Evaluation of Effect of Vonoprazan on Midazolam Pharmacokinetics in Healthy Participants

NCT04545944 | Completed Phase 1 Results FDA Drug

• 1 other identifier: VONO-101
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Keywords

vonoprazan; midazolam

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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

Study Arms (1)

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

Drug: Vonoprazan; Drug: Midazolam

Interventions

Vonoprazan DRUG

20 mg tablets administered orally

Midazolam single doses / Vonoprazan multiple doses

Midazolam DRUG

2 mg syrup administered orally

Midazolam single doses / Vonoprazan multiple doses

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Phathom Pharmaceuticals, Inc.: lead

Study Sites (1)

PPD Development, LP

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Phathom Medical Information
• Organization: Phathom Pharmaceuticals, Inc.

medicalinformation@phathompharma.com

1-888-775-PHAT (7428)

Study Officials

• Medical Director

  Phathom Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2020
• First Posted: September 11, 2020
• Study Start: September 15, 2020
• Primary Completion: November 13, 2020
• Study Completion: November 25, 2020
• Last Updated: March 17, 2023
• Results First Posted: March 17, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)