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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Healthy Participants

Treatments: Drug: Baxdrostat; Drug: EE/LNG

Study type: Interventional

Funder types: Industry

Identifiers

NCT06657105

D6970C00006

Details and patient eligibility

About

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.

Full 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.

Enrollment: 22 patients

Sex: Female

Ages: 35 to 75 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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22 participants in 3 patient groups

Period 1: Ethinyl estradiol/Levonorgestrel (EE/LNG)

Experimental group

Description:

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).

Treatment:

Drug: EE/LNG

Period 2: Baxdrostat

Experimental group

Description:

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

Treatment:

Drug: Baxdrostat

Period 3: Baxdrostat + EE/LNG

Experimental group

Description:

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).

Treatment:

Drug: EE/LNG

Drug: Baxdrostat