Narcolepsy Type 1 (NT1)Phase 1NCT07584434
A Phase 1, First-in-human Study of VX-433
A Phase 1 study testing VX-433, Midazolam and Bupropion in people with Narcolepsy Type 1 (NT1), 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 (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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Narcolepsy Type 1 (NT1)
- What is being tested?
- VX-433, Midazolam and Bupropion
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 118 participants
- Where
- 1 siteUnited States
- Study dates
- 21 May 2026to 5 Mar 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
- 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
Who cannot join
- 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
- Other protocol defined Inclusion/Exclusion criteria will 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
ICON - Utah - Salt Lake City Office
Salt Lake City, Utah, 84124
About this study
Official title: A Phase 1, First-in-human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of VX-433 and Its Effects on the Pharmacokinetics of Midazolam and Bupropion
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.
Read the detailed description
The study is being conducted in healthy participants to evaluate the safety, tolerability, and PK of VX-433 (Parts A and B), as well as potential drug-drug interaction (DDI) between VX-433 and midazolam or bupropion (Part C).
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
- Narcolepsy Type 1 (NT1)
- Being tested
- VX-433, Placebo, Midazolam, Bupropion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VX-433Drug
Suspension for Oral Administration
PlaceboDrug
Suspension for Oral Administration
MidazolamDrug
Syrup for Oral Administration
BupropionDrug
Capsule for Oral Administration
| Study group | Role | What they receive |
|---|---|---|
| Part A: Single Ascending Dose (SAD) | Experimental | Participants will be randomized to receive a single dose of VX-433. Receives: Drug: VX-433 |
| Part A: Placebo | Placebo comparator | Participants will be randomized to receive placebo matched to VX-433. Receives: Drug: Placebo |
| Part B: Multiple Ascending Dose (MAD) | Experimental | Participants will be randomized to receive multiple doses of VX-433. Receives: Drug: VX-433 |
| Part B: Placebo | Placebo comparator | Participants will be randomized to receive placebo matched to VX-433. Receives: 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. Receives: Drug: VX-433; Drug: Midazolam; Drug: Bupropion |
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 6
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 18
Part C: Maximum Observed Plasma Concentration (Cmax) of Midazolam in the Absence and Presence of VX-433
Measured: 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
Measured: 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
Measured: 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
Measured: From Day 1 up to Day 22
Secondary outcomes (11)
Part A: Maximum Observed Plasma Concentration (Cmax) of VX-433
Measured: From Day 1 up to Day 6
Part B: Maximum Observed Plasma Concentration (Cmax) of VX-433
Measured: From Day 1 up to Day 18
Part A: Area Under the Concentration Versus Time Curve (AUC) of VX-433
Measured: From Day 1 up to Day 6
Part B: Area Under the Concentration Versus Time Curve (AUC) of VX-433
Measured: From Day 1 up to Day 18
Part A: Time Required for Plasma Concentration of VX-433 to Reduce to Half (t1/2)
Measured: From Day 1 up to Day 6
Part B: Time Required for Plasma Concentration of VX-433 to Reduce to Half (t1/2)
Measured: From Day 1 up to Day 18
Part A: Renal Clearance (CLr) of VX-433
Measured: From Day 1 up to Day 2
Part B: Renal Clearance (CLr) of VX-433
Measured: From Day 1 up to Day 11
Part A: Amount of VX-433 excreted in Urine
Measured: From Day 1 up to Day 2
Part B: Amount of VX-433 excreted in Urine
Measured: From Day 1 up to Day 11
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 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2026
- Study start21 May 2026
- Primary completion5 Mar 2027 (estimated)
- Study completion5 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Narcolepsy Type 1 (NT1)Studies 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
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 118 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
- NCT07584434
- Sponsor's protocol ID
- VX25-433-001
- Status last verified
- May 2026
- First submitted
- 6 May 2026
- Last updated
- 8 Jun 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 8 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, First-in-human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of VX-433 and Its Effects on the Pharmacokinetics of Midazolam and Bupropion
- ClinicalTrials.gov ID
- NCT07584434
- Acronym / sponsor ID
- VX25-433-001
- Conditions
- Narcolepsy Type 1 (NT1)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 118 participants (estimated)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 21 May 2026 (actual)
- Primary completion
- 5 Mar 2027 (estimated)
- Study completion
- 5 Mar 2027 (estimated)
- First posted
- 13 May 2026 (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 (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.
Detailed description
The study is being conducted in healthy participants to evaluate the safety, tolerability, and PK of VX-433 (Parts A and B), as well as potential drug-drug interaction (DDI) between VX-433 and midazolam or bupropion (Part C).
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
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part A: Single Ascending Dose (SAD) | Experimental | Drug: VX-433Participants will be randomized to receive a single dose of VX-433. |
| Part A: Placebo | Placebo comparator | Drug: PlaceboParticipants will be randomized to receive placebo matched to VX-433. |
| Part B: Multiple Ascending Dose (MAD) | Experimental | Drug: VX-433Participants will be randomized to receive multiple doses of VX-433. |
| Part B: Placebo | Placebo comparator | Drug: PlaceboParticipants will be randomized to receive placebo matched to VX-433. |
| Part C: Drug Drug Interaction | Experimental | Drug: VX-433, Drug: Midazolam, Drug: BupropionParticipants 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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
- Other protocol defined Inclusion/Exclusion criteria will 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-433Suspension for Oral Administration | Drug | Part A: Single Ascending Dose (SAD), Part B: Multiple Ascending Dose (MAD), Part C: Drug Drug Interaction |
| PlaceboSuspension for Oral Administration | Drug | Part A: Placebo, Part B: Placebo |
| MidazolamSyrup for Oral Administration | Drug | Part C: Drug Drug Interaction |
| BupropionCapsule for Oral Administration | Drug | Part C: Drug Drug Interaction |
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 6
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 18
Part C: Maximum Observed Plasma Concentration (Cmax) of Midazolam in the Absence and Presence of VX-433
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From Day 1 up to Day 22
11 secondary outcomes
Part A: Maximum Observed Plasma Concentration (Cmax) of VX-433
Time frame: From Day 1 up to Day 6
Part B: Maximum Observed Plasma Concentration (Cmax) of VX-433
Time frame: From Day 1 up to Day 18
Part A: Area Under the Concentration Versus Time Curve (AUC) of VX-433
Time frame: From Day 1 up to Day 6
Part B: Area Under the Concentration Versus Time Curve (AUC) of VX-433
Time frame: From Day 1 up to Day 18
Part A: Time Required for Plasma Concentration of VX-433 to Reduce to Half (t1/2)
Time frame: From Day 1 up to Day 6
Part B: Time Required for Plasma Concentration of VX-433 to Reduce to Half (t1/2)
Time frame: From Day 1 up to Day 18
Part A: Renal Clearance (CLr) of VX-433
Time frame: From Day 1 up to Day 2
Part B: Renal Clearance (CLr) of VX-433
Time frame: From Day 1 up to Day 11
Part A: Amount of VX-433 excreted in Urine
Time frame: From Day 1 up to Day 2
Part B: Amount of VX-433 excreted in Urine
Time frame: From Day 1 up to Day 11
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 29
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 8 Jun 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-433, Midazolam and Bupropion in people with Narcolepsy Type 1 (NT1), 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 3 inclusion and 4 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 8 Jun 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 6). The study lists 6 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 8 Jun 2026.