Phase 1
Completed N=8
Safety, Tolerability and Pharmacokinetic Investigation of GSK3882347 in Healthy Participants.
Source: ClinicalTrials.gov NCT04488770 ↗Enrolled (actual)
8
Serious AEs
0.0%
Results posted
Feb 2023
Primary outcomePrimary: Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) — 7; 1; 2; 2 Participants
Summary
This is a phase 1, 2-part, double-blind (sponsor-unblinded), randomized, placebo-controlled, first time in human (FTIH) study, that includes both single-ascending and multiple-ascending dose phase to assess the safety, tolerability, and pharmacokinetics (PK) of GSK3882347 in healthy adult men and Woman of Non Childbearing Potential (WONCBP). Part 1 will be the single ascending dose (SAD) phase and Part 2 will be the multiple ascending dose (MAD) phase. Each participant in the SAD cohort will receive a single dose of GSK3882347 or placebo (PBO) in 3:1 ratio and in Part 2 (MAD), participants will be randomized in a 4:1 ratio to receive active treatment and placebo. Part 1 will consist of two cohorts with a maximum of four-period for each cohort, the food effect evaluation will be conducted in last period (Period 4) in only one of the cohorts based on the observed human pharmacokinetics (PK). Part 2 will consist of maximum of four cohorts for each of the MAD dose or placebo.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) |
7; 1; 2; 2; 3; 2 | — |
| PRIMARY Part 2: Number of Participants With Non-serious AEs and SAEs |
5; 4; 2; 7; 7; 0 | — |
| PRIMARY Part 1: Number of Participants With Treatment Related AEs |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Treatment Related AEs |
1; 2; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
2; 2; 0; 0; 1; 1 | — |
| PRIMARY Part 2: Number of Participants With Worst-case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline |
2; 2; 1; 0; 1; 6 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Worst-case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline |
0; 0; 0; 0; 0; 8 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Urinalysis Results Post Baseline Relative to Baseline |
14; 6; 6; 6; 6; 6 | — |
| PRIMARY Part 2: Number of Participants With Worst Case Urinalysis Results Post Baseline Relative to Baseline |
8; 8; 7; 8; 8; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Vital Signs Results Relative to PCI Criteria Post Baseline Relative to Baseline |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Worst Case Vital Signs Results Relative to PCI Criteria Post Baseline Relative to Baseline |
0; 0; 0; 0; 0; 8 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Results Post Baseline Relative to Baseline |
3; 1; 1; 0; 0; 2 | — |
| PRIMARY Part 2: Number of Participants With Worst Case Abnormal ECG Results Post Baseline Relative to Baseline |
3; 3; 6; 6; 3; 0 | — |
| PRIMARY Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) After Single Dose Administration of GSK3882347 |
1671.7; 6514.1; 17717.9; 28472.2; 21456.4; 48381.2 | — |
| PRIMARY Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3882347 |
1954.3; 8249.8; 22266.9; 36561.0; 29091.9; 63052.2 | — |
| PRIMARY Part 1: Area Under the Concentration-time Curve Extrapolated From Time Zero to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3882347 |
2167.0; 8425.5; 22433.7; 36768.0; 29316.1; 63377.3 | — |
| PRIMARY Part 1: Maximum Plasma Concentration (Cmax) After Single Dose Administration of GSK3882347 |
165.7; 661.7; 1825.8; 3126.7; 1834.5; 4671.3 | — |
| PRIMARY Part 1: Plasma Concentrations at 24 Hours (C24h) After Single Dose Administration of GSK3882347 |
27.32; 106.70; 283.18; 500.35; 453.82; 853.98 | — |
| PRIMARY Part 1: Time to Cmax (Tmax) After Single Dose Administration of GSK3882347 |
3.000; 4.000; 4.000; 4.000; 4.000; 4.000 | — |
| PRIMARY Part 1: Lag Time for Absorption (Tlag) After Single Dose Administration of GSK3882347 |
0.375; 0.250; 0.250; 0.250; 0.250; 0.250 | — |
| PRIMARY Part 1: Terminal Elimination Half-life (T1/2) After Single Dose Administration of GSK3882347 |
11.407; 12.269; 11.538; 12.277; 12.984; 12.630 | — |
| PRIMARY Part 2: Area Under the Concentration-time Curve Over the Dosing Interval Tau (AUC[0-tau]) After Repeat Dose Administration of GSK3882347 |
5862.9; 20191.4; 45400.0; 53753.9; 6144.9; 21109.5 | — |
| PRIMARY Part 2: Cmax After Repeat Dose Administration of GSK3882347 |
586.0; 2179.1; 4409.4; 4933.1; 600.4; 2007.4 | — |
| PRIMARY Part 2: Tmax After Repeat Dose Administration of GSK3882347 |
4.000; 3.000; 4.000; 4.008; 4.000; 4.000 | — |
| PRIMARY Part 2: Plasma Concentrations Over the Dosing Interval (Ctau) After Repeat Dose Administration of GSK3882347 |
90.98; 292.53; 789.85; 1084.55; 109.28; 368.34 | — |
| PRIMARY Part 1: Urine Concentration Between 22-24 Hours (C22-24) After Single Dose Administration of GSK3882347 |
1.55; 2.99; 11.27; 15.26; 11.42; 48.54 | — |
| PRIMARY Part 2: Urine Concentration Between 22-24 Hours (C22-24) After Repeat Dose Administration of GSK3882347 |
2.95; 11.98; 18.15; 38.43; 2.56; 16.50 | — |
| PRIMARY Part 1: Amount of Drug Excreted in Urine of Unchanged Drug (Ae Total) After Single Dose Administration of GSK3882347 |
11.16; 32.01; 106.86; 146.43; 95.17; 306.93 | — |
| PRIMARY Part 2: Amount of Drug Excreted in Urine of Unchanged Drug (Ae Total) After Repeat Dose Administration of GSK3882347 |
24.77; 88.30; 188.49; 267.16; 26.71; 108.20 | — |
| PRIMARY Part 1: Percentage of the Given Dose of Drug Excreted in Urine (%fe Total) After Single Dose Administration of GSK3882347 |
74.43; 64.02; 71.24; 58.57; 38.07; 61.39 | — |
| PRIMARY Part 2: Percentage of the Given Dose of Drug Excreted in Urine (%fe Total) After Single Dose Administration of GSK3882347 |
49.54; 58.87; 37.70; 29.68; 53.42; 72.13 | — |
| PRIMARY Part 1: Renal Clearance of Drug (CLr) After Single Dose Administration of GSK3882347 |
5.71; 3.88; 4.80; 4.00; 3.27; 4.87 | — |
| PRIMARY Part 2: Renal Clearance of Drug (CLr) After Repeat Dose Administration of GSK3882347 |
4.24; 4.38; 4.16; 4.98; 4.34; 5.12 | — |
| SECONDARY Part 1: Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) After Single Dose Administration of GSK3882347 |
1181.6; 4609.1; 12519.7; 20127.1; 14009.0; 33030.8 | — |
| SECONDARY Part 1: Plasma Concentrations at 12 Hours (C12) After Single Dose Administration of GSK3882347 |
58.73; 232.96; 636.41; 947.62; 857.73; 1806.50 | — |
| SECONDARY Part 1: Apparent Oral Clearance (CL/F) After Single Dose Administration of GSK3882347 |
6.92; 5.93; 6.69; 6.80; 8.53; 7.89 | — |
| SECONDARY Part 1: Apparent Volume of Distribution After Oral Administration (Vz/F) After Single Dose Administration of GSK3882347 |
113.92; 105.04; 111.30; 120.43; 159.74; 143.76 | — |
| SECONDARY Part 1: Mean Residence Time (MRT) After Single Dose Administration of GSK3882347 |
15.775; 16.843; 15.614; 16.262; 18.818; 17.259 | — |
| SECONDARY Part 2: Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) After Repeat Dose Administration of GSK3882347 |
4076.3; 14411.9; 30660.3; 35231.6; 4222.8; 14506.3 | — |
| SECONDARY Part 2: Plasma Concentrations at 12 Hours (C12) After Repeat Dose Administration of GSK3882347 |
214.4; 709.1; 1704.8; 2068.2; 221.5; 776.1 | — |
| SECONDARY Part 1: Dose Proportionality of GSK3882347 for Dose Levels 15 mg to 900 mg Using AUC(0-infinity) After Single Dose Administration of GSK3882347 Under Fasted Condition |
0.919 | — |
| SECONDARY Part 1: Dose Proportionality of GSK3882347 for Dose Levels 15 mg to 900 mg Using Cmax After Single Dose Administration of GSK3882347 Under Fasted Condition |
0.903 | — |
| SECONDARY Part 2: Dose Proportionality of GSK3882347 for Dose Levels 50 mg to 900 mg Using AUC(0-tau) After Repeat Dose Administration of GSK3882347 |
0.770; 0.908 | — |
| SECONDARY Part 2: Dose Proportionality of GSK3882347 for Dose Levels 50 mg to 900 mg Using Cmax After Repeat Dose Administration of GSK3882347 |
0.736; 0.841 | — |
| SECONDARY Part 2: Observed Accumulation Ratio (Ro) Using AUC(0-tau) After Repeat Dose Administration of GSK3882347 |
1.05; 1.05; 1.35; 1.53 | — |
| SECONDARY Part 2: Time Invariance of GSK3882347 |
0.83; 0.87; 1.07; 1.13 | — |
| SECONDARY Part 2: Pre-dose Plasma Concentrations After Repeat Dose Administration of GSK3882347 From Days 3 to 7 |
99.48; 326.89; 1157.589; 1578.14; 96.66; 344.56 | — |
| SECONDARY Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect |
28472.2; 21456.4 | — |
| SECONDARY Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC [0-t]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect |
36561.0; 29091.9 | — |
| SECONDARY Part 1: Area Under the Concentration-time Curve Extrapolated From Time Zero to Infinity (AUC [0-infinity]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect |
36768.0; 29316.1 | — |
| SECONDARY Part 1: Maximum Plasma Concentration (Cmax) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect |
3126.7; 1834.5 | — |
| SECONDARY Part 1: Plasma Concentrations at 24 Hours (C24h) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect |
494.7; 449.2 | — |
| SECONDARY Part 1: Tmax After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect |
4.000; 4.000 | — |
| SECONDARY Part 1: Tlag After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect |
0.250; 0.250 | — |
Eligibility Criteria
Inclusion Criteria
- Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A participant 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 (if required), agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Participants with Body weight at least 50.0 kilograms (kg) (110 pound [lbs]) for males and 45.0 kg (99 lbs.) for females; and body mass index (BMI) within the range 18.5 - 32.0 kilograms per meter square (kg/m^2) (inclusive).
- Male and female participants; a female participant is eligible to participate if she is of WONCBP; Male participants are eligible to participate if they agree to the following during the intervention period for at least five days, corresponding to time needed to eliminate study intervention(s) (e.g. 5 terminal half-lives) after the last dose of study intervention), refrain from donating sperm, be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; must agree to use contraception/barrier, agree to use a male condom.
- Capable of giving signed informed consent as described in which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria
- Participants with history or presence of cardiovascular, respiratory, hepatic, urological, 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
- Alanine transaminase (ALT) greater than 1.5 times upper limit of normal (ULN).
- Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin is less than 35%)
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).
- Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
- Male participants with heart rate of less than 45 or greater than 100 beats per minute (bpm), females with less than 50 or greater than 100 bpm.
- Participants with PR interval less than 120 or greater than 220 milliseconds (msec); QRS duration less than 70 msec or greater than 120 msec; QTcF interval greater than 450 msec.
- Evidence of previous myocardial infarction on ECG (does not include ST segment changes associated with re-polarization).
- Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular (AV) block [2nd degree or higher], Wolff-Parkinson-White [WPW] syndrome).
- Sinus Pauses greater than 3 seconds.
- Any significant arrhythmia which, in the opinion of the Investigator or GSK Medical Monitor, will interfere with the safety for the individual participant.
- Non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic beats).
- Current or history of renal disease, or estimated creatinine clearance <90 milliliter (mL)/minute/1.73meter^2 or serum creatinine greater than ULN at screening.
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-
Data sourced from ClinicalTrials.gov (NCT04488770). 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.