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

NCT05438303 | Completed Phase 1 FDA Drug

• 1 other identifier: D8532C00004
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Healthy Volunteers

Keywords

Drug-Drug interaction; Midazolam; Omeprazole; Dabigatran etexilate; Celecoxib; Postmenopausal; Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Area under plasma concentration time curve from zero to infinity (AUCinf) of midazolam, omeprazole, total dabigatran, and celecoxib

  The effects of AZD9833 will be evaluated in healthy postmenopausal female participants on the key pharmacokinetic (PK) variables of: - single-dose midazolam and omeprazole, administered together * single-dose dabigatran etexilate * single-dose celecoxib

  For Arm A: Day 1 to Day 2 (Period 1 and 3); For Arm B: Day 1 to Day 3 (Period 1 and 2) (Each Period is 4 days); For Arm C: Day 1 to Day 4 (Period 1 and 3) (For Arm A and C, Period 1 is for 5 days and Period 3 is for 4 days)

• Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of midazolam, omeprazole, total dabigatran, and celecoxib

  The effects of AZD9833 will be evaluated in healthy postmenopausal female participants on the key pharmacokinetic variables of: * single-dose midazolam and omeprazole, administered together * single-dose dabigatran etexilate * single-dose celecoxib

  For Arm A: Day 1 to Day 2 (Period 1 and 3); For Arm B: Day 1 to Day 3 (Period 1 and 2) (Each Period is 4 days); For Arm C: Day 1 to Day 4 (Period 1 and 3) (For Arm A and C, Period 1 is for 5 days and Period 3 is for 4 days)

• Maximum observed plasma concentration (Cmax) of midazolam, omeprazole, dabigatran etexilate and celecoxib

  The effects of AZD9833 will be evaluated in healthy postmenopausal female participants on the key pharmacokinetic variables of: * single-dose midazolam and omeprazole administered together * single-dose dabigatran etexilate * single-dose celecoxib

  For Arm A: Day 1 to Day 2 (Period 1 and 3); For Arm B: Day 1 to Day 3 (Period 1 and 2) (Each Period is 4 days); For Arm C: Day 1 to Day 4 (Period 1 and 3) (For Arm A and C, Period 1 is for 5 days and Period 3 is for 4 days)

Secondary Outcomes (14)

• Number of participants with Adverse Events (AEs)

  From Screening until Post study (5 to 7 days post final dose) (assessed up to 6 months)

• AUCinf for AZD9833 and free dabigatran

  For AZD9833 in Arm A: Day 1 and Day 2 (Period 3); For AZD9833 in Arm B: Day 1 and Day 2 (Period 2); For dabigatran: Day 1 to Day 3 (Period 1 and 2) (Each Period lasts for 4 days)

• AUClast for AZD9833 and free dabigatran

  For AZD9833 in Arm A: Day 1 and Day 2 (Period 3); For AZD9833 in Arm B: Day 1 and Day 2 (Period 2); For dabigatran: Day 1 to Day 3 (Period 1 and 2) (Each Period lasts for 4 days)

• Area under plasma concentration-time curve in the dose interval (AUCt) for AZD9833 and free dabigatran

  For AZD9833 in Arm A: Day 1 and Day 2 (Period 3); For AZD9833 in Arm B: Day 1 and Day 2 (Period 2); For dabigatran: Day 1 to Day 3 (Period 1 and 2) (Each Period lasts for 4 days)

• Cmax for AZD9833 and free dabigatran

  For AZD9833 in Arm A: Day 1 and Day 2 (Period 3); For AZD9833 in Arm B: Day 1 and Day 2 (Period 2); For dabigatran: Day 1 to Day 3 (Period 1 and 2) (Each Period lasts for 4 days)

Study Arms (3)

Arm A (midazolam and omeprazole)

EXPERIMENTAL

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)

Drug: AZD9833; Drug: Midazolam; Drug: Omeprazole

Arm B (Dabigatran etexilate)

EXPERIMENTAL

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)

Drug: AZD9833; Drug: Dabigatran Etexilate

Arm C (Celecoxib)

EXPERIMENTAL

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)

Drug: AZD9833; Drug: Celecoxib

Interventions

AZD9833 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 A (midazolam and omeprazole); Arm B (Dabigatran etexilate); Arm C (Celecoxib)

Midazolam DRUG

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

Arm A (midazolam and omeprazole)

Omeprazole DRUG

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

Arm A (midazolam and omeprazole)

Dabigatran Etexilate DRUG

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

Arm B (Dabigatran etexilate)

Celecoxib DRUG

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

Arm C (Celecoxib)

Eligibility Criteria

• Age: 50 Years - 70 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Long Beach, California, 90806, United States

Location

Research Site

Berlin, New Jersey, 08009, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

AZD9833; Midazolam; Omeprazole; Dabigatran; Celecoxib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Benzimidazoles; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Pyrazoles; Azoles

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2022
• First Posted: June 29, 2022
• Study Start: June 13, 2022
• Primary Completion: December 13, 2022
• Study Completion: December 13, 2022
• Last Updated: January 12, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

US (2)