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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Celecoxib; Drug: AZD9833; Drug: Dabigatran Etexilate; Drug: Omeprazole; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT05438303

D8532C00004

Details and patient eligibility

About

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

Full 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

Enrollment: 59 patients

Sex: Female

Ages: 50 to 70 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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59 participants in 3 patient groups

Arm A (midazolam and omeprazole)

Experimental group

Description:

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)

Treatment:

Drug: Midazolam

Drug: AZD9833

Drug: Omeprazole

Arm B (Dabigatran etexilate)

Experimental group

Description:

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)

Treatment:

Drug: AZD9833

Drug: Dabigatran Etexilate

Arm C (Celecoxib)

Experimental group

Description:

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)

Treatment:

Drug: Celecoxib

Drug: AZD9833