A Phase 1 Dose Escalation Study of VX-708 in Healthy Participants

NCT05518734 | Completed Phase 1 FDA Drug

• 1 other identifier: VX22-708-003
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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

Conditions

Pain

Outcome Measures

Primary Outcomes (5)

• Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Day 1 up to Day 30

• Part A: Safety and Tolerability as Assessed by Number of Participants With Clinically Meaningful Findings in Columbia Suicide Severity Rating Scale (C-SSRS) Responses

  Day 1 up to Day 30

• Part A: Continuous Pulse Oximetry Monitoring as assessed by oxygen saturation for Cohort A4

  Pre-dose up to 6 hours Post-dose

• Part A: Infusion Nurses Society (INS) Visual Infusion Phlebitis (VIP) Score Monitoring

  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

  Day 1 up to Day 16

Secondary Outcomes (4)

• 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

• 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: 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 B: Infusion Nurses Society (INS) Visual Infusion Phlebitis (VIP) Score

  Day 1 up to Day 30

Study Arms (4)

Part A: VX-708 (Cohort A1-A3)

EXPERIMENTAL

Participants will receive multiple doses of one of different dose levels of VX-708 under fasting condition.

Drug: VX-708

Part A: Placebo

PLACEBO COMPARATOR

Participants will receive placebo matched to VX-708.

Drug: Placebo

Part A: Midazolam With or Without VX-708 (Cohort A4)

EXPERIMENTAL

Participants will receive a single dose of Midazolam with or without VX-708 under fasting condition.

Drug: VX-708; Drug: Midazolam

Part B: VX-708 With Itraconazole

EXPERIMENTAL

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.

Drug: VX-708; Drug: Itraconazole

Interventions

VX-708 DRUG

Solution for intravenous (IV) administration.

Part A: Midazolam With or Without VX-708 (Cohort A4); Part A: VX-708 (Cohort A1-A3); Part B: VX-708 With Itraconazole

Itraconazole DRUG

Solution for oral administration.

Part B: VX-708 With Itraconazole

Midazolam DRUG

Solution for oral administration.

Part A: Midazolam With or Without VX-708 (Cohort A4)

Placebo DRUG

Placebo matched to VX-708 for IV administration.

Part A: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (1)

Celerion - Tempe

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Conditions

Pain

Interventions

Itraconazole; Midazolam

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2022
• First Posted: August 29, 2022
• Study Start: September 17, 2022
• Primary Completion: March 7, 2023
• Study Completion: March 7, 2023
• Last Updated: March 30, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)