A Phase 1, First-in-human Study of VX-433

NCT07584434 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: VX25-433-001
• Study Type: interventional
• Target: 118
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of VX-433 following single and multiple ascending doses, as well as to assess the effect of VX-433 on the PK of midazolam, bupropion, and hydroxybupropion.

Conditions

Narcolepsy Type 1 (NT1)

Outcome Measures

Primary Outcomes (6)

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

  From Day 1 up to Day 6

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

  From Day 1 up to Day 18

• Part C: Maximum Observed Plasma Concentration (Cmax) of Midazolam in the Absence and Presence of VX-433

  From Day 1 up to Day 22

• Part C: Maximum Observed Plasma Concentration (Cmax) of Bupropion and Hydroxybupropion in the Absence and Presence of VX-433

  From Day 1 up to Day 22

• Part C: Area Under the Concentration Versus Time Curve (AUC) of Midazolam in the Absence and Presence of VX-433

  From Day 1 up to Day 22

• Part C: Area Under the Concentration Versus Time Curve (AUC) of Bupropion and Hydroxybupropion in the Absence and Presence of VX-433

  From Day 1 up to Day 22

Secondary Outcomes (11)

• Part A: Maximum Observed Plasma Concentration (Cmax) of VX-433

  From Day 1 up to Day 6

• Part B: Maximum Observed Plasma Concentration (Cmax) of VX-433

  From Day 1 up to Day 18

• Part A: Area Under the Concentration Versus Time Curve (AUC) of VX-433

  From Day 1 up to Day 6

• Part B: Area Under the Concentration Versus Time Curve (AUC) of VX-433

  From Day 1 up to Day 18

• Part A: Time Required for Plasma Concentration of VX-433 to Reduce to Half (t1/2)

  From Day 1 up to Day 6

Study Arms (5)

Part A: Single Ascending Dose (SAD)

EXPERIMENTAL

Participants will be randomized to receive a single dose of VX-433.

Drug: VX-433

Part A: Placebo

PLACEBO COMPARATOR

Participants will be randomized to receive placebo matched to VX-433.

Drug: Placebo

Part B: Multiple Ascending Dose (MAD)

EXPERIMENTAL

Participants will be randomized to receive multiple doses of VX-433.

Drug: VX-433

Part B: Placebo

PLACEBO COMPARATOR

Participants will be randomized to receive placebo matched to VX-433.

Drug: Placebo

Part C: Drug Drug Interaction

EXPERIMENTAL

Participants will receive a single dose of midazolam and bupropion on Day 1 in Dosing Period 1, followed by VX-433 administration for 17 days (Days 5 through 21) and then midazolam and bupropion on Day 18 in Dosing Period 2. Part C will be open-label.

Drug: VX-433; Drug: Midazolam; Drug: Bupropion

Interventions

VX-433 DRUG

Suspension for Oral Administration

Part A: Single Ascending Dose (SAD); Part B: Multiple Ascending Dose (MAD); Part C: Drug Drug Interaction

Placebo DRUG

Suspension for Oral Administration

Part A: Placebo; Part B: Placebo

Midazolam DRUG

Syrup for Oral Administration

Part C: Drug Drug Interaction

Bupropion DRUG

Capsule for Oral Administration

Part C: Drug Drug Interaction

Eligibility Criteria

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

You may qualify if:

• Body mass index (BMI) of 18.0 to 30.0 kilogram per meter square (kg/m2), inclusive
• A total body weight of more than (\>) 50 kg
• Nonsmoker or ex-smoker for at least 3 months before screening with current nonsmoking status confirmed by urine or blood cotinine at screening

You may not qualify if:

• History of febrile illness or other acute illness that has not fully resolved within 14 days before the first dose of study drug
• Any condition possibly affecting drug absorption
• For female participants: of childbearing potential, pregnant, breastfeeding, or planning to become pregnant or donate ova during the study or within 90 days after last dose of study drug

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

MeSH Terms

Interventions

Midazolam; Bupropion

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Propiophenones; Ketones; Organic Chemicals

Central Study Contacts

Medical Information

CONTACT

617-341-6777; medicalinfo@vrtx.com

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: May 6, 2026
• First Posted: May 13, 2026
• Study Start: May 12, 2026
• Primary Completion (Estimated): March 5, 2027
• Study Completion (Estimated): March 5, 2027
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share