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

Primary Purpose

HIV Infections

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VH4524184
Midazolam
Placebo
Sponsored by
ViiV Healthcare
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring First-time-in-human, GSK4524184, Healthy volunteers, Multiple Ascending Dose, Single Ascending Dose, VH4524184

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts 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.

Sites / Locations

  • GSK Investigational SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm 18

Arm 19

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

Part 1: Cohort 1: Participants receiving VH4524184 DL1

Part 1: Cohort 1: Participants receiving Placebo

Part 1: Cohort 2: Participants receiving VH4524184 DL2

Part 1: Cohort 2: Participants receiving Placebo

Part 1: Cohort 3: Participants receiving VH4524184 DL3

Part 1: Cohort 3: Participants receiving Placebo

Part 1: Cohort 4: Participants receiving VH4524184 DL4

Part 1: Cohort 4: Participants receiving Placebo

Part 1: Cohort 5: Participants receiving VH4524184 DL5

Part 1: Cohort 5: Participants receiving Placebo

Part 1: Cohort 6: Participants receiving VH4524184 DL6

Part 1: Cohort 6: Participants receiving Placebo

Part 2: Cohort 7: Participants receiving VH4524184 RL1

Part 2: Cohort 7: Participants receiving Placebo

Part 2: Cohort 8: Participants receiving VH4524184 RL2

Part 2: Cohort 8: Participants receiving Placebo

Part 2: Cohort 9: Participants receiving VH4524184 RL3

Part 2: Cohort 9: Participants receiving Placebo

Part 3: Cohort 10: VH4524184 Fasted/ VH4524184 Fed

Arm Description

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Part 1: Number of participants with serious adverse events (SAE) and non-serious adverse events (non-SAE)
Part 2: Number of participants with SAE and non-SAE
Part 3: Number of participants with SAE and non-SAE
Part 1: Number of participants with adverse events based on severity
Part 2: Number of participants with adverse events by severity
Part 3: Number of participants with adverse events based on severity
Part 1: Percentage of participants who discontinue treatment due to adverse events (AE)
Part 2: Percentage of participants who discontinue treatment due to AE
Part 3: Percentage of participants who discontinue treatment due to AE
Part 1: Change from Baseline in Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) (International units per liter)
Part 2: Change from Baseline in AST, ALT and ALP (International units per liter)
Part 3: Change from Baseline in AST, ALT and ALP (International units per liter)
Part 1: Change from Baseline in Total bilirubin and Direct bilirubin (Micromoles per liter)
Part 2: Change from Baseline in Total bilirubin and Direct bilirubin (Micromoles per liter)
Part 3: Change from Baseline in Total bilirubin and Direct bilirubin (Micromoles per liter)
Part 1: Change from Baseline in Prothrombin time and Partial Thromboplastin Time (Seconds)
Part 2: Change from Baseline in Prothrombin time and Partial Thromboplastin Time (Seconds)
Part 3: Change from Baseline in Prothrombin time and Partial Thromboplastin Time (Seconds)
Part 1: Change from Baseline in International normalized ratio (INR) (Ratio)
Part 2: Change from Baseline in INR (Ratio)
Part 3: Change from Baseline in INR (Ratio)
Part 1: Number of participants with maximum toxicity grade increase from Baseline in liver panel laboratory parameters; AST, ALT, ALP, Total bilirubin, Direct bilirubin, Prothrombin time, Partial Thromboplastin Time and INR
Part 2: Number of participants with maximum toxicity grade increase from Baseline in liver panel laboratory parameters; AST, ALT, ALP, Total bilirubin, Direct bilirubin, Prothrombin time, Partial Thromboplastin Time and INR
Part 3: Number of participant with maximum toxicity grade increase from Baseline in liver panel laboratory parameters; AST, ALT, ALP, Total bilirubin, Direct bilirubin, Prothrombin time, Partial Thromboplastin Time and INR
Part 1: Area under the plasma-concentration time curve from zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) following dosing of VH4524184
Part 2: Area under the plasma concentration-time curve from zero (pre-dose) to the end of the dosing interval at steady state (AUC[0-tau]) following dosing of VH4524184
Part 1: Maximum observed plasma drug concentration (Cmax) following dosing of VH4524184
Part 2: Cmax following dosing of VH4524184
Part 1: Time to maximum observed plasma drug concentration (tmax) following dosing of VH4524184
Part 2: Tmax following dosing of VH4524184
Part 1: Apparent terminal half-life (t1/2) following dosing of VH4524184
Part 2: T1/2 following dosing of VH4524184

Secondary Outcome Measures

Part 1: Number of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities
Part 2: Number of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities
Part 3: Number of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities

Full Information

First Posted
November 18, 2022
Last Updated
January 11, 2023
Sponsor
ViiV Healthcare
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1. Study Identification

Unique Protocol Identification Number
NCT05631704
Brief Title
A Study to Investigate Safety, Tolerability, and Pharmacokinetics (PK) of VH4524184 and the Potential for Changes in Cytochrome P450 3A (CYP3A) Activity
Official Title
A Phase 1 Double-Blind (Sponsor-unblinded), Placebo-Controlled Randomized, Single and Multiple Ascending Dose First-Time-in-Human Study to Investigate the Safety, Tolerability, and Pharmacokinetics of VH4524184 and the Potential for Changes in Cytochrome P450 3A (CYP3A) Activity
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 2, 2022 (Actual)
Primary Completion Date
August 31, 2023 (Anticipated)
Study Completion Date
August 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ViiV Healthcare

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
First-time-in-human, GSK4524184, Healthy volunteers, Multiple Ascending Dose, Single Ascending Dose, VH4524184

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Participants will receive escalating doses of VH4524184 or placebo in Part 1 and Part 2 of the study. In Part 3, participants will receive VH4524184 under fasted and fed conditions.
Masking
ParticipantInvestigator
Masking Description
This will be a double blind study.
Allocation
Randomized
Enrollment
105 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Cohort 1: Participants receiving VH4524184 DL1
Arm Type
Experimental
Arm Description
Eligible participants will receive VH4524184 Dose Level 1 (DL1) during Cohort 1 of Part 1 of the study.
Arm Title
Part 1: Cohort 1: Participants receiving Placebo
Arm Type
Placebo Comparator
Arm Description
Eligible participants will receive Placebo matching VH4524184 DL1 during Cohort 1 of Part 1 of the study.
Arm Title
Part 1: Cohort 2: Participants receiving VH4524184 DL2
Arm Type
Experimental
Arm Description
Eligible participants will receive VH4524184 DL2 during Cohort 2 of Part 1 of the study.
Arm Title
Part 1: Cohort 2: Participants receiving Placebo
Arm Type
Placebo Comparator
Arm Description
Eligible participants will receive Placebo matching VH4524184 DL2 during Cohort 2 of Part 1 of the study.
Arm Title
Part 1: Cohort 3: Participants receiving VH4524184 DL3
Arm Type
Experimental
Arm Description
Eligible participants will receive VH4524184 DL3 during Cohort 3 of Part 1 of the study.
Arm Title
Part 1: Cohort 3: Participants receiving Placebo
Arm Type
Placebo Comparator
Arm Description
Eligible participants will receive Placebo matching VH4524184 DL3 during Cohort 3 of Part 1 of the study.
Arm Title
Part 1: Cohort 4: Participants receiving VH4524184 DL4
Arm Type
Experimental
Arm Description
Eligible participants will receive VH4524184 DL4 during Cohort 4 of Part 1 of the study.
Arm Title
Part 1: Cohort 4: Participants receiving Placebo
Arm Type
Placebo Comparator
Arm Description
Eligible participants will receive Placebo matching VH4524184 DL4 during Cohort 4 of Part 1 of the study.
Arm Title
Part 1: Cohort 5: Participants receiving VH4524184 DL5
Arm Type
Experimental
Arm Description
Eligible participants will receive VH4524184 DL5 during Cohort 5 (optional) of Part 1 of the study.
Arm Title
Part 1: Cohort 5: Participants receiving Placebo
Arm Type
Placebo Comparator
Arm Description
Eligible participants will receive Placebo matching VH4524184 DL5 during Cohort 5 (optional) of Part 1 of the study.
Arm Title
Part 1: Cohort 6: Participants receiving VH4524184 DL6
Arm Type
Experimental
Arm Description
Eligible participants will receive VH4524184 DL6 during Cohort 6 (optional) of Part 1 of the study.
Arm Title
Part 1: Cohort 6: Participants receiving Placebo
Arm Type
Placebo Comparator
Arm Description
Eligible participants will receive Placebo matching VH4524184 DL6 during Cohort 6 (optional) of Part 1 of the study.
Arm Title
Part 2: Cohort 7: Participants receiving VH4524184 RL1
Arm Type
Experimental
Arm Description
Eligible participants will receive VH4524184 Repeat dose Level 1 (RL1) during Cohort 7 (Part 2) of the study.
Arm Title
Part 2: Cohort 7: Participants receiving Placebo
Arm Type
Placebo Comparator
Arm Description
Eligible participants will receive Placebo matching VH4524184 RL1 during Cohort 7 (Part 2) of the study.
Arm Title
Part 2: Cohort 8: Participants receiving VH4524184 RL2
Arm Type
Experimental
Arm 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
Arm Title
Part 2: Cohort 8: Participants receiving Placebo
Arm Type
Placebo Comparator
Arm 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.
Arm Title
Part 2: Cohort 9: Participants receiving VH4524184 RL3
Arm Type
Experimental
Arm 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.
Arm Title
Part 2: Cohort 9: Participants receiving Placebo
Arm Type
Placebo Comparator
Arm 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.
Arm Title
Part 3: Cohort 10: VH4524184 Fasted/ VH4524184 Fed
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
VH4524184
Intervention Description
VH4524184 will be administered.
Intervention Type
Drug
Intervention Name(s)
Midazolam
Intervention Description
Midazolam will be administered in the highest dose cohort in Part 2 (Cohorts 8 or 9).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be administered.
Primary Outcome Measure Information:
Title
Part 1: Number of participants with serious adverse events (SAE) and non-serious adverse events (non-SAE)
Time Frame
Up to 4 weeks
Title
Part 2: Number of participants with SAE and non-SAE
Time Frame
Up to 6.5 weeks
Title
Part 3: Number of participants with SAE and non-SAE
Time Frame
Up to 6.5 weeks
Title
Part 1: Number of participants with adverse events based on severity
Time Frame
Up to 4 weeks
Title
Part 2: Number of participants with adverse events by severity
Time Frame
Up to 6.5 weeks
Title
Part 3: Number of participants with adverse events based on severity
Time Frame
Up to 6.5 weeks
Title
Part 1: Percentage of participants who discontinue treatment due to adverse events (AE)
Time Frame
Up to 4 weeks
Title
Part 2: Percentage of participants who discontinue treatment due to AE
Time Frame
Up to 6.5 weeks
Title
Part 3: Percentage of participants who discontinue treatment due to AE
Time Frame
Up to 6.5 weeks
Title
Part 1: Change from Baseline in Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) (International units per liter)
Time Frame
Baseline (Day 1) and up to 4 weeks
Title
Part 2: Change from Baseline in AST, ALT and ALP (International units per liter)
Time Frame
Baseline (Day 1) and up to 6.5 weeks
Title
Part 3: Change from Baseline in AST, ALT and ALP (International units per liter)
Time Frame
Baseline (Day 1) and up to 6.5 weeks
Title
Part 1: Change from Baseline in Total bilirubin and Direct bilirubin (Micromoles per liter)
Time Frame
Baseline (Day 1) and up to 4 weeks
Title
Part 2: Change from Baseline in Total bilirubin and Direct bilirubin (Micromoles per liter)
Time Frame
Baseline (Day 1) and up to 6.5 weeks
Title
Part 3: Change from Baseline in Total bilirubin and Direct bilirubin (Micromoles per liter)
Time Frame
Baseline (Day 1) and up to 6.5 weeks
Title
Part 1: Change from Baseline in Prothrombin time and Partial Thromboplastin Time (Seconds)
Time Frame
Baseline (Day 1) and up to 4 weeks
Title
Part 2: Change from Baseline in Prothrombin time and Partial Thromboplastin Time (Seconds)
Time Frame
Baseline (Day 1) and up to 6.5 weeks
Title
Part 3: Change from Baseline in Prothrombin time and Partial Thromboplastin Time (Seconds)
Time Frame
Baseline (Day 1) and up to 6.5 weeks
Title
Part 1: Change from Baseline in International normalized ratio (INR) (Ratio)
Time Frame
Baseline (Day 1) and up to 4 weeks
Title
Part 2: Change from Baseline in INR (Ratio)
Time Frame
Baseline (Day 1) and up to 6.5 weeks
Title
Part 3: Change from Baseline in INR (Ratio)
Time Frame
Baseline (Day 1) and up to 6.5 weeks
Title
Part 1: Number of participants with maximum toxicity grade increase from Baseline in liver panel laboratory parameters; AST, ALT, ALP, Total bilirubin, Direct bilirubin, Prothrombin time, Partial Thromboplastin Time and INR
Time Frame
Baseline (Day 1) and up to 4 weeks
Title
Part 2: Number of participants with maximum toxicity grade increase from Baseline in liver panel laboratory parameters; AST, ALT, ALP, Total bilirubin, Direct bilirubin, Prothrombin time, Partial Thromboplastin Time and INR
Time Frame
Baseline (Day 1) and up to 6.5 weeks
Title
Part 3: Number of participant with maximum toxicity grade increase from Baseline in liver panel laboratory parameters; AST, ALT, ALP, Total bilirubin, Direct bilirubin, Prothrombin time, Partial Thromboplastin Time and INR
Time Frame
Baseline (Day 1) and up to 6.5 weeks
Title
Part 1: Area under the plasma-concentration time curve from zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) following dosing of VH4524184
Time Frame
Up to 4 weeks
Title
Part 2: Area under the plasma concentration-time curve from zero (pre-dose) to the end of the dosing interval at steady state (AUC[0-tau]) following dosing of VH4524184
Time Frame
Up to 6.5 weeks
Title
Part 1: Maximum observed plasma drug concentration (Cmax) following dosing of VH4524184
Time Frame
Up to 4 weeks
Title
Part 2: Cmax following dosing of VH4524184
Time Frame
Up to 6.5 weeks
Title
Part 1: Time to maximum observed plasma drug concentration (tmax) following dosing of VH4524184
Time Frame
Up to 4 weeks
Title
Part 2: Tmax following dosing of VH4524184
Time Frame
Up to 6.5 weeks
Title
Part 1: Apparent terminal half-life (t1/2) following dosing of VH4524184
Time Frame
Up to 4 weeks
Title
Part 2: T1/2 following dosing of VH4524184
Time Frame
Up to 6.5 weeks
Secondary Outcome Measure Information:
Title
Part 1: Number of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities
Time Frame
Up to 4 weeks
Title
Part 2: Number of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities
Time Frame
Up to 6.5 weeks
Title
Part 3: Number of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities
Time Frame
Up to 6.5 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name or Official Title & Degree
EU GSK Clinical Trials Call Center
Phone
+44 (0) 20 89904466
Email
GSKClinicalSupportHD@gsk.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
ViiV Healthcare
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21225
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
Ronald Goldwater

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Learn more about this trial

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

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