A Study to Investigate the Relative Bioavailability and Food Effect of an Oral Capsid Inhibitor Tablet Formulation Compared With Other Oral Tablet Formulations in Male and Female Healthy Participants

NCT06168318 | Completed Phase 1 FDA Drug

• 1 other identifier: 220095
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infections

Keywords

Human immunodeficiency virus; HIV-1; capsid inhibitor; VH4004280; food effect; fasted conditions; fed conditions; bioavailability

Outcome Measures

Primary Outcomes (4)

• 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

• 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

Secondary Outcomes (4)

• Number of participants with AEs (Adverse Events), by severity

  From Day 1 to Day 49

• Number of participants with maximum toxicity grade increase from baseline for liver laboratory parameters

  From Day 1 to Day 49

• 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

Study Arms (13)

Part 1 - Regimen A

EXPERIMENTAL

VH4004280 Formulation A tablet administered in fed conditions.

Drug: VH4004280 Formulation A

Part 1 - Regimen B

EXPERIMENTAL

VH4004280 Formulation B tablet administered in fed conditions.

Drug: VH4004280 Formulation B

Part 1 - Regimen C

EXPERIMENTAL

VH4004280 Formulation C tablet administered in fed conditions.

Drug: VH4004280 Formulation C

Part 1 - Optional Regimen D

EXPERIMENTAL

VH4004280 Formulation D tablet administered in fed conditions.

Drug: VH4004280 Formulation D

Part 1 - Optional Regimen E

EXPERIMENTAL

VH4004280 Formulation E tablet administered in fed conditions.

Drug: VH4004280 Formulation E

Part 2 - Regimen A

EXPERIMENTAL

VH4004280 Formulation A tablet administered in fasted conditions.

Drug: VH4004280 Formulation A

Part 2- Optional Regimen 1

EXPERIMENTAL

VH4004280 Formulation B, C, D, or E tablet administered in fasted conditions.

Drug: VH4004280 Formulation B; Drug: VH4004280 Formulation C; Drug: VH4004280 Formulation D; Drug: VH4004280 Formulation E

Part 2- Optional Regimen 2

EXPERIMENTAL

VH4004280 Formulation B, C, D, or E tablet administered in fasted conditions.

Drug: VH4004280 Formulation B; Drug: VH4004280 Formulation C; Drug: VH4004280 Formulation D; Drug: VH4004280 Formulation E

Part 2- Optional Regimen 3

EXPERIMENTAL

VH4004280 Formulation B, C, D, or E tablet administered in fasted conditions.

Drug: VH4004280 Formulation B; Drug: VH4004280 Formulation C; Drug: VH4004280 Formulation D; Drug: VH4004280 Formulation E

Part 3 - Optional Regimen 1

EXPERIMENTAL

VH4004280 Formulation A, B, C or D tablet administered in lower fat conditions.

Drug: VH4004280 Formulation A; Drug: VH4004280 Formulation B; Drug: VH4004280 Formulation C; Drug: VH4004280 Formulation D

Part 3- Optional Regimen 2

EXPERIMENTAL

VH4004280 Formulation A, B, C or D tablet administered in lower fat conditions.

Drug: VH4004280 Formulation A; Drug: VH4004280 Formulation B; Drug: VH4004280 Formulation C; Drug: VH4004280 Formulation D

Part 3 - Optional Regimen 3

EXPERIMENTAL

VH4004280 Formulation A, B, C or D tablet administered in lower fat conditions.

Drug: VH4004280 Formulation A; Drug: VH4004280 Formulation B; Drug: VH4004280 Formulation C; Drug: VH4004280 Formulation D

Part 3 - Optional Regimen 4

EXPERIMENTAL

VH4004280 Formulation A, B, C or D tablet administered in lower fat conditions.

Drug: VH4004280 Formulation A; Drug: VH4004280 Formulation B; Drug: VH4004280 Formulation C; Drug: VH4004280 Formulation D

Interventions

VH4004280 Formulation A DRUG

Oral administration of VH4004280 Formulation A in fasted or fed conditions.

Part 1 - Regimen A; Part 2 - Regimen A; Part 3 - Optional Regimen 1; Part 3 - Optional Regimen 3; Part 3 - Optional Regimen 4; Part 3- Optional Regimen 2

VH4004280 Formulation B DRUG

Oral administration of VH4004280 Formulation B in fasted or fed conditions.

Part 1 - Regimen B; Part 2- Optional Regimen 1; Part 2- Optional Regimen 2; Part 2- Optional Regimen 3; Part 3 - Optional Regimen 1; Part 3 - Optional Regimen 3; Part 3 - Optional Regimen 4; Part 3- Optional Regimen 2

VH4004280 Formulation C DRUG

Oral administration of VH4004280 Formulation C in fasted or fed conditions.

Part 1 - Regimen C; Part 2- Optional Regimen 1; Part 2- Optional Regimen 2; Part 2- Optional Regimen 3; Part 3 - Optional Regimen 1; Part 3 - Optional Regimen 3; Part 3 - Optional Regimen 4; Part 3- Optional Regimen 2

VH4004280 Formulation D DRUG

Oral administration of VH4004280 Formulation D in fasted or fed conditions.

Part 1 - Optional Regimen D; Part 2- Optional Regimen 1; Part 2- Optional Regimen 2; Part 2- Optional Regimen 3; Part 3 - Optional Regimen 1; Part 3 - Optional Regimen 3; Part 3 - Optional Regimen 4; Part 3- Optional Regimen 2

VH4004280 Formulation E DRUG

Oral administration of VH4004280 Formulation E in fasted or fed conditions.

Part 1 - Optional Regimen E; Part 2- Optional Regimen 1; Part 2- Optional Regimen 2; Part 2- Optional Regimen 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must be 18 to 55years of age.
• Participants who are overtly healthy.
• Negative (Severe Acute Respiratory Syndrome Coronavirus 2) SARs-CoV-2 test prior to dosing.
• Has body mass index (BMI) within the range 19-32 (kg/m2).
• 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.
• Capable of giving signed informed consent.

You may not qualify if:

• History or presence of disorders capable of significantly altering the absorption, metabolism, or elimination of drugs.
• Abnormal blood pressure.
• Any malignancy within the past 5 years except certain localized malignancies, or breast cancer within the past 10 years.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities.
• Exposure \> 4 new investigational products within 12 months, previous participation in this study, or current enrolment or participation in another investigational study.
• ALT \>1.5x upper limit of normal (ULN), total bilirubin \>1.5x ULN, and/or estimated serum creatinine clearance \<60 mL/min.
• History of or current infection with hepatitis B or hepatitis C.
• Positive SARS-CoV-2 test, having signs and symptoms suggestive of COVID-19, or contact with known COVID-19 positive person.
• Positive HIV antibody test.
• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (1)

GSK Investigational Site

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2023
• First Posted: December 13, 2023
• Study Start: December 18, 2023
• Primary Completion: June 3, 2024
• Study Completion: June 3, 2024
• Last Updated: August 2, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

GB (1)