HIV Infections
Conditions
Keywords
Drug-drug interaction, First-time in human, HIV, Bioavailability, Healthy Adult Participants
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.
Interventions
DRUGVH4524184
VH4524184 will be administered.
DRUGItraconazole
Itraconazole will be administered.
DRUGRifabutin
Rifabutin will be administered.
DRUGPhenytoin
Extended phenytoin sodium will be administered.
DRUGMetformin
Metformin will be administered.
DRUGDigoxin
Digoxin will be administered.
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
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 1. Male Participants: No restrictions for male participants 2. 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.
Exclusion criteria
1. 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. Clinically significant 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. History of syncope, clinically significant palpitations, cardiac arrhythmias or cardiac disease or a family long QT syndrome. 9. History of seizure(s) and / or other clinically significant 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 1 and Day 15 |
| Part 2: AUC0-t for metformin | At Day 1 and Day 15 |
| Part 2: Cmax for Digoxin | At Day 1 and Day 15 |
| Part 2: AUC0-t for Digoxin | At Day 1 and Day 15 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Part 1: Time to maximum concentration (Tmax) of VH4524184 | At Day 1 | — |
| Part 1: Apparent Terminal Half Life (T1/2) of VH4524184 | At Day 1 | — |
| Part 1: Apparent oral clearance (CL/F) of VH4524184 | At Day 1 | — |
| Part 2: Tmax of VH4524184 Following Single-Dose Administration with CYP3A4 Inhibitors and Inducers (Itraconazole, Rifabutin, Phenytoin) | At Day 1, Day 14, Day 19 and Day 22 | — |
| Part 2: T1/2 of VH4524184 Following Single-Dose Administration with CYP3A4 Inhibitors and Inducers (Itraconazole, Rifabutin, Phenytoin) | At Day 1, Day 14, Day 19 and Day 22 | — |
| Part 2: CL/F of VH4524184 Following Single-Dose Administration with CYP3A4 Inhibitors and Inducers (Itraconazole, Rifabutin, Phenytoin) | At Day 1, Day 14, Day 19 and Day 22 | — |
| Part 2: Cmax for VH5424184 Following Comedication with Transporter Substrates with metformin and digoxin | At Day 1 and Day 15 | — |
| Part 2: AUC0-t for VH5424184 Following Comedication with Transporter Substrates metformin and digoxin | At Day 1 and Day 15 | — |
| Part 2: Cmax for Itraconazole Following Comedication with VH4524184 | At Day 1 and Day 14 | — |
| Part 2: AUC0-t for Itraconazole Following Comedication with VH4524184 | At Day 1 and Day 14 | — |
| Part 2: Cmax for Rifabutin Following Comedication with VH4524184 | At Day 1 and Day 11 | — |
| Part 2: AUC0-t for Rifabutin Following Comedication with VH4524184 | At Day 1 and Day 19 | — |
| Part 2: Cmax for Phenytoin Following Comedication with VH4524184 | Day 1 and Day 22 | — |
| Part 2: AUC0-t for Phenytoin Following Comedication with VH4524184 | Day 1 and Day 22 | — |
Countries
United States
Outcome results
None listed