- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04545944
Evaluation of Effect of Vonoprazan on Midazolam Pharmacokinetics in Healthy Participants
June 6, 2022 updated by: Phathom Pharmaceuticals, Inc.
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.).
Study Type
Interventional
Enrollment (Actual)
20
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 Locations
-
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Texas
-
Austin, Texas, United States, 78744
- PPD Development, LP
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-
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
18 years to 45 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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).
- 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.
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: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Midazolam single doses / Vonoprazan multiple doses
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
|
20 mg tablets administered orally
2 mg syrup administered orally
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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
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.
|
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
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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.
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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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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)
September 15, 2020
Primary Completion (Actual)
November 13, 2020
Study Completion (Actual)
November 25, 2020
Study Registration Dates
First Submitted
September 4, 2020
First Submitted That Met QC Criteria
September 4, 2020
First Posted (Actual)
September 11, 2020
Study Record Updates
Last Update Posted (Actual)
March 17, 2023
Last Update Submitted That Met QC Criteria
June 6, 2022
Last Verified
June 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Tranquilizing Agents
- Psychotropic Drugs
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Midazolam
Other Study ID Numbers
- VONO-101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
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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