Clinical trial NCT06657105: 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
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Baxdrostat
Aldosterone
Ethinyl estradiol/ Levonorgestrel
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-10-24
Enrollment: 22
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Area under concentration-time curve from time zero to infinity (AUCinf)
timeFrame: EE: Up to Day 21, LNG: Up to Day 23
measure: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: EE: Up to Day 21, LNG: Up to Day 23
measure: Maximum observed drug concentration (Cmax)
timeFrame: EE: Up to Day 21, LNG: Up to Day 23
Secondary outcomes:
measure: Maximum observed drug concentration (Cmax) of EE/LNG
timeFrame: EE: Up to Day 21, LNG: Up to Day 23
measure: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of EE/LNG
timeFrame: EE: Up to Day 21, LNG: Up to Day 23
measure: Area under concentration-time curve from time zero to infinity (AUCinf) of EE/LNG
timeFrame: EE: Up to Day 21, LNG: Up to Day 23
measure: Time to reach maximum observed concentration (tmax)
timeFrame: EE: Up to Day 21, LNG: Up to Day 23
measure: Terminal elimination half-life (t1/2λz)
timeFrame: EE: Up to Day 21, LNG: Up to Day 23
measure: Terminal rate constant (λz)
timeFrame: EE: Up to Day 21, LNG: Up to Day 23
measure: Ratio of EE or LNG to EE (alone) or LNG (alone) based on AUCinf (RAUCinf)
timeFrame: EE: Up to Day 21, LNG: Up to Day 23
measure: Ratio of EE or LNG to EE (alone) or LNG (alone) based on AUClast (RAUClast)
timeFrame: EE: Up to Day 21; LNG: Up to Day 23
measure: Ratio of EE or LN to EE (alone) or LNG (alone) based on Cmax (RCmax)
timeFrame: EE: Up to Day 21; LNG: Up to Day 23
measure: Number of participants with adverse event (AEs)
timeFrame: From screening (Day -28 to Day -2) to 8.5 weeks
measure: Maximum observed drug concentration (Cmax) of Baxdrostat
timeFrame: Baxdrostat: Day 18 to Day 22
measure: Observed lowest concentration before the next dose is administered (Day 22 pre-dose) (Ctrough)
timeFrame: Baxdrostat: Day 18 to Day 22
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: Research Site
state: Maryland
Study officials:
References: