A Phase 1, Randomized, Double-blind, Placebo-controlled, Multiple-dose Escalation Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of VX-708 in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- VX-708
- Conditions
- Pain
- Sponsor
- Vertex Pharmaceuticals Incorporated
- Enrollment
- 64
- Locations
- 1
- Primary Endpoint
- Part A: Safety and Tolerability as Assessed by Number of Participants With Clinically Meaningful Findings in Columbia Suicide Severity Rating Scale (C-SSRS) Responses
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety, pharmacokinetics, and pharmacodynamics of multiple ascending doses of VX-708 in healthy participants
Detailed Description
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female of non-childbearing potential are eligible
- •Body mass index (BMI) of 18.0 to 32.0 kilograms per meter square (kg/m\^2)
- •A total body weight greater than (\>) 50 kg
Exclusion Criteria
- •History of febrile illness or other acute illness within 14 days before the first dose of study drug
- •History of cardiac dysrhythmias
- •Part A Cohorts with Midazolam DDI Evaluation (Cohort A4) Only
- •Hypersensitivity to midazolam or benzodiazepines
- •Part A Cohorts with CSF Sampling (Cohorts A2 and A3) Only
- •Hypersensitivity to local anesthetic for lumbar puncture
- •History of conditions leading to increased intracranial pressure (e.g., brain tumor, idiopathic intracranial hypertension, venous sinus thrombosis)
- •Part B Only
- •Hypersensitivity to itraconazole
- •Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
Part A: VX-708 (Cohort A1-A3)
Participants will receive multiple doses of one of different dose levels of VX-708 under fasting condition.
Intervention: VX-708
Part A: Placebo
Participants will receive placebo matched to VX-708.
Intervention: Placebo
Part A: Midazolam With or Without VX-708 (Cohort A4)
Participants will receive a single dose of Midazolam with or without VX-708 under fasting condition.
Intervention: VX-708
Part A: Midazolam With or Without VX-708 (Cohort A4)
Participants will receive a single dose of Midazolam with or without VX-708 under fasting condition.
Intervention: Midazolam
Part B: VX-708 With Itraconazole
Participants will receive a single dose of VX-708 in treatment period 1, followed by itraconazole, which will be dosed daily with a single dose of VX-708 administered in treatment period 2 under fasting conditions. A washout period of 6 days will be maintained between the 2 treatment periods.
Intervention: VX-708
Part B: VX-708 With Itraconazole
Participants will receive a single dose of VX-708 in treatment period 1, followed by itraconazole, which will be dosed daily with a single dose of VX-708 administered in treatment period 2 under fasting conditions. A washout period of 6 days will be maintained between the 2 treatment periods.
Intervention: Itraconazole
Outcomes
Primary Outcomes
Part A: Safety and Tolerability as Assessed by Number of Participants With Clinically Meaningful Findings in Columbia Suicide Severity Rating Scale (C-SSRS) Responses
Time Frame: Day 1 up to Day 30
Part A: Continuous Pulse Oximetry Monitoring as assessed by oxygen saturation for Cohort A4
Time Frame: Pre-dose up to 6 hours Post-dose
Part A: Infusion Nurses Society (INS) Visual Infusion Phlebitis (VIP) Score Monitoring
Time Frame: Day 1 up to Day 30
Part B: Area Under the Plasma Concentration Versus Time Curve from the Time of Dosing Extrapolated to Infinity (AUC0-inf) of VX-708 in the Absence or Presence of Itraconazole
Time Frame: Day 1 up to Day 16
Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Day 1 up to Day 30
Secondary Outcomes
- Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Day 1 up to Day 32)
- Part A: Area Under the Concentration Versus Time Curve from the Time of Dosing Extrapolated to Infinity (AUC0-inf) of Midazolam and 1-hydroxy-midazolam in the Absence or Presence of VX-708 (Cohort A4)(Day 1 up to Day 14)
- Part B: Infusion Nurses Society (INS) Visual Infusion Phlebitis (VIP) Score(Day 1 up to Day 30)
- Part A: Area Under the Plasma Concentration Versus Time Curve from the Time of Dosing Extrapolated to Infinity (AUC0-inf) of VX-708(Day 1 up to Day 14)