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.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Area under concentration-time curve from time zero to infinity (AUCinf)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
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).
干预措施: EE/LNG (Drug)
Period 2: Baxdrostat
Participants will self-administer the baxdrostat tablet once a day from Day 6 to Day 16.
干预措施: Baxdrostat (Drug)
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).
干预措施: EE/LNG (Drug)
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).
干预措施: Baxdrostat (Drug)
结局指标
主要结局
Area under concentration-time curve from time zero to infinity (AUCinf)
时间窗: 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)
时间窗: 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)
时间窗: 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.
次要结局
- 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)
- Terminal rate constant (λz)(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)(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)(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)(EE: Up to Day 21; LNG: Up to Day 23)
- Number of participants with adverse event (AEs)(From screening (Day -28 to Day -2) to 8.5 weeks)
- Maximum observed drug concentration (Cmax) of Baxdrostat(Baxdrostat: Day 18 to Day 22)
- Observed lowest concentration before the next dose is administered (Day 22 pre-dose) (Ctrough)(Baxdrostat: Day 18 to Day 22)