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Healthy VolunteersPhase 1NCT05438303

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

A Phase 1 study testing AZD9833, Midazolam and Omeprazole in people with Healthy Volunteers, run by AstraZeneca at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 50 to 70 years, women onlyHealthy volunteers can take part
Conditions the study is for
Healthy Volunteers
What is being tested?
AZD9833, Midazolam and Omeprazole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
2 sitesUnited States
Study dates
13 Jun 2022to 13 Dec 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 70 years
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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 locations and contacts

2 sites in 1 country.

United States2 sites
  • Research Site

    Berlin, New Jersey, 08009

  • Research Site

    Long Beach, California, 90806

Other trials in United States

About this study

Official title: A Phase 1, Multi-center, Open-label, 3-arm, Fixed Sequence Study to Assess the Effect of Co-administration of AZD9833 on the Pharmacokinetics of Midazolam (CYP3A4/5 Substrate), of Omeprazole (CYP2C19 Substrate), of Celecoxib (CYP2C9 Substrate) and of Dabigatran Etexilate (P-gp Transporter Substrate) in Healthy Postmenopausal Female Volunteers

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

Read the 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

Being tested
AZD9833, Midazolam, Omeprazole, Dabigatran Etexilate, Celecoxib
Keywords
Drug-Drug interaction, Midazolam, Omeprazole, Dabigatran etexilate, Celecoxib, Postmenopausal, Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD9833Drug

    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

  • MidazolamDrug

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

  • OmeprazoleDrug

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

  • Dabigatran EtexilateDrug

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

  • CelecoxibDrug

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

Study groups in NCT05438303
Study groupRoleWhat they receive
Arm A (midazolam and omeprazole)ExperimentalParticipants 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)
Receives: Drug: AZD9833; Drug: Midazolam; Drug: Omeprazole
Arm B (Dabigatran etexilate)ExperimentalParticipants 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)
Receives: Drug: AZD9833; Drug: Dabigatran Etexilate
Arm C (Celecoxib)ExperimentalParticipants 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)
Receives: Drug: AZD9833; Drug: Celecoxib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 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)

  2. 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

    Measured: 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)

  3. 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

    Measured: 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)
  1. Number of participants with Adverse Events (AEs)

    The safety and tolerability of AZD9833, alone and in combination with midazolam, omeprazole, dabigatran etexilate, and celecoxib will be evaluated in healthy postmenopausal female participants.

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

  2. AUCinf for AZD9833 and free dabigatran

    AZD9833 PK and the effect of AZD9833 on the PK of dabigatran etexilate will be further characterized.

    Measured: 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)

  3. AUClast for AZD9833 and free dabigatran

    AZD9833 PK and the effect of AZD9833 on the PK of dabigatran etexilate, and will be further characterized.

    Measured: 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)

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

    AZD9833 PK and the effect of AZD9833 on the PK of dabigatran etexilate will be further characterized.

    Measured: 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)

  5. Cmax for AZD9833 and free dabigatran

    AZD9833 PK and the effect of AZD9833 on the PK of dabigatran etexilate will be further characterized

    Measured: 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)

  6. Time to reach maximum observed concentration (tmax) for AZD9833 and free dabigatran

    AZD9833 PK and the effect of AZD9833 on the PK of midazolam, omeprazole, dabigatran etexilate, and celecoxib will be further characterized.

    Measured: 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)

  7. Half-life associated with terminal slope of a semi-logarithmic concentration-time curve (t½λz) for AZD9833 and free dabigatran

    AZD9833 PK and the effect of AZD9833 on the PK of midazolam, omeprazole, dabigatran etexilate, and celecoxib will be further characterized.

    Measured: 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)

  8. Apparent total body clearance from plasma after extravascular administration (CL/F) for AZD9833 and free dabigatran

    AZD9833 PK and the effect of AZD9833 on the PK of midazolam, omeprazole, dabigatran etexilate, and celecoxib will be further characterized.

    Measured: 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)

  9. Apparent volume of distribution based on terminal phase (Vz/F) for AZD9833 and free dabigatran

    AZD9833 PK and the effect of AZD9833 on the PK of midazolam, omeprazole, dabigatran etexilate, and celecoxib will be further characterized.

    Measured: 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)

  10. tmax for midazolam, omeprazole, total dabigatran, and celecoxib

    AZD9833 PK and the effect of AZD9833 on the PK of midazolam, omeprazole, dabigatran etexilate, and celecoxib will be further characterized.

    Measured: 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)

  11. t½λz for midazolam, omeprazole, total dabigatran, and celecoxib

    AZD9833 PK and the effect of AZD9833 on the PK of midazolam, omeprazole, dabigatran etexilate, and celecoxib will be further characterized.

    Measured: 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)

  12. CL/F for midazolam, omeprazole, total dabigatran, and celecoxib

    AZD9833 PK and the effect of AZD9833 on the PK of midazolam, omeprazole, dabigatran etexilate, and celecoxib will be further characterized.

    Measured: 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)

  13. Vz/F for midazolam, omeprazole, total dabigatran, and celecoxib

    AZD9833 PK and the effect of AZD9833 on the PK of midazolam, omeprazole, dabigatran etexilate, and celecoxib will be further characterized.

    Measured: 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)

  14. Area under the plasma concentration-curve from zero to 24 hours post dose (AUC0-24) for celecoxib

    AZD9833 PK and the effect of AZD9833 on the PK of midazolam, omeprazole, dabigatran etexilate, and celecoxib will be further characterized.

    Measured: Day 1 to Day 4 (Period 1) (Period 1 lasts for 5 days) and Day 1 to Day 4 (Period 3) (Period 3 lasts for 4 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jun 2022
  2. Study start13 Jun 2022
  3. Primary completion13 Dec 2022
  4. Study completion13 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05438303
Sponsor's protocol ID
D8532C00004
Status last verified
Jan 2023
First submitted
19 May 2022
Last updated
12 Jan 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD9833, Midazolam and Omeprazole in people with Healthy Volunteers, run by AstraZeneca at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area under plasma concentration time curve from zero to infinity (AUCinf) of midazolam, omeprazole, total dabigatran, and celecoxib (time frame: 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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2023.

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