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The main purpose of the study is to assess the effect of multiple doses of baxdrostat on the pharmacokinetics (PK) of a single dose of combined oral ethinyl estradiol (EE) and levonorgestrel (LNG). Safety and tolerability of baxdrostat will be assessed during the study.
This is an open-label, 3-period fixed sequence study conducted at a single Clinical Unit.
The study will comprise of:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Period 1: Ethinyl estradiol/Levonorgestrel (EE/LNG) | Experimental | Participants will receive oral dose of EE/LNG in the fasted state on Day ,1 followed by PK sampling of EE/LNG for 120 hours (EE 72 hours and LNG 120 hours). |
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| Period 2: Baxdrostat | Experimental | Participants will self-administer the baxdrostat tablet once a day from Day 6 to Day 16. |
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| Period 3: Baxdrostat + EE/LNG | Experimental | Participants will receive baxdrostat once daily on Day 17 to Day 22 and will receive EE+LNG in the fasted state on Day 18, followed by oral dose of EE/LNG PK sampling for 120 hours (EE=72 hours and LNG=120 hours). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EE/LNG | Drug | EE/LNG tablet will be administered orally. |
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| Measure | Description | Time Frame |
|---|---|---|
| Area under concentration-time curve from time zero to infinity (AUCinf) | To assess the effect of multiple doses of baxdrostat on the PK of a single dose of combined oral EE/LNG in healthy females of non-childbearing potential. | EE: Up to Day 21, LNG: Up to Day 23 |
| Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) | To assess the effect of multiple doses of baxdrostat on the PK of a single dose of combined oral EE/LNG in healthy females of non-childbearing potential. | EE: Up to Day 21, LNG: Up to Day 23 |
| Maximum observed drug concentration (Cmax) | To assess the effect of multiple doses of baxdrostat on the PK of a single dose of combined oral EE/LNG in healthy females of non-childbearing potential. | EE: Up to Day 21, LNG: Up to Day 23 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum observed drug concentration (Cmax) of EE/LNG | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. | EE: Up to Day 21, LNG: Up to Day 23 |
| Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of EE/LNG |
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Inclusion Criteria:
Females must have a negative pregnancy test at the Screening Visit and Study Day -1 (admission to Clinical Unit) and must not be lactating and must be of non-childbearing potential, confirmed at Screening by fulfilling one of the following criteria:
Have a Body Mass Index (BMI) between 18 and 30 kg/m2
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Brooklyn | Maryland | 21225 | United States |
Qualified researchers can request access to anonymized individual patient-leveldata from AstraZeneca group of companies sponsored clinical trials via therequest portal Vivli.org. All requests will be evaluated as per the AZ disclosurecommitment:https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure."Yes",indicates that AZ are accepting requests for IPD, but this does not mean allrequests will be approved.
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AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
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| Baxdrostat | Drug | Baxdrostat tablet will be administered orally. |
|
To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. |
| EE: Up to Day 21, LNG: Up to Day 23 |
| Area under concentration-time curve from time zero to infinity (AUCinf) of EE/LNG | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. | EE: Up to Day 21, LNG: Up to Day 23 |
| Time to reach maximum observed concentration (tmax) | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. | EE: Up to Day 21, LNG: Up to Day 23 |
| Terminal elimination half-life (t1/2λz) | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. | EE: Up to Day 21, LNG: Up to Day 23 |
| Terminal rate constant (λz) | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. | EE: Up to Day 21, LNG: Up to Day 23 |
| Ratio of EE or LNG to EE (alone) or LNG (alone) based on AUCinf (RAUCinf) | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. | EE: Up to Day 21, LNG: Up to Day 23 |
| Ratio of EE or LNG to EE (alone) or LNG (alone) based on AUClast (RAUClast) | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. | EE: Up to Day 21; LNG: Up to Day 23 |
| Ratio of EE or LN to EE (alone) or LNG (alone) based on Cmax (RCmax) | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. | EE: Up to Day 21; LNG: Up to Day 23 |
| Number of participants with adverse event (AEs) | To examine the safety and tolerability of baxdrostat alone and in combination with combined oral EE and LNG. | From screening (Day -28 to Day -2) to 8.5 weeks |
| Maximum observed drug concentration (Cmax) of Baxdrostat | To assess the PK of baxdrostat in healthy female participants of non-childbearing potential. | Baxdrostat: Day 18 to Day 22 |
| Observed lowest concentration before the next dose is administered (Day 22 pre-dose) (Ctrough) | To assess the PK of baxdrostat in healthy female participants of non-childbearing potential. | Baxdrostat: Day 18 to Day 22 |