Dose Escalation Study Evaluating the Safety and Pharmacokinetics of VX-581 in Healthy Participants

NCT07283770 | Recruiting Phase 1 FDA Drug

• 1 other identifier: VX25-581-001
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of single dose of VX-581 and multiple ascending doses of VX-581 alone and in combination with tezacaftor (TEZ)/deutivacaftor (D-IVA) or D-IVA for up to ten days.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (3)

• 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 8

• 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 17

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

  From Day -1 up to Day 17

Secondary Outcomes (6)

• Part A: Maximum Observed Plasma Concentration (Cmax) of VX-581

  On Day 1

• Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing Up to 24 Hours (AUC0-24h) Post-Dose of VX-581

  On Day 1

• Part B: Maximum Observed Plasma Concentration (Cmax) of VX-581

  On Days 1, 7, and 10

• Part B: Area Under the Concentration Versus Time Curve From the Time of Dosing Up to 24 Hours (AUC0-24h) Post-Dose of VX-581

  On Days 1, 7, and 10

• Part C: Maximum Observed Plasma Concentration (Cmax) of VX-581, TEZ (if administered), D-IVA and their Metabolite(s)

  On Days 1, 7, and 10

Study Arms (6)

Part A: Single Ascending Dose

EXPERIMENTAL

Participants will be randomized to receive a single dose of VX-581.

Drug: VX-581

Placebo: Part A

PLACEBO COMPARATOR

Participants will be randomized to receive a single dose of placebo matched to VX-581.

Drug: Placebo

Part B: Multiple Ascending Dose

EXPERIMENTAL

Participants will be randomized to receive multiple doses of VX-581.

Drug: VX-581

Placebo: Part B

PLACEBO COMPARATOR

Participants will be randomized to receive multiple doses of placebo matched to VX-581.

Drug: Placebo

Part C: VX-581 with TEZ/D-IVA or D-IVA

EXPERIMENTAL

Participants will be randomized to receive multiple doses VX-581 in combination with TEZ/D-IVA or D-IVA.

Drug: VX-581; Drug: D-IVA; Drug: TEZ

Placebo: Part C

PLACEBO COMPARATOR

Participants will be randomized to receive placebo matched to VX-581 in combination with TEZ/D-IVA or D-IVA.

Drug: Placebo; Drug: D-IVA; Drug: TEZ

Interventions

VX-581 DRUG

Suspension for Oral Administration.

Part A: Single Ascending Dose; Part B: Multiple Ascending Dose; Part C: VX-581 with TEZ/D-IVA or D-IVA

Placebo DRUG

Suspension for Oral Administration.

Placebo: Part A; Placebo: Part B; Placebo: Part C

D-IVA DRUG

Tablet for Oral Administration.

Also known as: deutivacaftor

Part C: VX-581 with TEZ/D-IVA or D-IVA; Placebo: Part C

TEZ DRUG

Tablet for Oral Administration.

Also known as: tezacaftor

Part C: VX-581 with TEZ/D-IVA or D-IVA; Placebo: Part C

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 32.0 kilogram per meter square (kg/m\^2)
• A total body weight of more than (\>) 50 kg
• Male and Female participants of non-childbearing potential

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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (1)

Altasciences - Kansas City

Overland Park, Kansas, 66212, United States

RECRUITING

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

deutivacaftor, tezacaftor , vanzacaftor; tezacaftor

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2025
• First Posted: December 16, 2025
• Study Start: December 9, 2025
• Primary Completion (Estimated): November 19, 2026
• Study Completion (Estimated): November 19, 2026
• Last Updated: July 16, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)