Phase 1
Completed N=18
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
Source: ClinicalTrials.gov NCT03627494 ↗Enrolled (actual)
18
Serious AEs
0.0%
Results posted
Jul 2020
Primary outcomePrimary: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A — 1; 0; 2; 2 Participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A |
1; 0; 2; 2; 2; 1 | — |
| PRIMARY Number of Participants With AEs and SAEs-Part B |
4; 5; 8; 3; 0; 0 | — |
| PRIMARY Number of Participants With AEs and SAEs-Part C |
1; 3; 0; 0 | — |
| PRIMARY Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance-Part A |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance-Part B |
0; 0; 0; 1 | — |
| PRIMARY Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance-Part C |
0; 0 | — |
| PRIMARY Number of Participants With Hematology Abnormalities of Potential Clinical Importance-Part A |
2; 0; 1; 0; 1; 1 | — |
| PRIMARY Number of Participants With Hematology Abnormalities of Potential Clinical Importance-Part B |
3; 3; 2; 1 | — |
| PRIMARY Number of Participants With Hematology Abnormalities of Potential Clinical Importance-Part C |
5; 3 | — |
| PRIMARY Number of Participants With Abnormal Urinalysis Dipstick Results-Part A |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Urinalysis Dipstick Results for Potential of Hydrogen (pH)-Part A |
0; 0; 0; 1; 1; 3 | — |
| PRIMARY Number of Participants With Abnormal Urinalysis Dipstick Results-Part B |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Urinalysis Dipstick Results (pH)-Part B |
1; 2; 1; 1; 4; 5 | — |
| PRIMARY Number of Participants With Abnormal Urinalysis Dipstick Results-Part C |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Urinalysis Dipstick Results (pH)-Part C |
0; 1; 1; 1; 3; 4 | — |
| PRIMARY Number of Participants With Vital Signs of Potential Clinical Importance-Part A |
0; 1; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Vital Signs of Potential Clinical Importance-Part B |
0; 0; 0; 2 | — |
| PRIMARY Number of Participants With Vital Signs of Potential Clinical Importance-Part C |
1; 0 | — |
| PRIMARY Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Part A |
16; 5; 6; 5; 4; 6 | — |
| PRIMARY Number of Participants With Abnormal ECG Findings-Part B |
9; 9; 8; 9; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal ECG Findings-Part C |
10; 11; 0; 0 | — |
| PRIMARY 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) |
1180.6 | — |
| PRIMARY AUC(0 to t) of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg) |
2268.6; 9289.4; 17052.3; 35822.0; 46086.3 | — |
| PRIMARY AUC(0 to t) of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg) |
1474.0; 2299.2 | — |
| PRIMARY AUC(0 to t) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg) |
2072.8; 3628.1 | — |
| PRIMARY AUC(0 to t) of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only) |
10031.8 | — |
| PRIMARY AUC(0 to t) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only) |
14896.5 | — |
| PRIMARY 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) |
1247.2 | — |
| PRIMARY AUC(0 to Inf) of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg) |
2305.3; 9441.8; 17257.9; 36478.0; 46844.6 | — |
| PRIMARY AUC(0 to Inf) of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg) |
1514.9; 2345.6 | — |
| PRIMARY AUC(0 to Inf) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg) |
2129.0; 3687.1 | — |
| PRIMARY AUC(0 to Inf) of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only) |
10182.6 | — |
| PRIMARY AUC(0 to Inf) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only) |
15098.7 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only) |
111.01 | — |
| PRIMARY Cmax of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg) |
214.03; 635.37; 1272.26; 2132.49; 2938.01 | — |
| PRIMARY Cmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg) |
117.40; 192.62 | — |
| PRIMARY Cmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg) |
138.08; 243.98 | — |
| PRIMARY Cmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only) |
682.62 | — |
| PRIMARY Cmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only) |
1016.29 | — |
| PRIMARY Time to Maximum Observed Plasma Concentration (Tmax) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only) |
1.0000 | — |
| PRIMARY Tmax of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg) |
0.9830; 1.5000; 1.7415; 4.0000; 2.9915 | — |
| PRIMARY Tmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg) |
1.5000; 2.0000 | — |
| PRIMARY Tmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg) |
3.0000; 2.0000 | — |
| PRIMARY Tmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only) |
4.0000 | — |
| PRIMARY Tmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only) |
3.0000 | — |
| PRIMARY Apparent Terminal Half-life (T1/2) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only) |
9.847 | — |
| PRIMARY T1/2 of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg) |
11.233; 11.956; 11.183; 11.761; 11.076 | — |
| PRIMARY T1/2 of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg) |
15.348; 14.275 | — |
| PRIMARY T1/2 of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg) |
13.253; 11.584 | — |
| PRIMARY T1/2 of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only) |
11.908 | — |
| PRIMARY T1/2 of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only) |
10.948 | — |
| SECONDARY AUC(0 to t) of GSK3439171A (Food Effect)-Part C |
16263.2; 14770.1 | — |
| SECONDARY AUC(0 to Inf) of GSK3439171A (Food Effect)-Part C |
16458.9; 14995.0 | — |
| SECONDARY Cmax for GSK3439171A (Food Effect)-Part C |
1155.60; 1025.45 | — |
| SECONDARY Tmax for GSK3439171A-Part C |
3.0000; 4.0000 | — |
| SECONDARY T1/2 for GSK3439171A-Part C |
10.820; 11.679 | — |
| SECONDARY Dose Proportionality of GSK3439171A Using AUC(0 to t) Following a Single Dose-Part A |
1.068 | — |
| SECONDARY Dose Proportionality of GSK3439171A Using AUC(0 to Inf) Following a Single Dose-Part A |
1.057 | — |
| SECONDARY Dose Proportionality of GSK3439171A Using Cmax Following a Single Dose-Part A |
0.944 | — |
| SECONDARY Dose Proportionality of GSK3439171A Using AUC(0 to Tau) Following Repeat Dose-Part B |
0.966 | — |
| SECONDARY Dose Proportionality of GSK3439171A Using Cmax Following Repeat Dose-Part B |
0.972 | — |
| SECONDARY Observed Accumulation Ratio for AUC (AUC[Ro])-Part B (GSK3439171A 5 mg and 11 mg) |
1.39; 1.52 | — |
| SECONDARY Observed Accumulation Ratio for AUC (AUC[Ro])-Part B (GSK3439171A 40 mg Only) |
1.49 | — |
| SECONDARY Observed Accumulation Ratio for Cmax (RCmax)-Part B (GSK3439171A 5 mg and 11 mg) |
1.18; 1.28 | — |
| SECONDARY Observed Accumulation Ratio for Cmax (RCmax)-Part B (GSK3439171A 40 mg Only) |
1.49 | — |
| SECONDARY Steady State Accumulation Ratio (Rss)-Part B (GSK3439171A 5 mg and 11 mg) |
1.07; 1.21 | — |
| SECONDARY Steady State Accumulation Ratio (Rss)-Part B (GSK3439171A 40 mg Only) |
1.16 | — |
| SECONDARY 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) |
27.3206; 35.6842; 29.5449; 41.6334; 28.5910; 38.2703 | — |
| SECONDARY 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) |
184.1428; 209.1741; 211.2785; 215.1369 | — |
| SECONDARY Steady State Assessment Using Trough Plasma Concentration at the End of Dosing Interval for Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg) |
1.000; 0.997 | — |
| SECONDARY Steady State Assessment Using Trough Plasma Concentration at the End of Dosing Interval for Repeat Dose-Part B (GSK3439171A 40 mg Only) |
1.003 | — |
Eligibility Criteria
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 1.5 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 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 interventi
Data sourced from ClinicalTrials.gov (NCT03627494). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.