Cystic FibrosisPhase 1NCT07283770
Evaluation of VX-581 in Healthy Participants and in Participants With Cystic Fibrosis
A Phase 1 study testing VX-581, D-IVA and TEZ in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 1 site in United States.
Trial 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 in healthy participants. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- VX-581, D-IVA and TEZ
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 152 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Dec 2025to 12 Jul 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Parts A, B, C:
- 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
- Part D:
- Confirmed diagnosis of CF
Who cannot join
- Parts A, B, C:
- 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
- Part D:
- History of clinically significant cirrhosis with or without portal hypertension.
- Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Altasciences - Kansas City
Overland Park, Kansas, 66212
About this study
Official title: A Phase 1 Study of VX-581 in Healthy Subjects and in Subjects With Cystic Fibrosis
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 in healthy participants. The study will also evaluate the safety, tolerability, and pharmacokinetics of VX-581 administered in combination with D-IVA with or without TEZ in participants with cystic fibrosis (CF).
Read the 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 in participants with CF. VX-581 will be administered alone and in combination with TEZ and D-IVA. The study consists of Screening Phase, Run-In Phase (CF only), 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.).
- Conditions
- Cystic Fibrosis
- Being tested
- VX-581, Placebo, D-IVA, TEZ, ELX/TEZ/IVA
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VX-581Drug
Suspension for Oral Administration.
PlaceboDrug
Suspension for Oral Administration.
D-IVADrug
Also called deutivacaftor, VX-561
Tablet for Oral Administration.
TEZDrug
Also called tezacaftor, VX-661
Tablet for Oral Administration.
ELX/TEZ/IVADrug
Also called VX-445/VX-661/VX-770, elexacaftor/tezacaftor/ivacaftor
Fixed dose combination (FDC) Tablets for Oral Administration.
VX-581Drug
Tablets for Oral Administration.
IVADrug
Also called VX-770, Ivacaftor
Tablet for Oral Administration.
| Study group | Role | What they receive |
|---|---|---|
| Part A: Single Ascending Dose | Experimental | Participants will be randomized to receive a single dose of VX-581. Receives: Drug: VX-581 |
| Placebo: Part A | Placebo comparator | Participants will be randomized to receive a single dose of placebo matched to VX-581. Receives: Drug: Placebo |
| Part B: Multiple Ascending Dose | Experimental | Participants will be randomized to receive multiple doses of VX-581. Receives: Drug: VX-581 |
| Placebo: Part B | Placebo comparator | Participants will be randomized to receive multiple doses of placebo matched to VX-581. Receives: 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. Receives: 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. Receives: Drug: Placebo; Drug: D-IVA; Drug: TEZ |
| Part D: VX-581 with TEZ/D-IVA or D-IVA in CF | Experimental | Participants with CF will enter a run-in period and receive ELX/TEZ/IVA. Following the run-in period participants will receive VX-581 in combination with TEZ/D-IVA or D-IVA in the treatment period. Following the treatment period, participants will enter a 14-day Washout Period and receive ELX/TEZ/IVA. (Part D will be open-label) Receives: Drug: D-IVA; Drug: TEZ; Drug: ELX/TEZ/IVA; Drug: VX-581; Drug: IVA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: 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)
Measured: 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)
Measured: From Day -1 up to Day 17
Part D: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: From Signing of Informed Consent up to Day 105
Secondary outcomes (9)
Part A: Maximum Observed Plasma Concentration (Cmax) of VX-581
Measured: 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
Measured: On Day 1
Part B: Cmax of VX-581
Measured: On Days 1, 7, and 10
Part B: AUC0-24h Post-Dose of VX-581
Measured: On Days 1, 7, and 10
Part C: Cmax of VX-581, TEZ (if administered), D-IVA and their Metabolite(s)
Measured: On Days 1, 7, and 10
Part C: AUC0-24h Post Dose of VX-581, TEZ (if administered), D-IVA and their Metabolite(s)
Measured: On Days 1, 7, and 10
Part D: Cmax of VX-581, TEZ (if administered), D-IVA and their Metabolite(s)
Measured: On Day 1 and Day 28
Part D: AUC0-24h Post Dose of VX-581, TEZ (if administered), D-IVA and their Metabolite(s)
Measured: On Day 1 and Day 28
Part D: Absolute Change in Sweat Chloride (SwCl)
Measured: From Baseline Up To Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2025
- Study start9 Dec 2025
- Primary completion12 Jul 2027 (estimated)
- Study completion12 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 152 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07283770
- Sponsor's protocol ID
- VX25-581-001
- Status last verified
- Oct 2026
- First submitted
- 4 Dec 2025
- Last updated
- 19 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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/
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of VX-581 in Healthy Subjects and in Subjects With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT07283770
- Acronym / sponsor ID
- VX25-581-001
- Conditions
- Cystic Fibrosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 152 participants (estimated)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 9 Dec 2025 (actual)
- Primary completion
- 12 Jul 2027 (estimated)
- Study completion
- 12 Jul 2027 (estimated)
- First posted
- 16 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 in healthy participants. The study will also evaluate the safety, tolerability, and pharmacokinetics of VX-581 administered in combination with D-IVA with or without TEZ in participants with cystic fibrosis (CF).
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 in participants with CF. VX-581 will be administered alone and in combination with TEZ and D-IVA. The study consists of Screening Phase, Run-In Phase (CF only), 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Part A: Single Ascending Dose | Experimental | Drug: VX-581Participants will be randomized to receive a single dose of VX-581. |
| Placebo: Part A | Placebo comparator | Drug: PlaceboParticipants will be randomized to receive a single dose of placebo matched to VX-581. |
| Part B: Multiple Ascending Dose | Experimental | Drug: VX-581Participants will be randomized to receive multiple doses of VX-581. |
| Placebo: Part B | Placebo comparator | Drug: PlaceboParticipants will be randomized to receive multiple doses of placebo matched to VX-581. |
| Part C: VX-581 with TEZ/D-IVA or D-IVA | Experimental | Drug: VX-581, Drug: D-IVA, Drug: TEZParticipants will be randomized to receive multiple doses VX-581 in combination with TEZ/D-IVA or D-IVA. |
| Placebo: Part C | Placebo comparator | Drug: Placebo, Drug: D-IVA, Drug: TEZParticipants will be randomized to receive placebo matched to VX-581 in combination with TEZ/D-IVA or D-IVA. |
| Part D: VX-581 with TEZ/D-IVA or D-IVA in CF | Experimental | Drug: D-IVA, Drug: TEZ, Drug: ELX/TEZ/IVA, Drug: VX-581, Drug: IVAParticipants with CF will enter a run-in period and receive ELX/TEZ/IVA. Following the run-in period participants will receive VX-581 in combination with TEZ/D-IVA or D-IVA in the treatment period. Following the treatment period, participants will enter a 14-day Washout Period and receive ELX/TEZ/IVA. (Part D will be open-label) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Parts A, B, C:
- Part D:
Key exclusion criteria (6 listed)
- Parts A, B, C:
- Part D:
- Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VX-581Suspension for Oral Administration. | Drug | Part A: Single Ascending Dose, Part B: Multiple Ascending Dose, Part C: VX-581 with TEZ/D-IVA or D-IVA |
| PlaceboSuspension for Oral Administration. | Drug | Placebo: Part A, Placebo: Part B, Placebo: Part C |
| D-IVAAlso: deutivacaftor, VX-561Tablet for Oral Administration. | Drug | Part C: VX-581 with TEZ/D-IVA or D-IVA, Part D: VX-581 with TEZ/D-IVA or D-IVA in CF, Placebo: Part C |
| TEZAlso: tezacaftor, VX-661Tablet for Oral Administration. | Drug | Part C: VX-581 with TEZ/D-IVA or D-IVA, Part D: VX-581 with TEZ/D-IVA or D-IVA in CF, Placebo: Part C |
| ELX/TEZ/IVAAlso: VX-445/VX-661/VX-770, elexacaftor/tezacaftor/ivacaftorFixed dose combination (FDC) Tablets for Oral Administration. | Drug | Part D: VX-581 with TEZ/D-IVA or D-IVA in CF |
| VX-581Tablets for Oral Administration. | Drug | Part D: VX-581 with TEZ/D-IVA or D-IVA in CF |
| IVAAlso: VX-770, IvacaftorTablet for Oral Administration. | Drug | Part D: VX-581 with TEZ/D-IVA or D-IVA in CF |
Primary outcome
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
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
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
Part D: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Signing of Informed Consent up to Day 105
9 secondary outcomes
Part A: Maximum Observed Plasma Concentration (Cmax) of VX-581
Time frame: 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
Part B: Cmax of VX-581
Time frame: On Days 1, 7, and 10
Part B: AUC0-24h Post-Dose of VX-581
Time frame: On Days 1, 7, and 10
Part C: Cmax of VX-581, TEZ (if administered), D-IVA and their Metabolite(s)
Time frame: On Days 1, 7, and 10
Part C: AUC0-24h Post Dose of VX-581, TEZ (if administered), D-IVA and their Metabolite(s)
Time frame: On Days 1, 7, and 10
Part D: Cmax of VX-581, TEZ (if administered), D-IVA and their Metabolite(s)
Time frame: On Day 1 and Day 28
Part D: AUC0-24h Post Dose of VX-581, TEZ (if administered), D-IVA and their Metabolite(s)
Time frame: On Day 1 and Day 28
Part D: Absolute Change in Sweat Chloride (SwCl)
Time frame: From Baseline Up To Day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
- Individual participant dataSharing planned: No. 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/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VX-581, D-IVA and TEZ in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Medical Information (617-341-6777, medicalinfo@vrtx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.