First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4004280 in Healthy Participants
- Registration Number
- NCT05163522
- Lead Sponsor
- ViiV Healthcare
- Brief Summary
This FTIH study aims to evaluate the safety, tolerability and PK of the novel investigational Human immunodeficiency virus (HIV)-1 capsid inhibitor VH4004280 in healthy adults. The study will be conducted in 3 parts: Part 1 will investigate single ascending doses (SAD), Part 2 will investigate multiple ascending doses and drug-drug interaction (MAD/MAD DDI) Part 3 will investigate single dose relative bioavailability (RBA) of a new formulation of VH4004280.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 73
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 (SAD): VH4004280 10 mg PiB VH4004280 Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. Part 1 (SAD): VH4004280 900 mg PiB VH4004280 Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. Part 2 Multiple Ascending Dose (MAD): Placebo PiB Placebo Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63. Part 2 (MAD): VH4004280 100 mg PiB VH4004280 Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63. Part 2 (MAD): VH4004280 350 mg PiB VH4004280 Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63. Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) Placebo Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49. Part 1 (SAD): VH4004280 150 mg PiB VH4004280 Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB Midazolam Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63. Part 1 (SAD): VH4004280 50 mg PiB VH4004280 Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. Part 1 (SAD): VH4004280 450 mg PiB VH4004280 Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB VH4004280 Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63. Part 3 (Single dose): VH4004280 450 mg tablet VH4004280 Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.
- Primary Outcome Measures
Name Time Method Part 3: Number of Participants With Any AEs and by Severity Up to Day 49 The DAIDS Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social \& functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social \& functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social \& functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.
Part 2: Number of Participants Discontinuing Treatment Due to AEs Up to Day 63 Number of participants who discontinued treatment due to AEs are presented.
Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity Up to Day 49 An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social \& functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social \& functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social \& functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.
Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin Up to Day 49 Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.
Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST Up to Day 63 Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST From Baseline (Day 1) and up to Day 49 Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST From Baseline (Day 1) and up to Day 63 Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters Up to Day 63 Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 \[mild\] to grade 4 \[potentially life-threatening\]) have been presented.
Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4004280 At Day 1 Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.
Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4004280 Day 1 to Day 49 Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.
Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin From Baseline (Day 1) and up to Day 49 Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.
Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin From Baseline (Day 1) and up to Day 63 Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.
Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters Up to Day 49 Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 \[mild\] to grade 4 \[potentially life-threatening\]) have been presented.
Part 2: Cmax Following Repeat Dose Administration of VH4004280 At Days 1 and 14 for Part 2 (MAD): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.
Part 2: Number of Participants With Any AEs and by Severity Up to Day 63 The DAIDS Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social \& functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social \& functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social \& functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.
Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin Up to Day 63 Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Standard Deviation (SD)=0.00000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.00000.
Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST Up to Day 49 Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters Up to Day 49 Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 \[mild\] to grade 4 \[potentially life-threatening\]) have been presented.
Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) Following Single Dose Administration of VH4004280 At Day 1 Blood samples were collected as assessed by protocol, at specific time points for pharmacokinetic (PK) analysis to determine AUC(0-inf). For AUC, a linear trapezoidal method was employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations. Geometric Coefficient of Variation was expressed in percentages.
Part 2: AUC Over a Dosing Interval From Time of Dosing to the Time of the Subsequent Dose (AUC[0-t]) Following Repeat Dose Administration of VH4004280 At Days 1 and 14 for Part 2 (MAD): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine AUC(0-t). For AUC, a linear trapezoidal method was employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations.
Part 2: T1/2 Following Repeat Dose Administration of VH4004280 Day 14 to Day 63 for Part 2 (MAD): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and Day 15 to Day 63 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.
Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Up to Day 49 Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin Up to Day 49 Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.
Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin From Baseline (Day 1) and up to Day 49 Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST From Baseline (Day 1) and up to Day 49 Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4004280 At Day 1 Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.
Part 2: Tmax Following Repeat Dose Administration of VH4004280 At Days 1 and 14 for Part 2 (MAD): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
GSK Investigational Site
🇺🇸Las Vegas, Nevada, United States
GSK Investigational Site🇺🇸Las Vegas, Nevada, United States