A Study to Evaluate VH4524184 Tablet Absorption, Effects of Food, and Interactions With Other Drugs in Healthy Adults

ViiV Healthcare

Status and phase: Enrolling; Phase 1

Conditions: HIV Infections

Treatments: Drug: Rifabutin; Drug: Metformin; Drug: Digoxin; Drug: VH4524184; Drug: Itraconazole; Drug: Phenytoin

Study type: Interventional

Funder types: Industry

Identifiers

NCT07066722

219890

Details and patient eligibility

About

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.

Enrollment: 124 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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124 participants in 12 patient groups

Part 1A_VH4524184 (Sequence 1)

Experimental group

Description:

Participants will receive VH4524184 tablet(s) of Dose level 1 followed by Dose level 2 in fasted condition.

Treatment:

Drug: VH4524184

Part 1A_VH4524184 (Sequence 2)

Experimental group

Description:

Participants will receive VH4524184 tablet(s) of Dose level 2 followed by Dose level 1 in fasted condition.

Treatment:

Drug: VH4524184

Part 1A_VH4524184 (Sequence 3)

Experimental group

Description:

Participants will receive VH4524184 tablet(s) of Dose level 3 followed by Dose level 2 in fasted condition.

Treatment:

Drug: VH4524184

Part 1A_VH4524184 (Sequence 4)

Experimental group

Description:

Participants will receive VH4524184 tablet(s) of Dose level 2 followed by Dose level 3 in fasted condition.

Treatment:

Drug: VH4524184

Part 1B_VH4524184 (Sequence 5)

Experimental group

Description:

Participants will receive VH4524184 tablet of Dose level 2 in fasted condition and then followed by intake of a high fat meal.

Treatment:

Drug: VH4524184

Part 1B_VH4524184 Sequence 6)

Experimental group

Description:

Participants will receive VH4524184 tablet of Dose level 2 following a high fat meal and then in fasted condition.

Treatment:

Drug: VH4524184

Part 1B_VH4524184 (Sequence 7)

Experimental group

Description:

Participants will receive VH4524184 tablet of Dose level 3 in fasted condition and then followed by intake of a high fat meal.

Treatment:

Drug: VH4524184

Part 1B_VH4524184 (Sequence 8)

Experimental group

Description:

Participants will receive VH4524184 tablet of Dose level 3 following a high fat meal and then in a fasted condition.

Treatment:

Drug: VH4524184

Part 2_Cohort 1

Experimental group

Description:

Participants will receive VH4524184 tablet and Itraconazole.

Treatment:

Drug: Itraconazole

Drug: VH4524184

Part 2_Cohort 2A

Experimental group

Description:

Participants will receive VH4524184 and Rifabutin.

Treatment:

Drug: VH4524184

Drug: Rifabutin

Part 2_Cohort 2B

Experimental group

Description:

Participants will receive VH4524184 tablet and Phenytoin.

Treatment:

Drug: Phenytoin

Drug: VH4524184

Part 2_ Cohort 3

Experimental group

Description:

Participants will receive Metformin, Digoxin and VH4524184 tablets.

Treatment:

Drug: VH4524184

Drug: Digoxin

Drug: Metformin