HIV Infections
Conditions
Keywords
Human immunodeficiency virus, HIV-1, capsid inhibitor, VH4004280, food effect, fasted conditions, fed conditions, bioavailability
Brief summary
This is a 3 part study of an investigational capsid inhibitor, VH4004280, in healthy adult participants. The purpose is to evaluate the effect of tablet formulation as well as food on bioavailability. Part 1 of the study will compare the relative bioavailability of VH4004280 Formulation A tablets to up to 4 alternative tablet formulations under fed (high fat) conditions. Part 2 of the study will assess the effect of fasted conditions on the bioavailability of VH4004280 Formulation A and alternative, optional formulations, relative to their respective bioavailability under fed conditions in Part 1. The optional Part 3 of the study will assess relative bioavailability of VH4004280 Formulation A to up to 3 alternative formulations, selected from Regimens B, C or D, under fed (lower fat) conditions.
Interventions
DRUGVH4004280 Formulation C
Oral administration of VH4004280 Formulation C in fasted or fed conditions.
DRUGVH4004280 Formulation D
Oral administration of VH4004280 Formulation D in fasted or fed conditions.
DRUGVH4004280 Formulation A
Oral administration of VH4004280 Formulation A in fasted or fed conditions.
DRUGVH4004280 Formulation B
Oral administration of VH4004280 Formulation B in fasted or fed conditions.
DRUGVH4004280 Formulation E
Oral administration of VH4004280 Formulation E in fasted or fed conditions.
Sponsors
ViiV Healthcare
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participants must be 18 to 55years of age. 2. Participants who are overtly healthy. 3. Negative (Severe Acute Respiratory Syndrome Coronavirus 2) SARs-CoV-2 test prior to dosing. 4. Has body mass index (BMI) within the range 19-32 (kg/m2). 5. Participants male at birth must use male condoms, and participants female at birth who are of childbearing potential must be using acceptable forms of birth control. 6. Capable of giving signed informed consent.
Exclusion criteria
1. History or presence of disorders capable of significantly altering the absorption, metabolism, or elimination of drugs. 2. Abnormal blood pressure. 3. Any malignancy within the past 5 years except certain localized malignancies, or breast cancer within the past 10 years. 4. Has exclusionary psychiatric, hepatic, cardiovascular, gastrointestinal, respiratory, endocrine, neurological, hematological, or renal condition. 5. Current or chronic history of liver disease or known hepatic or biliary abnormalities. 6. Participants with exclusionary electrocardiogram findings. 7. Past or intended use of exclusionary medications or vaccines. 8. Exposure \> 4 new investigational products within 12 months, previous participation in this study, or current enrolment or participation in another investigational study. 9. ALT \>1.5x upper limit of normal (ULN), total bilirubin \>1.5x ULN, and/or estimated serum creatinine clearance \<60 mL/min. 10. History of or current infection with hepatitis B or hepatitis C. 11. Positive SARS-CoV-2 test, having signs and symptoms suggestive of COVID-19, or contact with known COVID-19 positive person. 12. Positive HIV antibody test. 13. Participants with positive results for illicit drug use, regular use of drugs of abuse, tobacco or nicotine-containing product use, and/or excessive alcohol use.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to maximum observed plasma concentration (Tmax) of VH4004280 in fed conditions (after a high-fat or lower-fat meal) | From Day 1 to Day 49 |
| Area under the plasma concentration - time curve from time zero (pre-dose) to infinity time (AUC[0-inf]) of VH4004280 in fed conditions (after a high-fat or lower-fat meal) | From Day 1 to Day 49 |
| Area under the plasma drug concentration - time curve from zero (pre-dose) to the end of the dosing interval at steady state (AUC[0-tlast) of VH4004280 in fed conditions (after a high-fat or lower-fat meal) | From Day 1 to Day 49 |
| Maximum observed plasma drug concentration (Cmax) of VH4004280 in fed conditions(after a high-fat or lower-fat meal) | From Day 1 to Day 49 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with AEs (Adverse Events), by severity | From Day 1 to Day 49 | An AE is any untoward medical occurrence in a participant or clinical investigation participant and can be any sign, symptom, or disease temporally associated with the use of a medicinal product. The severity scale is assessed as following: Grade 1 = mild symptoms causing no or minimal interference with usual social and functional activities with intervention not indicated. Grade 2 = moderate symptoms causing greater than minimal interference with usual social and functional activities with intervention indicated. Grade 3 = severe symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated. Grade 4 = potentially life-threatening symptoms causing inability to perform self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death. |
| Number of participants with maximum toxicity grade increase from baseline for liver laboratory parameters | From Day 1 to Day 49 | The assessed laboratory assessments include Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), alkaline phosphatase (ALP), direct bilirubin and total bilirubin, in both fed and fasted conditions. |
| Change from baseline in liver panel parameters: Total bilirubin and direct bilirubin (micromoles per liter) | From Day 1 to Day 49 | — |
| Change from baseline in liver panel parameters: ALT, ALP and AST (International units per liter) | From Day 1 to Day 49 | — |
Countries
United Kingdom
Outcome results
None listed