A Study to Investigate the Pharmacokinetics of Ethinyl Estradiol and Levonorgestrel When Given Alone and in Combination With Baxdrostat in Healthy Females of Non-childbearing Potential

An Open-label, Fixed Sequence Study to Assess the Effect of Multiple Doses of Baxdrostat on the Pharmacokinetics of Single Doses of Combined Oral Ethinyl Estradiol and Levonorgestrel in Healthy Female Participants of Non-childbearing Potential.

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Baxdrostat; Drug: EE/LNG

Detailed Description

This is an open-label, 3-period fixed sequence study conducted at a single Clinical Unit.

The study will comprise of:

• A Screening period of maximum 28 days.
• Period 1: - From Day -1 to Day 5.
• Period 2: -From Day 6 to Day 16
• Period 3: - From Day 17 to Day 23.
• A Final Follow-up Visit, 7 (± 2) days after the last PK sample in Period 3.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Brooklyn, Maryland, United States, 21225
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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:

  1. Postmenopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range (Follicular Stimulating Hormone (FSH) > 40 mIU/mL).
  2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation or tubal occlusion.
• Have a Body Mass Index (BMI) between 18 and 30 kg/m2

Exclusion Criteria:

• History of any clinically important disease or disorder which, in the opinion of 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.
• Sex hormone therapy within one month before study.
• History of drug-related hepatic toxicity.
• History or family history of potential risk of arterial and venous thromboembolic events (eg, factor V Leiden mutation).
• History of cardiovascular risk (eg, history of myocardial infarction).
• Any laboratory values with the following deviations at the Screening Visit and Study Day -1 (admission to Clinical Unit).
• Any positive result on screening for serum HBsAg, HBcAb, HCV or HIV.
• History of any treatment with QT prolongation drugs.
• Current smokers or know history of alcohol or drug abuse.
• History or ongoing severe allergy/hypersensitivity.
• An increased risk for developing SAEs or a contraindication associated with administration of EE, or LNG such as history of thrombosis or thromboembolism, presence of estrogen dependent tumors, hypertension, migraines, and liver disease.
• Participants treated with strong CYP3A4 inhibitors or inducers within 3 months or longer (5 half-lives) prior to first administration of IMP in this study.
• Plasma donation within one month of the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months prior to the Screening Visit.
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days or 5 half-lives (whichever is longest) of the first administration of IMP in this study.
• Participants who are vegans or have medical dietary restrictions and vulnerable participants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1: Ethinyl estradiol/Levonorgestrel (EE/LNG); 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).	Drug: EE/LNG; EE/LNG tablet will be administered orally.
Experimental: Period 2: Baxdrostat; Participants will self-administer the baxdrostat tablet once a day from Day 6 to Day 16.	Drug: Baxdrostat; Baxdrostat tablet will be administered orally.
Experimental: Period 3: Baxdrostat + EE/LNG; 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).	Drug: Baxdrostat; Baxdrostat tablet will be administered orally.; Drug: EE/LNG; EE/LNG tablet will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Actual): February 3, 2025
• Study Completion (Actual): February 3, 2025

Study Registration Dates

• First Submitted: October 23, 2024
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 24, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Aldosterone; Baxdrostat; Ethinyl estradiol/ Levonorgestrel
• Other Study ID Numbers: D6970C00006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No