Phase 1
N=19
Drug-drug Interaction (DDI) Study of GSK3640254 With Darunavir/Ritonavir (DRV/RTV) and Etravirine (ETR)
HIV Infections
Bottom Line
View on ClinicalTrials.gov: NCT04630002 ↗Enrolled (actual)
19
Serious AEs
0.0%
Results posted
Aug 2023
Primary outcome: Primary: Cohort 1: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3640254 — 27.03; 30.70 Hours*micrograms per milliliter
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- GSK3640254 (Drug); Darunavir/Ritonavir (DRV/RTV) (Drug); Etravirine (ETR) (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- ViiV Healthcare
- Primary completion
- Oct 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cohort 1: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3640254 |
27.03; 30.70 | — |
| PRIMARY Cohort 1: Maximum Observed Concentration (Cmax) of GSK3640254 |
1.752; 1.863 | — |
| PRIMARY Cohort 1: AUC(0-tau) of DRV |
57.47; 53.37 | — |
| PRIMARY Cohort 1: Cmax of DRV |
7.037; 7.268 | — |
| PRIMARY Cohort 1: AUC(0-tau) of RTV |
7.303; 7.790 | — |
| PRIMARY Cohort 1: Cmax of RTV |
1.178; 1.306 | — |
| PRIMARY Cohort 2: AUC(0-tau) of GSK3640254 |
27.86; 14.73 | — |
| PRIMARY Cohort 2: Cmax of GSK3640254 |
1.889; 1.136 | — |
| PRIMARY Cohort 2: AUC(0-tau) of ETR |
8.340; 9.791 | — |
| PRIMARY Cohort 2: Cmax of ETR |
0.9749; 1.102 | — |
| PRIMARY Cohort 3: AUC(0-tau) of GSK3640254 |
24.99; 22.78 | — |
| PRIMARY Cohort 3: Cmax of GSK3640254 |
1.578; 1.383 | — |
| SECONDARY Cohort 1: Plasma Concentration at the End of the Dosing Interval (Ctau) of DRV |
2.957; 2.637 | — |
| SECONDARY Cohort 1: Time of Maximum Observed Concentration (Tmax) of DRV |
3.000; 3.000 | — |
| SECONDARY Cohort 1: Ctau of RTV |
0.3194; 0.3314 | — |
| SECONDARY Cohort 1: Tmax of RTV |
4.000; 4.000 | — |
| SECONDARY Cohort 1: Ctau of GSK3640254 |
0.8152; 0.9530 | — |
| SECONDARY Cohort 1: Tmax of GSK3640254 |
4.000; 4.000 | — |
| SECONDARY Cohort 2: Ctau of ETR |
0.4705; 0.5837 | — |
| SECONDARY Cohort 2: Tmax of ETR |
3.500; 4.000 | — |
| SECONDARY Cohort 2: Ctau of GSK3640254 |
0.7706; 0.3901 | — |
| SECONDARY Cohort 2: Tmax of GSK3640254 |
4.000; 3.000 | — |
| SECONDARY Cohort 1: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs) |
0; 0; 0; 6; 4; 5 | — |
| SECONDARY Cohort 2: Number of Participants With SAEs and Non-SAEs |
0; 0; 0; 3; 4; 7 | — |
| SECONDARY Cohort 3: Number of Participants With SAEs and Non-SAEs |
0; 0; 1; 8 | — |
| SECONDARY Cohort 1: Number of Participants With AEs Leading to Discontinuations and Deaths |
0; 1; 0; 0; 0; 0 | — |
| SECONDARY Cohort 2: Number of Participants With AEs Leading to Discontinuations and Deaths |
0; 0; 1; 0; 0; 0 | — |
| SECONDARY Cohort 3: Number of Participants With AEs Leading to Discontinuations and Deaths |
0; 1; 0; 0 | — |
| SECONDARY Cohort 1: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 2: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 3: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 1: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Bilirubin and Direct Bilirubin |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 1: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Calcium, Creatine Kinase, Creatinine, Phosphate, Potassium and Sodium |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 1: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Glucose, Triglycerides, Lipase, Urate and Cholesterol |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 2: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Bilirubin and Direct Bilirubin |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 2: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Calcium, Creatine Kinase, Creatinine, Phosphate, Potassium and Sodium |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 2: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Glucose, Triglycerides, Lipase, Urate and Cholesterol |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 3: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Bilirubin and Direct Bilirubin |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 3: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Calcium, Creatine Kinase, Creatinine, Phosphate, Potassium and Sodium |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 3: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Glucose, Triglycerides, Lipase, Urate and Cholesterol |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 1: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Urinalysis Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 2: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Urinalysis Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 3: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Urinalysis Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 1: Number of Participants With Vital Sign Values of Potential Clinical Importance (PCI) Criteria |
0; 2; 0; 0; 0; 0 | — |
| SECONDARY Cohort 2: Number of Participants With Vital Sign Values of PCI Criteria |
0; 0; 0; 0; 0; 1 | — |
| SECONDARY Cohort 3: Number of Participants With Vital Sign Values of PCI Criteria |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 1: Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 2: Number of Participants With Clinically Significant Abnormal ECG Findings |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohort 3: Number of Participants With Clinically Significant Abnormal ECG Findings |
0; 0; 0; 0; 0; 0 | — |
Summary
This is an open-label, single-sequence, multiple-dose, 3 cohort study to investigate the effects of DRV/RTV and/or ETR on the pharmacokinetics (PK) of GSK3640254 and the effects of GSK3640254 on the PK of DRV/RTV and/or ETR. This study will aid in understanding these interactions and resulting changes in exposure (if any) when given in combination with GSK3640254.
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 investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and screening ECG).
- Body weight more than or equal to (>=)50.0 kilograms (kg) (110 pounds [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 31.0 kilograms per square meter (kg/m^2) (inclusive).
- Male or female participants:
- Male participants should not engage in intercourse while confined in the study site. There is no need for an extended period of double barrier use or prolonged abstinence after study discharge.
- Female participants:
(i) A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a non-hormonal contraceptive method that is highly effective, with a failure rate of less than ( ]6 months) outpatient treatment. Participants with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy ( 1.5 times upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin 100 beats per minute (bpm).
- PR interval >200 milliseconds (ms).
- Corrected QT interval (QTc) >450 ms.
- History of regular alcohol consumption within 6 months of the study, defined as an average weekly intake of >14 units. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
- Unable to refrain from tobacco or nicotine-containing products within 3 months prior to screening.
- 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.
Data sourced from ClinicalTrials.gov (NCT04630002). 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.