH value as 5, 6, 7, 8 or 9.

  14. Number of Participants With Abnormal Urinalysis Dipstick Results-Part C

    Time frame: 8 hours, 24 hours, 48 hours and 72 hours in Period 1 and Period 2

    Urine samples were taken for the assessment of following urine parameters: glucose, ketones, OB and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+ indicating proportional concentrations in the urine sample.

  15. Number of Participants With Urinalysis Dipstick Results (pH)-Part C

    Time frame: 8 hours, 24 hours, 48 hours and 72 hours in Period 1 and Period 2

    Urine samples were taken for the assessment of urine 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 acid pH (5.0 to 6.0). Dipstick test results for pH were presented as number of participants having pH value as 5, 6, 7, 8 or 9.

  16. Number of Participants With Vital Signs of Potential Clinical Importance-Part A

    Time frame: Up to Day 40

    Vital signs were measured in a supine position after five minutes of rest and included temperature, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate and respiratory rate. The clinical concern range for the parameters included: SBP (low: <85 millimeters of mercury [mmHg] and high: >160 mmHg), DBP (low: <45 mmHg and high: >100 mmHg) and heart rate (low: <40 beats per minute [bpm] and high: >110 bpm). Number of participants with any vital signs of potential clinical importance is reported.

  17. Number of Participants With Vital Signs of Potential Clinical Importance-Part B

    Time frame: Up to Day 34

    Vital signs were measured in a supine position after five minutes of rest and included temperature, SBP, DBP, heart rate and respiratory rate. The clinical concern range for the parameters included: SBP (low: <85 mmHg and high: >160 mmHg), DBP (low: <45 mmHg and high: >100 mmHg) and heart rate (low: <40 bpm and high: >110 bpm). Number of participants with any vital signs of potential clinical importance is reported.

  18. Number of Participants With Vital Signs of Potential Clinical Importance-Part C

    Time frame: Up to Day 29

    Vital signs were measured in a supine position after five minutes of rest and included temperature, SBP, DBP, heart rate and respiratory rate. The clinical concern range for the parameters included: SBP (low: <85 mmHg and high: >160 mmHg), DBP (low: <45 mmHg and high: >100 mmHg) and heart rate (low: <40 bpm and high: >110 bpm). Number of participants with any vital signs of potential clinical importance is reported.

  19. Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Part A

    Time frame: Up to Day 40

    Twelve-lead ECGs were recorded with the participants in a supine position using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and corrected QT (QTc) intervals. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for worst case post-Baseline is presented. Baseline value is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  20. Number of Participants With Abnormal ECG Findings-Part B

    Time frame: Up to Day 34

    Twelve-lead ECGs were recorded with the participants in a supine position using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and QTc intervals. CS and NCS abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for worst case post-Baseline is presented. Baseline value is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  21. Number of Participants With Abnormal ECG Findings-Part C

    Time frame: Up to Day 29

    Twelve-lead ECGs were recorded with the participants in a supine position using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and QTc intervals. CS and NCS abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for worst case post-Baseline is presented. Baseline value is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  22. Area Under Tha Plasma Drug Concentration Versus Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0 to t]) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  23. AUC(0 to t) of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  24. AUC(0 to t) of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  25. AUC(0 to t) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  26. AUC(0 to t) of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)

    Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  27. AUC(0 to t) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)

    Time frame: Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  28. Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0 to Inf]) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  29. AUC(0 to Inf) of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  30. AUC(0 to Inf) of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  31. AUC(0 to Inf) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  32. AUC(0 to Inf) of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)

    Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  33. AUC(0 to Inf) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)

    Time frame: Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  34. Maximum Observed Plasma Concentration (Cmax) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  35. Cmax of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  36. Cmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  37. Cmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  38. Cmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)

    Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  39. Cmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)

    Time frame: Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  40. Time to Maximum Observed Plasma Concentration (Tmax) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  41. Tmax of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  42. Tmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  43. Tmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  44. Tmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)

    Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  45. Tmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)

    Time frame: Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  46. Apparent Terminal Half-life (T1/2) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  47. T1/2 of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  48. T1/2 of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  49. T1/2 of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  50. T1/2 of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)

    Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  51. T1/2 of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)

    Time frame: Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Secondary outcomes

  1. AUC(0 to t) of GSK3439171A (Food Effect)-Part C

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  2. AUC(0 to Inf) of GSK3439171A (Food Effect)-Part C

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  3. Cmax for GSK3439171A (Food Effect)-Part C

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  4. Tmax for GSK3439171A-Part C

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  5. T1/2 for GSK3439171A-Part C

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  6. Dose Proportionality of GSK3439171A Using AUC(0 to t) Following a Single Dose-Part A

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

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

  7. Dose Proportionality of GSK3439171A Using AUC(0 to Inf) Following a Single Dose-Part A

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

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

  8. Dose Proportionality of GSK3439171A Using Cmax Following a Single Dose-Part A

    Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

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

  9. Dose Proportionality of GSK3439171A Using AUC(0 to Tau) Following Repeat Dose-Part B

    Time frame: Days 10 and 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

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

  10. Dose Proportionality of GSK3439171A Using Cmax Following Repeat Dose-Part B

    Time frame: Days 10 and 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

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

  11. Observed Accumulation Ratio for AUC (AUC[Ro])-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Days 1 and 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. AUC(Ro) was calculated as Day17 AUC(0 to tau) divided by Day 1 AUC (0 to tau). Analysis was performed using Mixed effect model with AUC (0 to tau) as the response variable. Treatment, visit and treatment-by-visit interaction are added as fixed effects and participant as random effect. Ratio and 90% confidence interval of the ratio is presented.

  12. Observed Accumulation Ratio for AUC (AUC[Ro])-Part B (GSK3439171A 40 mg Only)

    Time frame: Days 1 and 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. AUC(Ro) was calculated as Day10 AUC(0 to tau) divided by Day 1 AUC (0 to tau). Analysis was performed using Mixed effect model with AUC (0 to tau) as the response variable. Treatment, visit and treatment-by-visit interaction are added as fixed effects and participant as random effect. Ratio and 90% confidence interval of the ratio is presented.

  13. Observed Accumulation Ratio for Cmax (RCmax)-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Days 1 and 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. RCmax was calculated as Day17 Cmax divided by Day 1 Cmax. Analysis was performed using Mixed effect model with Cmax as the response variable. Treatment, visit and treatment-by-visit interaction are added as fixed effects and participant as random effect. Ratio and 90% confidence interval of the ratio is presented.

  14. Observed Accumulation Ratio for Cmax (RCmax)-Part B (GSK3439171A 40 mg Only)

    Time frame: Days 1 and 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. RCmax was calculated as Day10 Cmax divided by Day 1 Cmax. Analysis was performed using Mixed effect model with Cmax as the response variable. Treatment, visit and treatment-by-visit interaction are added as fixed effects and participant as random effect. Ratio and 90% confidence interval of the ratio is presented.

  15. Steady State Accumulation Ratio (Rss)-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: Days 1 and 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Rss was calculated as Day 17 AUC(0-tau) divided by Day 1 AUC(0-inf). Analysis was performed using Mixed Effect Model, with AUC(0-tau) and AUC(0-inf) as the response variables. Treatment, visit, parameter and parameter-by-treatment-by-visit interaction are added as fixed effects and participant as random effect. Ratio and 90% confidence interval of the ratio is presented.

  16. Steady State Accumulation Ratio (Rss)-Part B (GSK3439171A 40 mg Only)

    Time frame: Days 1 and 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Rss was calculated as Day 10 AUC(0-tau) divided by Day 1 AUC(0-inf). Analysis was performed using Mixed Effect Model, with AUC(0-tau) and AUC(0-inf) as the response variables. Treatment, visit, parameter and parameter-by-treatment-by-visit interaction are added as fixed effects and participant as random effect. Ratio and 90% confidence interval of the ratio is presented.

  17. Trough Plasma Concentrations at the End of Dosing Interval for Repeat Doses on Days 6, 7, 9, 10, 11, 15, 16 and 17-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: pre-dose on Days 6, 7, 9, 10, 11, 15, 16 and 17

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  18. Trough Plasma Concentrations at the End of Dosing Interval for Repeat Doses on Days 6, 7, 9 and 10-Part B (GSK3439171A 40 mg Only)

    Time frame: pre-dose on Days 6, 7, 9 and 10

    Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  19. Steady State Assessment Using Trough Plasma Concentration at the End of Dosing Interval for Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)

    Time frame: pre-dose on Days 6, 7, 9, 10, 11, 15, 16 and 17

    Blood samples were collected at indicated time points for pharmacokinetic analysis. The slope estimate of the day effect was obtained from Mixed Effect Model, with visit as the fixed effect and participant as random effect. The analysis was done separately for each treatment. "Variance Component" covariance structure was used. The back transformed slope and 90% confidence interval for the slope is presented.

  20. Steady State Assessment Using Trough Plasma Concentration at the End of Dosing Interval for Repeat Dose-Part B (GSK3439171A 40 mg Only)

    Time frame: pre-dose on Days 6, 7, 9 and 10

    Blood samples were collected at indicated time points for pharmacokinetic analysis. The slope estimate of the day effect was obtained from Mixed Effect Model, with visit as the fixed effect and participant as random effect. The analysis was done separately for each treatment. "Variance Component" covariance structure is used. The back transformed slope and 90% confidence interval for the slope is presented.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

A Three-Part FTIH Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Oral Doses of GSK3439171A, in a Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled, Dose Escalation Study and to Evaluate the Effect of Food on a Single Oral Dose of GSK3439171A in Healthy Adult Participants

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Aug 13, 2018
Registry last updated
Jul 10, 2020

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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