Healthy VolunteersPhase 1NCT04545944

Evaluation of Effect of Vonoprazan on Midazolam Pharmacokinetics in Healthy Participants

A Phase 1 study testing Vonoprazan and Midazolam in people with Healthy Volunteers, run by Phathom Pharmaceuticals, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To determine the time-dependent inhibition potential of repeated doses of oral vonoprazan on the pharmacokinetics (PK) of a single oral dose of midazolam, a sensitive cytochrome P450 3A4 (CYP3A4) substrate, in healthy participants. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: Vonoprazan and Midazolam
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteUnited States
Study dates: 15 Sep 2020to 25 Nov 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

The participant is male or female 18 to 45 years of age, inclusive, at Screening.
The participant has a body mass index (BMI) 18 to 30 kg/m2, inclusive, and body weight >50 kg at Screening.
The participant is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at Screening.
Female participants of childbearing potential who may be sexually active with a non-sterilized male partner must use an acceptable method of birth control (ie, diaphragm with spermicide, intrauterine device, condom with foam or vaginal spermicide, oral contraceptives, or abstinence) from the signing of informed consent until 4 weeks after the last dose of study drug or be surgically sterile (ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or postmenopausal (defined as amenorrhea for 12 consecutive months and documented plasma follicle-stimulating hormone [FSH] level >40 IU/mL).
Female participants must have a negative pregnancy test at Screening and Check-in.
The participant agrees to comply with all protocol requirements.
The participant is able to provide written informed consent.

Who cannot join

The participant has a history of any clinically significant neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, hematological, or endocrine disease or other abnormality that may affect the ability of the subject to participate in the study.
The participant has a positive test result for coronavirus disease 2019 (COVID-19), hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus type 1 or 2 antibodies at Screening.
The participant has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × the upper limit of normal (ULN) or total bilirubin >1.5 × ULN (with the exception of Gilbert's syndrome) at Screening or Check-in.
The participant has serum creatinine >1.2 mg/dL or blood urea nitrogen >20 mg/dL at Screening or Check-in.
The participant has any acute laboratory abnormality at Screening that precludes participation in the study, in the opinion of the investigator.
The participant has a current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome and asymptomatic gallstones).

Show all 19Show fewer

The subject has used any prescription (excluding hormonal birth control) or over-the-counter medications (including CYP3A4 inducers) except paracetamol (up to 2 g per day), including herbal or nutritional supplements, within 14 days (or 5 half-lives) before the first dose of study drug or throughout the study.
The subject has consumed grapefruit or grapefruit juice, Seville orange or Seville orange-containing products (eg, marmalade), or food products that may be CYP3A4 inhibitors (eg, vegetables from the mustard green family [kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard] and charbroiled meats) within 7 days (or 5 half-lives) before the first dose of study drug or throughout the study.
The subject has consumed caffeine or xanthine-containing products within 48 hours (or 5 half-lives) before the first dose of study drug or throughout the study.
The subject is a smoker or has used nicotine or nicotine-containing products (eg, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 6 months before the first dose of study drug.
The subject has a history of alcohol abuse or drug addiction within the last year, excessive alcohol consumption (regular alcohol intake >21 units per week for male subjects and >14 units of alcohol per week for female subjects; 1 unit is equal to approximately 1/2 pint [200 mL] of beer, 1 small glass [100 mL] of wine, or 1 measure.
The subject has a positive test result for drugs of abuse, alcohol, or cotinine (indicating active current smoking) at Screening or Check-in.
The subject is involved in strenuous activity or contact sports within 24 hours before the first dose of study drug or throughout the study.
The subject has donated blood or blood products >450 mL within 30 days before the first dose of study drug.
The subject has a history of relevant drug and/or food allergies (ie, allergy to midazolam, vonoprazan, or their excipients [including cherries] or any significant food allergy that could preclude a standard diet in the clinical unit).
The subject has received study drug in another investigational study within 30 days of dosing.
Female subject is pregnant or lactating, intends to become pregnant before, during, or within 4 weeks after participating in this study, or intends to donate ova during this time period.
The subject has a history of acute narrow-angle glaucoma.
In the opinion of the investigator, the subject is not suitable for entry into the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

PPD Development, LP
Austin, Texas, 78744

Other trials in United States

About this study

Official title: An Open-Label, Fixed Sequence, Clinical Drug Interaction Study to Evaluate the Time-Dependent Inhibition Potential of Vonoprazan on a Sensitive CYP3A4 Substrate, Midazolam, in Healthy Volunteers

Read the detailed description

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: Healthy Volunteers
Being tested: Vonoprazan, Midazolam
Keywords: vonoprazan, midazolam

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VonoprazanDrug
20 mg tablets administered orally
MidazolamDrug
2 mg syrup administered orally

Study groups in NCT04545944
Study group	Role	What they receive
Midazolam single doses / Vonoprazan multiple doses	Experimental	Single oral doses of 2 mg of midazolam syrup on Day 1 and Day 9 and twice daily (BID) doses of 20 mg vonoprazan oral tablets on Days 2 through 10 Receives: Drug: Vonoprazan; Drug: Midazolam

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Midazolam
AUC0-t was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.
Measured: Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam
AUC0-inf was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.
Measured: Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Midazolam
Cmax was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.
Measured: Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Sep 202025 Nov 2020

First posted11 Sep 2020
Study start15 Sep 2020
Primary completion13 Nov 2020
Study completion25 Nov 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04545944
Sponsor's protocol ID: VONO-101
Status last verified: Jun 2022
First submitted: 4 Sep 2020
Last updated: 17 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 17 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label, Fixed Sequence, Clinical Drug Interaction Study to Evaluate the Time-Dependent Inhibition Potential of Vonoprazan on a Sensitive CYP3A4 Substrate, Midazolam, in Healthy Volunteers
ClinicalTrials.gov ID: NCT04545944
Acronym / sponsor ID: VONO-101
Conditions: Healthy Volunteers
Keywords: vonoprazan, midazolam
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: Phathom Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 15 Sep 2020 (actual)
Primary completion: 13 Nov 2020 (actual)
Study completion: 25 Nov 2020 (actual)
First posted: 11 Sep 2020 (actual)
Results: Posted 17 Mar 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Midazolam single doses / Vonoprazan multiple doses	Experimental	Drug: Vonoprazan, Drug: MidazolamSingle oral doses of 2 mg of midazolam syrup on Day 1 and Day 9 and twice daily (BID) doses of 20 mg vonoprazan oral tablets on Days 2 through 10

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

The participant is male or female 18 to 45 years of age, inclusive, at Screening.
The participant has a body mass index (BMI) 18 to 30 kg/m2, inclusive, and body weight >50 kg at Screening.
The participant is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at Screening.
Female participants of childbearing potential who may be sexually active with a non-sterilized male partner must use an acceptable method of birth control (ie, diaphragm with spermicide, intrauterine device, condom with foam or vaginal spermicide, oral contraceptives, or abstinence) from the signing of informed consent until 4 weeks after the last dose of study drug or be surgically sterile (ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or postmenopausal (defined as amenorrhea for 12 consecutive months and documented plasma follicle-stimulating hormone [FSH] level >40 IU/mL).
Female participants must have a negative pregnancy test at Screening and Check-in.

Key exclusion criteria (19 listed)

The participant has a history of any clinically significant neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, hematological, or endocrine disease or other abnormality that may affect the ability of the subject to participate in the study.
The participant has a positive test result for coronavirus disease 2019 (COVID-19), hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus type 1 or 2 antibodies at Screening.
The participant has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × the upper limit of normal (ULN) or total bilirubin >1.5 × ULN (with the exception of Gilbert's syndrome) at Screening or Check-in.
The participant has serum creatinine >1.2 mg/dL or blood urea nitrogen >20 mg/dL at Screening or Check-in.
The participant has any acute laboratory abnormality at Screening that precludes participation in the study, in the opinion of the investigator.

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
Vonoprazan20 mg tablets administered orally	Drug	Midazolam single doses / Vonoprazan multiple doses
Midazolam2 mg syrup administered orally	Drug	Midazolam single doses / Vonoprazan multiple doses

Primary outcome

Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Midazolam
Time frame: Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose
AUC0-t was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam
Time frame: Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose
AUC0-inf was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.
Maximum Observed Plasma Concentration (Cmax) of Midazolam
Time frame: Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose
Cmax was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.

Results and safety

Results posted to the registry on 17 Mar 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Participants	20	20

Primary outcome: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Midazolam

Time frame: Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose. Mean (Standard Deviation). Unit: Nanogram Hours per Milliliter (ng•h/mL)

Measure	Midazolam Alone n = 20	Midazolam With Vonoprazan n = 20
Value	24.2 (8.76)	50.7 (39.8)

Midazolam Alone vs Midazolam With Vonoprazan: Geometric Least Squares Mean Ratio: 192.4 (90% CI 152.8 to 242.4)

Population analysed: The pharmacokinetics (PK) population included participants who received at least one dose of study drug and had sufficient concentration data to support accurate estimation of at least one PK parameter. Participants who experienced vomiting within two times the median time to maximum observed plasma concentration (Tmax) after midazolam dosing were excluded from the PK analysis.

Primary outcome: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam

Measure	Midazolam Alone n = 20	Midazolam With Vonoprazan n = 20
Value	25.5 (9.00)	52.3 (39.8)

Midazolam Alone vs Midazolam With Vonoprazan: Geometric Least Squares Mean Ratio: 188.9 (90% CI 150.6 to 236.9)

Population analysed: The PK population included participants who received at least one dose of study drug and had sufficient concentration data to support accurate estimation of at least one PK parameter. Participants who experienced vomiting within two times the median time to maximum observed plasma concentration (Tmax) after midazolam dosing were excluded from the PK analysis.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Midazolam

Measure	Midazolam Alone n = 20	Midazolam With Vonoprazan n = 20
Value	10.3 (3.61)	20.3 (9.55)

Midazolam Alone vs Midazolam With Vonoprazan: Geometric Least Squares Mean Ratio: 193.4 (90% CI 160.5 to 233.1)

Adverse events

Time frame: Day 1 to Day 25. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Midazolam Alone	0 of 20 (0%)	0 of 20 (0%)	0 of 20
Vonoprazan Alone	0 of 20 (0%)	4 of 20 (20%)	0 of 20
Midazolam With Vonoprazan	0 of 20 (0%)	2 of 20 (10%)	0 of 20

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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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. This study is not recruiting at the moment.

Medical Director study director

Phathom Pharmaceuticals, Inc.

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 Vonoprazan and Midazolam in people with Healthy Volunteers, run by Phathom Pharmaceuticals, Inc. 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 7 inclusion and 19 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: finished, as of the sponsor's last update on 17 Mar 2023. 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. 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?

Yes. Results are posted in the registry (first posted 17 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Midazolam (time frame: Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04545944.

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 17 Mar 2023.