Healthy Participants
Conditions
Keywords
Baxdrostat, Aldosterone, Ethinyl estradiol/ Levonorgestrel
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.
Interventions
DRUGEE/LNG
EE/LNG tablet will be administered orally.
DRUGBaxdrostat
Baxdrostat tablet will be administered orally.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
35 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under concentration-time curve from time zero to infinity (AUCinf) | EE: Up to Day 21, LNG: Up to Day 23 | 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. |
| Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) | EE: Up to Day 21, LNG: Up to Day 23 | 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. |
| Maximum observed drug concentration (Cmax) | EE: Up to Day 21, LNG: Up to Day 23 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to reach maximum observed concentration (tmax) | EE: Up to Day 21, LNG: Up to Day 23 | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. |
| Terminal elimination half-life (t1/2λz) | EE: Up to Day 21, LNG: Up to Day 23 | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. |
| Terminal rate constant (λz) | EE: Up to Day 21, LNG: Up to Day 23 | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. |
| Ratio of EE or LNG to EE (alone) or LNG (alone) based on AUCinf (RAUCinf) | EE: Up to Day 21, LNG: Up to Day 23 | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. |
| Maximum observed drug concentration (Cmax) of EE/LNG | EE: Up to Day 21, LNG: Up to Day 23 | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. |
| Ratio of EE or LN to EE (alone) or LNG (alone) based on Cmax (RCmax) | EE: Up to Day 21; LNG: Up to Day 23 | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. |
| Number of participants with adverse event (AEs) | From screening (Day -28 to Day -2) to 8.5 weeks | To examine the safety and tolerability of baxdrostat alone and in combination with combined oral EE and LNG. |
| Maximum observed drug concentration (Cmax) of Baxdrostat | Baxdrostat: Day 18 to Day 22 | To assess the PK of baxdrostat in healthy female participants of non-childbearing potential. |
| Observed lowest concentration before the next dose is administered (Day 22 pre-dose) (Ctrough) | Baxdrostat: Day 18 to Day 22 | To assess the PK of baxdrostat in healthy female participants of non-childbearing potential. |
| Ratio of EE or LNG to EE (alone) or LNG (alone) based on AUClast (RAUClast) | EE: Up to Day 21; LNG: Up to Day 23 | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. |
| 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 | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. |
| Area under concentration-time curve from time zero to infinity (AUCinf) of EE/LNG | EE: Up to Day 21, LNG: Up to Day 23 | To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential. |
Countries
United States
Outcome results
None listed