Phase 1
Completed N=16
A Two-part Study to Compare a Tablet and Capsule Formulation of GSK2838232 With and Without Food, and to Assess the Safety and Drug Levels of Repeated Once-daily Doses of GSK2838232 Without Ritonavir
Infection, Human Immunodeficiency Virus · HIV
Source: ClinicalTrials.gov NCT03234036 ↗
Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Mar 2019
Primary outcomePrimary: Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State — 4672.28; 4437.98 Hours*nanogram per milliliter
Summary
This study will be conducted in two Parts to confirm the acceptability/selection of a tablet formulation for future clinical development of GSK2838232. Part 1 of the study will assess single ritonavir (RTV)-boosted doses of a new tablet formulation given with food (containing approximately 30% fat) against the reference capsule formulation also given with food and then will assess the impact of fasted conditions on the tablet performance. In Part 2, non-boosted GSK2838232 will be given as once-daily tablet doses for 11 days in a separate group of subjects, assuming the tablet performance is considered acceptable from Part 1. Approximately 16 healthy subjects will be enrolled to provide at least 12 evaluable subjects through the three study periods in Part 1. 10 healthy subjects will be enrolled to provide at least 8 evaluable subjects through the single study period in Part 2. The maximum duration of study participation will be approximately 9 to 10 weeks for Part 1; and 8 to 9 weeks for Part 2.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State |
4672.28; 4437.98 | — |
| PRIMARY Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State |
109.054; 118.118 | — |
| PRIMARY Part 1: AUC (0-infinity) Following Administration of GSK2838232 Tablet in Fasted and Fed State |
4437.98; 1816.27 | — |
| PRIMARY Part 1: Cmax Following Administration of GSK2838232 Tablet in Fasted and Fed State |
118.118; 50.437 | — |
| PRIMARY Part 1: Time of Occurrence of Cmax (Tmax) Following Administration of GSK2838232 Tablet in Fasted and Fed State |
5.983; 3.508 | — |
| PRIMARY Part 2: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs |
0; 0; 1; 0 | — |
| PRIMARY Part 2: Number of Participants With Worst Case Hematology Results to Potential Clinical Importance (PCI) Criteria |
0; 0; 3; 7; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria |
0; 0; 3; 7; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria |
0; 0; 3; 7; 0; 0 | — |
| PRIMARY Part 2: Blood Pressure at Indicated Time Points |
73.667; 73.143; 65.443; 72.333; 54.667; 64.714 | — |
| PRIMARY Part 2: Change From Baseline in Blood Pressure |
-10.777; -7.619; -3.443; -8.619; 8.223; 1.381 | — |
| PRIMARY Part 2: Pulse Rate at Indicated Time Points |
63.667; 64.143; 63.663; 63.714; 68.000; 72.286 | — |
| PRIMARY Part 2: Change From Baseline in Pulse Rate |
4.337; 8.571; 1.003; 2.286; -5.997; -5.429 | — |
| PRIMARY Part 2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings |
2; 6; 0; 0; 2; 4 | — |
| PRIMARY Part 2: Change From Baseline in Mean Heart Rate Values as ECG Parameter |
4.000; 10.240; 2.000; 1.954; -6.000; 0.526 | — |
| PRIMARY Part 2: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters |
-7.110; -3.999; -6.443; -12.284; -0.443; 3.430 | — |
| PRIMARY Part 2: Area Under the Plasma Drug Concentration Time Curve From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State |
895.42; 1184.55 | — |
| PRIMARY Part 2: Cmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State |
79.575; 94.239 | — |
| PRIMARY Part 2: Observed Concentration at the End of the Dosing Interval (Ctau) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State |
21.620; 27.668 | — |
| PRIMARY Part 2: Tmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State |
4.000; 3.500 | — |
| PRIMARY Part 2: Lag-time (Tlag) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 1 |
0.500 | — |
| PRIMARY Part 2: AUC(0-infinity) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11 |
1816.34 | — |
| PRIMARY Part 2: Apparent Terminal Phase Half-life (T1/2) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11 |
23.217 | — |
| PRIMARY Part 2: Time of Last Quantifiable Concentration (Tlast) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11 |
118.800 | — |
| SECONDARY Part 1: Number of Participants With SAEs and Non-SAEs |
0; 0; 0; 3; 2; 1 | — |
| SECONDARY Part 1: Number of Participants With Worst Case Hematology Results to PCI Criteria |
0; 0; 0; 15; 15; 14 | — |
| SECONDARY Part 1: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria |
0; 0; 0; 15; 15; 14 | — |
| SECONDARY Part 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria |
0; 0; 0; 15; 15; 14 | — |
| SECONDARY Part 1: Blood Pressure at Indicated Time Points |
68.667; 69.533; 65.000; 67.467; 68.467; 65.643 | — |
| SECONDARY Part 1: Change From Baseline in Blood Pressure |
-2.756; -2.112; 0.429; -3.823; -3.712; -0.857 | — |
| SECONDARY Part 1: Pulse Rate at Indicated Time Points |
64.067; 62.333; 60.214; 62.333; 63.067; 59.071 | — |
| SECONDARY Part 1: Change From Baseline in Pulse Rate |
9.644; 8.023; -1.286; 7.644; 8.623; 0.357 | — |
| SECONDARY Part 1: Number of Participants With Abnormal ECG Findings |
10; 9; 9; 0; 0; 0 | — |
| SECONDARY Part 1: Change From Baseline in Mean Heart Rate Values as ECG Parameter |
11.623; 7.955; -0.642; 10.623; 8.489; -1.230 | — |
| SECONDARY Part 1: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters |
-4.667; -3.067; -3.000; -6.001; -8.000; -1.846 | — |
| SECONDARY Part 1: Tlag Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State |
1.000; 1.000; 0.500 | — |
| SECONDARY Part 1: Tmax Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State |
11.967; 5.983; 3.508 | — |
| SECONDARY Part 1: T1/2 Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State |
15.606; 15.692; 17.061 | — |
| SECONDARY Part 1: Tlast Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State |
119.983; 119.983; 120.017 | — |
| SECONDARY Part 1: Plasma Drug Concentration at 24 Hours (C24) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State |
84.536; 75.643; 26.852 | — |
| SECONDARY Part 1: AUC(0-t) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State |
4595.35; 4371.47; 1776.21 | — |
| SECONDARY Part 2: Slope of Pre-dose Concentration of GSK2838232 Administered as Non-boosted Once-daily Doses of a Tablet Formulation to Assess Achievement of Steady State |
-0.00910; -0.0150; -0.0379; -0.0490; -0.0679; -0.0672 | — |
| SECONDARY Part 2: Accumulation Ratio Calculated From AUC(0-tau) Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation |
1.3340 | — |
| SECONDARY Part 2: Accumulation Ratio Calculated From Cmax Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation |
1.2118 | — |
| SECONDARY Part 2: Accumulation Ratio Calculated From Ctau Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation |
1.3205 | — |
Eligibility Criteria
Inclusion Criteria
- Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, and 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.
- A creatinine clearance (CLcr) > 80 milliliter per minute (mL/min) as determined by Cockcroft-Gault equation: CLcr = (140 minus age) multiplied by weight divided by (72 multiplied by serum creatinine) (times 0.85 if female) where age is in years, weight in kilogram (kg), and serum creatinine is in units of milligram per deciliter (mg/dL).
- Body weight >=50.0 kg (110 pounds [lbs.]) for men and >=45.0 kg (99 lbs) for women and body mass index (BMI) within the range 18.5 to 31.0 kg/meter (m)^2 (inclusive).
- Males or females.
- A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and of non-reproductive potential which is defined as:
Reproductive potential:
There is no definitive drug-drug interaction (DDI) information with GSK2838232 and an interaction with oral contraceptives is possible, so other (barrier, inter-uterine device etc.) methods of contraception will be required. Females of reproductive potential may only be enrolled if they are using two forms of complementary contraception, which must include at least one barrier method. They will be counseled on safer sex practices. Fertile females, who have an established, long-term lifestyle of sexual abstinence, or only same sex partners, require no other means of birth control.
Non-reproductive potential:
- Pre-menopausal females with one of the following: Documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented Bilateral Oophorectomy.
- Postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
- Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until one week after the last dose of study medication.
- Vasectomy with documentation of azoospermia.
- Male condom plus partner use of one of the contraceptive options below: Contraceptive subdermal implant with a 1.5 times upper limit of normal (ULN)
- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin 14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- Regular use of tobacco- or nicotine- containing products within 6 months prior to screening. Unable to refrain from smoking from the Screening Visit through the last blood sample collected. As confirmed by a urine cotinine test.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
- Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C virus (HCV)
Data sourced from ClinicalTrials.gov (NCT03234036). 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.