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

A Phase 1, Randomized, Double-blind, Placebo-controlled, Dose Escalation Study Evaluating Safety and Pharmacokinetics of VX-581 in Healthy Subjects

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of VX-581.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: VX-581; Drug: Placebo

Detailed Description

The study is being conducted to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of VX-581 in healthy participants and consists of Screening Phase, Treatment Phase and Safety Follow-up Phase. Note: 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.).

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Medical Information; Phone Number: 617-341-6777; Email: medicalinfo@vrtx.com

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Recruiting
      • Altasciences - Kansas City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

• 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

Key Exclusion Criteria:

• 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

Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Single Ascending Dose; Participants will be randomized to receive a single dose of VX-581.	Drug: VX-581; Suspension for Oral Administration.
Placebo Comparator: Placebo: Part A; Participants will be randomized to receive a single dose of placebo matched to VX-581.	Drug: Placebo; Suspension for Oral Administration.
Experimental: Part B: Multiple Ascending Dose; Participants will be randomized to receive multiple doses of VX-581.	Drug: VX-581; Suspension for Oral Administration.
Placebo Comparator: Placebo: Part B; Participants will be randomized to receive multiple doses of placebo matched to VX-581.	Drug: Placebo; Suspension for Oral Administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2025
• Primary Completion (Estimated): November 19, 2026
• Study Completion (Estimated): November 19, 2026

Study Registration Dates

• First Submitted: December 4, 2025
• First Submitted That Met QC Criteria: December 4, 2025
• First Posted (Actual): December 16, 2025

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis
• Other Study ID Numbers: VX25-581-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/our-science/clinical-trials-data-sharing/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No