A Study to Investigate Safety, Tolerability, and Pharmacokinetics (PK) of VH4524184 and the Potential for Changes in Cytochrome P450 3A (CYP3A) Activity

ViiV Healthcare

Status and phase: Completed; Phase 1

Conditions: HIV Infections

Treatments: Drug: VH4524184; Drug: Placebo; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT05631704

218803

Details and patient eligibility

About

This study is designed to investigate the safety, tolerability and PK of VH4524184 (GSK4524184) and the potential of VH4524184 to inhibit or induce CYP3A activity in healthy participants.

Enrollment: 84 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Participant must be 18 to 50 years of age.
• Participants who are overtly healthy.
• Body weight >=50.0 kilograms (kg) (110 pounds [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 32.0 kilograms per meter square (kg/m^2) (inclusive).
• Male or female. Male Participants: No contraceptive restrictions for male participants. Female Participants: A female participant (female sex assigned at birth) is eligible to participate if she is not pregnant, or breastfeeding and is not physically able to have a baby.

Exclusion criteria

• History or presence of clinical condition that could significantly alter how medicines are absorbed, broken down or eliminated from the body; be risky to the participant, or make it difficult to interpret the data from the study.
• Pre-existing clinically relevant gastro-intestinal disorders.
• Abnormal blood pressure.
• Certain blood or other cancers within the past 5 years.
• Breast cancer within the past 10 years
• Current or chronic history of liver disease or liver or bile tract abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 milliseconds (msec).
• Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome.
• History of seizure
• Any known or suspected pre-existing psychiatric condition, including depression, anxiety and insomnia/sleep disturbances.
• Any positive (abnormal) response to the Columbia Suicide Severity Rating Scale (CSSRS).
• Past or intended use of over-the-counter or prescription medication within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing and for the duration of the study.
• Receipt of any live vaccine(s) or vaccines against Coronavirus disease 2019 (Covid-19) within 28 days prior to screening or plans to receive such vaccines during the study.
• Exposure to more than 4 new investigational products (including long-acting investigational products) within 12 months prior to the first dosing day.
• Current enrollment or past participation in another investigational study in which an investigational intervention (e.g., drug, human blood product, monoclonal antibody, vaccine, invasive device) was administered within the last 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent (OR screening) any other clinical study.
• Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) over a 56-day period.
• Current enrollment or past participation in this clinical study.
• Estimated Glomerular Filtration Rate (eGFR) <90 milliliters per minute (mL/min) (calculated using Chronic Kidney Disease Epidemiology Collaboration equation) or serum creatinine >1.1 times Upper limit of normal (ULN).
• Hemoglobin <12.5 grams per deciliter (g/dL) for men and <11 g/dL for women
• ALT or AST >1.5 times ULN
• Total bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]).
• Any significant arrhythmia or Electrocardiogram (ECG) finding
• Exclusion criteria for Screening ECG (a single repeat is allowed for eligibility determination): Heart rate:<45 or >100 beats per minute (bpm) (Males), <50 or >100 bpm (Females); PR interval: <120 or >220 msec; QRS duration: <70 or >120 msec and QTcF interval: >450 msec.
• Presence of hepatitis B surface antigen (HBsAg) at screening.
• Positive Hepatitis C antibody test result at screening
• Positive pre-study drug/alcohol screen.
• Positive human immunodeficiency virus (HIV) antibody test.
• Regular alcohol consumption within 6 months prior to the study
• Regular use of known drugs of abuse
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening and at admission.
• Sensitivity to the study drug, or components thereof, midazolam (For Part 2, midazolam probe cohort), excipients contained therein, benzodiazepines, or other drug or other allergy that, in the opinion of the investigator or Sponsor Medical Monitor, contraindicates participation in the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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84 participants in 19 patient groups, including a placebo group

Part 1: Cohort 1: Participants receiving VH4524184 DL1

Experimental group

Description:

Eligible participants will receive VH4524184 Dose Level 1 (DL1) during Cohort 1 of Part 1 of the study.

Treatment:

Drug: VH4524184

Part 1: Cohort 1: Participants receiving Placebo

Placebo Comparator group

Description:

Eligible participants will receive Placebo matching VH4524184 DL1 during Cohort 1 of Part 1 of the study.

Treatment:

Drug: Placebo

Part 1: Cohort 2: Participants receiving VH4524184 DL2

Experimental group

Description:

Eligible participants will receive VH4524184 DL2 during Cohort 2 of Part 1 of the study.

Treatment:

Drug: VH4524184

Part 1: Cohort 2: Participants receiving Placebo

Placebo Comparator group

Description:

Eligible participants will receive Placebo matching VH4524184 DL2 during Cohort 2 of Part 1 of the study.

Treatment:

Drug: Placebo

Part 1: Cohort 3: Participants receiving VH4524184 DL3

Experimental group

Description:

Eligible participants will receive VH4524184 DL3 during Cohort 3 of Part 1 of the study.

Treatment:

Drug: VH4524184

Part 1: Cohort 3: Participants receiving Placebo

Placebo Comparator group

Description:

Eligible participants will receive Placebo matching VH4524184 DL3 during Cohort 3 of Part 1 of the study.

Treatment:

Drug: Placebo

Part 1: Cohort 4: Participants receiving VH4524184 DL4

Experimental group

Description:

Eligible participants will receive VH4524184 DL4 during Cohort 4 of Part 1 of the study.

Treatment:

Drug: VH4524184

Part 1: Cohort 4: Participants receiving Placebo

Placebo Comparator group

Description:

Eligible participants will receive Placebo matching VH4524184 DL4 during Cohort 4 of Part 1 of the study.

Treatment:

Drug: Placebo

Part 1: Cohort 5: Participants receiving VH4524184 DL5

Experimental group

Description:

Eligible participants will receive VH4524184 DL5 during Cohort 5 (optional) of Part 1 of the study.

Treatment:

Drug: VH4524184

Part 1: Cohort 5: Participants receiving Placebo

Placebo Comparator group

Description:

Eligible participants will receive Placebo matching VH4524184 DL5 during Cohort 5 (optional) of Part 1 of the study.

Treatment:

Drug: Placebo

Part 1: Cohort 6: Participants receiving VH4524184 DL6

Experimental group

Description:

Eligible participants will receive VH4524184 DL6 during Cohort 6 (optional) of Part 1 of the study.

Treatment:

Drug: VH4524184

Part 1: Cohort 6: Participants receiving Placebo

Placebo Comparator group

Description:

Eligible participants will receive Placebo matching VH4524184 DL6 during Cohort 6 (optional) of Part 1 of the study.

Treatment:

Drug: Placebo

Part 2: Cohort 7: Participants receiving VH4524184 RL1

Experimental group

Description:

Eligible participants will receive VH4524184 Repeat dose Level 1 (RL1) during Cohort 7 (Part 2) of the study.

Treatment:

Drug: VH4524184

Part 2: Cohort 7: Participants receiving Placebo

Placebo Comparator group

Description:

Eligible participants will receive Placebo matching VH4524184 RL1 during Cohort 7 (Part 2) of the study.

Treatment:

Drug: Placebo

Part 2: Cohort 8: Participants receiving VH4524184 RL2

Experimental group

Description:

Eligible participants will receive VH4524184 RL2 during Cohort 8 (Part 2) of the study. If Cohort 8 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of VH4524184

Treatment:

Drug: Midazolam

Drug: VH4524184

Part 2: Cohort 8: Participants receiving Placebo

Placebo Comparator group

Description:

Eligible participants will receive Placebo matching VH4524184 RL2 during Cohort 8 (Part 2) of the study. If Cohort 8 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of Placebo matching VH4524184.

Treatment:

Drug: Midazolam

Drug: Placebo

Part 2: Cohort 9: Participants receiving VH4524184 RL3

Experimental group

Description:

Eligible participants will receive VH4524184 RL3 during Cohort 9 (Part 2) (optional) of the study. If Cohort 9 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of VH4524184.

Treatment:

Drug: Midazolam

Drug: VH4524184

Part 2: Cohort 9: Participants receiving Placebo

Placebo Comparator group

Description:

Eligible participants will receive Placebo matching VH4524184 RL3 during Cohort 9 (Part 2) (optional) of the study. If Cohort 9 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of Placebo matching VH4524184.

Treatment:

Drug: Midazolam

Drug: Placebo

Part 3: Cohort 10: VH4524184 Fasted/ VH4524184 Fed

Experimental group

Description:

Eligible participants will receive VH4524184 under fasted condition in Treatment Period 1 followed by VH4524184 under fed condition in Treatment Period 2 during Cohort 10 (Part 3) of the study. Treatment Periods will be separated by a washout period.

Treatment:

Drug: VH4524184