VH3739937 Phase 1 Multiple Ascending Dose (MAD) Study in Healthy Volunteers Including Relative Bioavailability (RBA), Optional Food Effect (FE), and Drug-drug Interaction (DDI)
NCT Number: NCT06533280
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: HIV Infections
Interventions: DRUG: Part A, C and D: VH3739937 500 mg|DRUG: Part A: VH3739937 100 mg|DRUG: Part A and C: Placebo|DRUG: Part B: Treatment A|DRUG: Part B: Treatment B|DRUG: Part B: Treatment C|DRUG: Part B: Treatment D|DRUG: Part B: Treatment E|DRUG: Part D: Probe cocktail
Sponsor: ViiV Healthcare
Sex: ALL
Age: ADULT
Enrollment: 91
Study Design: Allocation: RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-08-02
Completion Date: 2025-03-14
Locations: GSK Investigational Site, Baltimore, Maryland, 21225, United States

Summary:
This study will assess safety, tolerability and pharmacokinetic (PK) of VH3739937 in healthy participants.

Primary Outcome Measures: Part A: Number of participants with any adverse events (AEs), Up to Day 25 for Cohorts A1 and A2 and Day 30 for Cohort A3|Part B: Number of participants with any adverse events (AEs), Up to Day 15|Part C: Number of participants with any adverse events (AEs), Up to Day 42|Part D: Number of participants with any adverse events (AEs), Up to Day 28|Part A: Number of participants with adverse events (AEs) by grade of severity, The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening., Up to Day 25 for Cohorts A1 and A2, and Day 30 for Cohort A3|Part B: Number of participants with adverse events (AEs) by grade of severity, The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening., Up to Day 15 (Periods 2 and 4 only)|Part C: Number of participants with adverse events (AEs) by grade of severity, The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening., Up to Day 42|Part D: Number of participants with adverse events (AEs) by grade of severity, The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening., Up to Day 28|Part A: Number of participants with any serious adverse events (SAEs), Up to Day 25 for Cohort A1 and A2 and Day 30 for Cohort A3|Part B: Number of participants with any serious adverse events (SAEs), Up to Day 15 (Periods 2 and 4 only)|Part C: Number of participants with any serious adverse events (SAEs), Up to Day 42|Part D: Number of participants with any serious adverse events (SAEs), Up to Day 28|Part A: Number of participants with serious adverse events (SAEs) by grade of severity, The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening., Up to Day 25 for Cohort A1 and A2, and Day 30 for Cohort A3|Part B: Number of participants with serious adverse events (SAEs) by grade of severity, The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening., Up to Day 15 (Periods 2 and 4 only)|Part C: Number of participants with serious adverse events (SAEs) by grade of severity, The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening., Up to Day 42|Part D: Number of participants with serious adverse events (SAEs) by grade of severity, The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening., Up to Day 28|Part B: Area under the plasma concentration over a dosing interval from time of dosing to the time of the subsequent dose (AUC[0-t]), At Days 1 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)|Part B: AUC time curve from time zero to infinity (AUC[0-infinity]), At Days 1 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)|Part B: Time to maximum observed plasma concentration (Tmax), At Days 1 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)|Part B: Maximum observed plasma concentration (Cmax) after VH3739937 administration, At Days 1 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)
Secondary Outcome Measures: Part B: AUC to the end of the dosing period (AUC[0-tau]) after VH3739937 administration, At Days 1, 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)|Part B: AUC[0-infinity] after VH3739937 administration, At Days 1, 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)|Part B: Tmax after VH3739937 administration, At Days 1, 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)|Part B: Apparent terminal half-life (T1/2) after VH3739937 administration, At Days 1, 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)|Part B: Apparent Oral Clearance (CL/F) after VH3739937 administration, At Days 1, 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)|Part D: AUC[0-tau] after VH3739937 administration, At Day 10 and Day 11|Part D: AUC[0-infinity] after VH3739937 administration, At Day 10 and Day 11|Part D: Cmax after VH3739937 administration, At Day 10 and Day 11|Part D: Tmax after VH3739937 administration, At Day 10 and Day 11|Part D: T1/2 after VH3739937 administration, At Day 10 and Day 11|Part D: CL/F after VH3739937 administration, At Day 10 and Day 11|Part A: AUC[0-tau] after VH3739937 administration, At Days 1 to 6, 8, 11, 15, 20, 25 (Cohort A1), at Days 1, 3 to 9, 11, 15, 20, 25 (Cohort A2), at Days 1, 4 to 8 , 10, 14, 18, 25, Day 30 (Cohort A3)|Part A: Cmax after VH3739937 administration, At Days 1 to 6, 8, 11, 15, 20, 25 (Cohort A1), at Days 1, 3 to 9, 11, 15, 20, 25 (Cohort A2), at Days 1, 4 to 8 , 10, 14, 18, 25, Day 30 (Cohort A3)|Part A: Tmax after VH3739937 administration, At Days 1 to 6, 8, 11, 15, 20, 25 (Cohort A1), at Days 1, 3 to 9, 11, 15, 20, 25 (Cohort A2), at Days 1, 4 to 8 , 10, 14, 18, 25, Day 30 (Cohort A3)|Part A: T1/2 after VH3739937 administration, At Days 1 to 6, 8, 11, 15, 20, 25 (Cohort A1), at Days 1, 3 to 9, 11, 15, 20, 25 (Cohort A2), at Days 1, 4 to 8 , 10, 14, 18, 25, Day 30 (Cohort A3)|Part C: AUC[0-tau] after VH3739937 administration, At Days 1, 2, 5, 7, 8, 9, 13, 15, 16, 17, 26, 34 and 42|Part C: Concentration in a dosing interval (Ctau) after VH3739937 administration, At Days 1, 2, 5, 7, 8, 9, 13, 15, 16, 17, 26, 34 and 42|Part C: Cmax after VH3739937 administration, At Days 1, 2, 5, 7, 8, 9, 13, 15, 16, 17, 26, 34 and 42|Part C: Tmax after VH3739937 administration, At Days 1, 2, 5, 7, 8, 9, 13, 15, 16, 17, 26, 34 and 42|Part C: T1/2 after VH3739937 administration, At Days 1, 2, 5, 7, 8, 9, 13, 15, 16, 17, 26, 34 and 42|Part C: CL/F after VH3739937 administration, At Days 1, 2, 5, 7, 8, 9, 13, 15, 16, 17, 26, 34 and 42|Part D: AUC[0-infinity] after probe cocktail administration, At Day 10 and Day 11|Part D: Cmax after probe cocktail administration, At Day 10 and Day 11|Part D: Tmax after probe cocktail administration, At Day 10 and Day 11|Part D: T1/2 after probe cocktail administration, At Day 10 and Day 11|Part D: CL/F after probe cocktail administration, At Day 10 and Day 11|Change from baseline for heart rate over all study groups, Up to Day 25 for Part A (Cohort A1 and A2) and Day 30 (Cohort A3), Day 15 for Part B, Day 17 and Day 42 for Part C, Day 14 and Day 28 for Part D|Change from baseline in PR Interval, QRS Interval, and QT Interval corrected for heart rate using Fridericias formula (QTcF) over all study groups, At Days (D) 1 to 5, 8, 15, 25 for Cohort A1 (Part A), D 1 to 6, 9, 15, 25 for Cohort A2 (Part A), D 1 to 7, 10, 18, 30 for Cohort A3 (Part A), at D 1, 3, 6, 12,15 for Part B, at D 1, 2, 8, 9, 13 to 17, 42 for Part C, at D 1, 3, 10, 14, 28 for Part D|Placebo-corrected change from baseline heart rate over alll study groups, At Days (D) 1 to 5, 8, 15, 25 for Cohort A1 (Part A), D 1 to 6, 9, 15, 25 for Cohort A2 (Part A), D 1 to 7, 10, 18, 30 for Cohort A3 (Part A), at D 1, 3, 6, 12,15 for Part B, at D 1, 2, 8, 9, 13 to 17, 42 for Part C, at D 1, 3, 10, 14, 28 for Part D|Placebo-corrected change from baseline in PR Interval, QRS Interval, and QT Interval corrected for heart rate using Fridericias formula (QTcF) over all study groups, At Days (D) 1 to 5, 8, 15, 25 for Cohort A1 (Part A), D 1 to 6, 9, 15, 25 for Cohort A2 (Part A), D 1 to 7, 10, 18, 30 for Cohort A3 (Part A), at D 1, 3, 6, 12,15 for Part B, at D 1, 2, 8, 9, 13 to 17, 42 for Part C, at D 1, 3, 10, 14, 28 for Part D|Categorical outliers for heart rate, PR Interval, QRS Interval and QT Interval over all study groups, At Days (D) 1 to 5, 8, 15, 25 for Cohort A1 (Part A), D 1 to 6, 9, 15, 25 for Cohort A2 (Part A), D 1 to 7, 10, 18, 30 for Cohort A3 (Part A), at D 1, 3, 6, 12,15 for Part B, at D 1, 2, 8, 9, 13 to 17, 42 for Part C, at D 1, 3, 10, 14, 28 for Part D|Frequency of treatment-emergent electrocardiogram (ECG) morphology changes over all study groups, At Days (D) 1 to 5, 8, 15, 25 for Cohort A1 (Part A), D 1 to 6, 9, 15, 25 for Cohort A2 (Part A), D 1 to 7, 10, 18, 30 for Cohort A3 (Part A), at D 1, 3, 6, 12,15 for Part B, at D 1, 2, 8, 9, 13 to 17, 42 for Part C, at D 1, 3, 10, 14, 28 for Part D