A Study to Evaluate VH4524184 Tablet Absorption, Effects of Food, and Interactions With Other Drugs in Healthy Adults
- Conditions
- HIV Infections
- Interventions
- Registration Number
- NCT07066722
- Lead Sponsor
- ViiV Healthcare
- Brief Summary
The aim of the study is to gather information on how the drug behaves in healthy adults, how it is absorbed, and how it interacts when taken with other medicines.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 124
1. Participants must be 18 to 60 years of age inclusive at the time of signing the Informed consent form (ICF).
2. Male or female
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Male Participants: No restrictions for male participants
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A female participant (female sex assigned at birth) is eligible to participate if she is not pregnant, or breastfeeding and the following condition applies: She is a woman of nonchildbearing potential (WONCBP).
3. Participants who are overtly healthy as determined by medical evaluation 4. AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) 6. Capable of giving signed informed consent.
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History or presence of clinical conditions affecting drug absorption, metabolism, or elimination., 2. Pre-existing clinically relevant, gastro-intestinal pathology 3. Abnormal glucose metabolism requiring insulin or medications. 4. Abnormal blood pressure. 5. History of Lymphoma, leukemia, or any malignancy within the past 5 years (3 years for resected basal or squamous epithelial carcinomas of skin). 6. Breast cancer within the past 10 years. 7. Current or chronic history of liver disease or known hepatic or biliary abnormalities. 8. Medical history of cardiac arrhythmias or cardiac disease or a family long QT syndrome. 9. History of seizure(s) and / or other neurological conditions. 10. Pre-existing psychiatric condition, including depression, anxiety, and/or insomnia/sleep disturbances and / or suicidal ideation. 11. History of drug hypersensitivity.
13. Use of medications/supplements affecting cytochrome P450 enzymes within 7 to 14 days prior to dosing.
14. Contraindications based on selected drug prescribing information. 15. Exposure to more than 4 new investigational products within 12 months 16. Current enrollment or past participation in another investigational study in which an investigational intervention was administered within the last 30 days.
17. Estimated glomelular filtration rate (eGFR) < 90 mL/min or serum creatinine >1.1×ULN [Inker, 2021].
18. Hemoglobin <12.5 g/dL for men and <11 g/dL for women. 19. Presence of Hepatitis B surface antigen (HBsAg) [and Hepatitis B core antibody (HBcAb)] at screening 20. Positive Hepatitis C antibody test result at screening AND positive on reflex to Hepatitis C RNA 21. Positive SARS-CoV-2 test, having signs and symptoms which in the opinion of the investigator are suggestive of COVID-19.
22.Positive pre- study drug/alcohol screen. 23. Poor metabolizers of CYP2C9 and / or CYP2C19 as assessed by genotype testing. HLA-B*1502 positive as applicable to specified cohort.
Other exclusion criteria 24. Regular alcohol consumption exceeding specified limits. 25. Regular use of known drugs of abuse. 26. Nicotine use within 6 months. 27. Sensitivity or allergy to the study drug. 28. ALT >1.5×ULN. 29. Total bilirubin >1.5×ULN. 30. Significant arrhythmias or ECG findings that may compromise participant safety according to the investigator or VH Medical Monitor's assessment.
31. For eligibility determination, triplicate ECGs are required. The criteria are:
- Heart Rate: Excludes males with <45 or >100 bpm, females with <50 or >100 bpm.
- PR Interval: Excludes any PR intervals <120 or >220 msec.
- QRS Duration: Excludes durations <70 or >120 msec.
- QTcF Interval: Excludes intervals >450 msec.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part 1A_VH4524184 (Sequence 1) VH4524184 Participants will receive VH4524184 tablet(s) of Dose level 1 followed by Dose level 2 in fasted condition. Part 1B_VH4524184 (Sequence 5) VH4524184 Participants will receive VH4524184 tablet of Dose level 2 in fasted condition and then followed by intake of a high fat meal. Part 2_Cohort 1 VH4524184 Participants will receive VH4524184 tablet and Itraconazole. Part 2_Cohort 1 Itraconazole Participants will receive VH4524184 tablet and Itraconazole. Part 2_Cohort 2A VH4524184 Participants will receive VH4524184 and Rifabutin. Part 2_Cohort 2A Rifabutin Participants will receive VH4524184 and Rifabutin. Part 1A_VH4524184 (Sequence 2) VH4524184 Participants will receive VH4524184 tablet(s) of Dose level 2 followed by Dose level 1 in fasted condition. Part 1A_VH4524184 (Sequence 3) VH4524184 Participants will receive VH4524184 tablet(s) of Dose level 3 followed by Dose level 2 in fasted condition. Part 1B_VH4524184 Sequence 6) VH4524184 Participants will receive VH4524184 tablet of Dose level 2 following a high fat meal and then in fasted condition. Part 1B_VH4524184 (Sequence 7) VH4524184 Participants will receive VH4524184 tablet of Dose level 3 in fasted condition and then followed by intake of a high fat meal. Part 1B_VH4524184 (Sequence 8) VH4524184 Participants will receive VH4524184 tablet of Dose level 3 following a high fat meal and then in a fasted condition. Part 1A_VH4524184 (Sequence 4) VH4524184 Participants will receive VH4524184 tablet(s) of Dose level 2 followed by Dose level 3 in fasted condition. Part 2_Cohort 2B VH4524184 Participants will receive VH4524184 tablet and Phenytoin. Part 2_Cohort 2B Phenytoin Participants will receive VH4524184 tablet and Phenytoin. Part 2_ Cohort 3 VH4524184 Participants will receive Metformin and VH4524184 tablets. Part 2_ Cohort 3 Metformin Participants will receive Metformin and VH4524184 tablets.
- Primary Outcome Measures
Name Time Method Part 1: Maximum plasma concentration (Cmax) for VH4524184 Up to Day 18 Part 1: Area under the concentration-time curve from 0 to tau (AUC0-t) for VH4524184 Up to day 18 Part 1: Area under the concentration-time curve from 0 to infinity (AUC0-inf) for VH4524184 Up to day 18 Part 2: Cmax for VH4524184 At Day 1, Day 14, Day 19 and Day 22 Part 2: AUC0-t of VH4524184 At Day 1, Day 14, Day 19 and Day 22 Part 2: AUC0-inf of VH4524184 At Day 1, Day 14, Day 19 and Day 22 Part 2: Cmax for metformin At Day 5 and Day 16 Part 2: AUC0-t for metformin At Day 5 and Day 16
- Secondary Outcome Measures
Name Time Method Number of participants with adverse events (AEs) and severity of AEs From Day 1 up to Day 42 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. Severity of grades are defined as Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Potentially Life- Threatening.
Number of participants with AEs leading to discontinuation of study intervention Throughout the study treatment period (from Day 1 up to Day 33) Number of participants with Change in laboratory parameters From Day 1 up to Day 42 Number of participants with maximum toxicity grade increase from baseline in laboratory parameters From Day 1 up to Day 42 Toxicity is graded using the DAIDS criteria Version 2.1 where grades were defined based on numeric criteria as follows Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: potentially life-threatening. A higher grade indicates greater severity.
Time to maximum concentration (Tmax) of VH4524184 At Day 1, Day 14, Day 19 and Day 22 Apparent Terminal Half Life (T1/2) of VH4524184 At Day 1, Day 14, Day 19 and Day 22 Apparent oral clearance (CL/F) of VH4524184 At Day 1, Day 14, Day 19 and Day 22
Related Research Topics
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Trial Locations
- Locations (1)
GSK Investigational Site
🇺🇸Salt Lake City, Utah, United States
GSK Investigational Site🇺🇸Salt Lake City, Utah, United StatesUS GSK Clinical Trials Call CenterContact877-379-3718GSKClinicalSupportHD@gsk.comEU GSK Clinical Trials Call CentreContact+44 (0) 20 8990 4466GSKClinicalSupportHD@gsk.comPatrick YaoPrincipal InvestigatorAhad SabetPrincipal Investigator