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

July 14, 2026 updated by: Vertex Pharmaceuticals Incorporated

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 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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. Additionally, VX-581 will also be administered in combination with tezacaftor (TEZ)/deutivacaftor (D-IVA) or D-IVA for up to ten days. 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)

136

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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.
Experimental: Part C: VX-581 with TEZ/D-IVA or D-IVA
Participants will be randomized to receive multiple doses VX-581 in combination with TEZ/D-IVA or D-IVA.
Drug: VX-581
Suspension for Oral Administration.
Drug: D-IVA
Tablet for Oral Administration.
Other Names:
  • deutivacaftor
Drug: TEZ
Tablet for Oral Administration.
Other Names:
  • tezacaftor
Placebo Comparator: Placebo: Part C
Participants will be randomized to receive placebo matched to VX-581 in combination with TEZ/D-IVA or D-IVA.
Drug: Placebo
Suspension for Oral Administration.
Drug: D-IVA
Tablet for Oral Administration.
Other Names:
  • deutivacaftor
Drug: TEZ
Tablet for Oral Administration.
Other Names:
  • tezacaftor

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)
Time Frame: From Day -1 up to Day 8
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)
Time Frame: From Day -1 up to Day 17
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)
Time Frame: From Day -1 up to Day 17
From Day -1 up to Day 17

Secondary Outcome Measures

Outcome Measure
Time Frame
Part A: Maximum Observed Plasma Concentration (Cmax) of VX-581
Time Frame: On Day 1
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
Time Frame: On Day 1
On Day 1
Part B: Maximum Observed Plasma Concentration (Cmax) of VX-581
Time Frame: On Days 1, 7, and 10
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
Time Frame: On Days 1, 7, and 10
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)
Time Frame: On Days 1, 7, and 10
On Days 1, 7, and 10
Part C: Area Under the Concentration Versus Time Curve From the Time of Dosing Up to 24 Hours (AUC0-24h) Post Dose of VX-581, TEZ (if administered), D-IVA and their Metabolite(s)
Time Frame: On Days 1, 7, and 10
On Days 1, 7, and 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vertex Pharmaceuticals Incorporated

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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)

July 16, 2026

Last Update Submitted That Met QC Criteria

July 14, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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