Study to Assess the Effect of Co-Administration of AZD9833 on the Pharmacokinetics of Midazolam, of Omeprazole, of Celecoxib and of Dabigatran Etexilate in Healthy Postmenopausal Female Volunteers

NCT ID: NCT05438303

Last Updated: 2023-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-13
• Study Completion Date: 2022-12-13

Brief Summary

This study will be a fixed sequence drug-drug interaction study in healthy postmenopausal females, conducted at multiple study sites

Detailed Description

Participants will be randomized to one of 3 treatment arms on Day 1 prior to Investigational Medicinal Product (IMP) administration:

• Arm A: single oral doses of midazolam and omeprazole administered together + repeated doses of AZD9833 .
• Arm B: single oral doses of dabigatran etexilate + single oral dose of AZD9833 .
• Arm C: single oral doses of celecoxib + repeated oral doses of AZD9833.

Each participant will be involved in the study for up to 7 to 8 weeks

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Arm A (midazolam and omeprazole)

Participants will receive single oral doses of midazolam and omeprazole together (Day 1 of Treatment Periods 1 and 3) and repeated doses of AZD9833 (Days 1 to 5 of Treatment Period 2 and Day 1 of Treatment Period 3)

Group Type: EXPERIMENTAL

Omeprazole

Intervention Type: DRUG

An Omeprazole capsule will be administered once on Day 1 of Treatment Periods 1 and 3; administered together with Midazolam

AZD9833

Intervention Type: DRUG

AZD9833 tablets will be administered orally once daily on Days 1 - Day 5 (Treatment Period 2) and Day 1 (Treatment Period 3) for participants recruited to Arms A and C and Day 1 for those in Arm B

Midazolam

Intervention Type: DRUG

Midazolam will be administered orally as a syrup once on Day 1 of Treatment Periods 1 and 3; administered together with Omeprazole

Arm B (Dabigatran etexilate)

Participants will receive single oral doses of dabigatran etexilate (Day 1 of Treatment Periods 1 and 2) and single oral dose of AZD9833 (Day 1 of Treatment Period 2)

Group Type: EXPERIMENTAL

Dabigatran Etexilate

Intervention Type: DRUG

A Dabigatran Etexilate capsule will be administered once on Day 1 of Treatment Periods 1 and 2

AZD9833

Intervention Type: DRUG

AZD9833 tablets will be administered orally once daily on Days 1 - Day 5 (Treatment Period 2) and Day 1 (Treatment Period 3) for participants recruited to Arms A and C and Day 1 for those in Arm B

Arm C (Celecoxib)

Participants will receive single oral doses of celecoxib (Day 1 of Treatment Periods 1 and 3) and repeated oral doses of AZD9833 (Days 1 to 5 of Treatment Period 2 and Day 1 of Treatment Period 3)

Group Type: EXPERIMENTAL

Celecoxib

Intervention Type: DRUG

A Celecoxib capsule will be administered once on Day 1 of Treatment Periods 1 and 3

AZD9833

Intervention Type: DRUG

AZD9833 tablets will be administered orally once daily on Days 1 - Day 5 (Treatment Period 2) and Day 1 (Treatment Period 3) for participants recruited to Arms A and C and Day 1 for those in Arm B

Interventions

Omeprazole

An Omeprazole capsule will be administered once on Day 1 of Treatment Periods 1 and 3; administered together with Midazolam

Intervention Type: DRUG

Dabigatran Etexilate

A Dabigatran Etexilate capsule will be administered once on Day 1 of Treatment Periods 1 and 2

Intervention Type: DRUG

Celecoxib

A Celecoxib capsule will be administered once on Day 1 of Treatment Periods 1 and 3

Intervention Type: DRUG

AZD9833

AZD9833 tablets will be administered orally once daily on Days 1 - Day 5 (Treatment Period 2) and Day 1 (Treatment Period 3) for participants recruited to Arms A and C and Day 1 for those in Arm B

Intervention Type: DRUG

Midazolam

Midazolam will be administered orally as a syrup once on Day 1 of Treatment Periods 1 and 3; administered together with Omeprazole

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy postmenopausal female participants aged 50 to 70 years with suitable veins for cannulation or repeated venipuncture.
• Participants must be postmenopausal by fulfilling the following criterion:
• Have a Body mass index (BMI) between 19 and 35 kg/m^2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive as measured at screening.
• Must agree to not use warfarin or phenytoin (and other coumarin-derived vitamin K antagonist anticoagulants) during study, and for 2 weeks after last administration of IMP.

Exclusion Criteria

• History of any clinically significant disease or disorder as described by the Investigator.
• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Use of systemic estrogen-containing hormone replacement therapy within 6 months prior to first dose in the study.
• Have taken any proton pump inhibitors (omeprazole, lansoprazole, esomeprazole, pantoprazole, etc.) within 14 days of beginning study treatment (ie, first administration of omeprazole in Arm A.
• Have taken any drug with enzyme-inducing properties such as St John's Wort within 3 weeks of screening.
• Presence of any contraindication to the probe substrates omeprazole, midazolam, dabigatran or celecoxib per the United States Package Insert.
• Any of the following signs or confirmation of COVID-19 infection:
• Subject has a positive RT-PCR test for SARS-CoV-2 prior to randomization.
• Clinical signs and symptoms consistent with COVID-19 (eg, fever, dry cough, dyspnea, sore throat, fatigue) or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or at randomization.
• Subject has been previously hospitalized with COVID-19 infection within the last 12 months.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Long Beach, California, United States

Research Site

Berlin, New Jersey, United States

Countries

United States

Other Identifiers

D8532C00004

Identifier Type: -

Identifier Source: org_study_id