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

NCT06657105 | Completed Phase 1 FDA Drug

• 1 other identifier: D6970C00006
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Participants

Keywords

Baxdrostat; Aldosterone; Ethinyl estradiol/ Levonorgestrel

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (12)

• Maximum observed drug concentration (Cmax) of EE/LNG

  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

  EE: Up to Day 21, LNG: Up to Day 23

• Area under concentration-time curve from time zero to infinity (AUCinf) of EE/LNG

  EE: Up to Day 21, LNG: Up to Day 23

• Time to reach maximum observed concentration (tmax)

  EE: Up to Day 21, LNG: Up to Day 23

• Terminal elimination half-life (t1/2λz)

  EE: Up to Day 21, LNG: Up to Day 23

Study Arms (3)

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).

Drug: EE/LNG

Period 2: Baxdrostat

EXPERIMENTAL

Participants will self-administer the baxdrostat tablet once a day from Day 6 to Day 16.

Drug: Baxdrostat

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).

Drug: EE/LNG; Drug: Baxdrostat

Interventions

EE/LNG DRUG

EE/LNG tablet will be administered orally.

Period 1: Ethinyl estradiol/Levonorgestrel (EE/LNG); Period 3: Baxdrostat + EE/LNG

Baxdrostat DRUG

Baxdrostat tablet will be administered orally.

Period 2: Baxdrostat; Period 3: Baxdrostat + EE/LNG

Eligibility Criteria

• Age: 35 Years - 75 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Brooklyn, Maryland, 21225, United States

Location

Study Design

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

Study Record Dates

• First Submitted: October 23, 2024
• First Posted: October 24, 2024
• Study Start: November 1, 2024
• Primary Completion: February 3, 2025
• Study Completion: February 3, 2025
• Last Updated: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

US (1)