A Single-center, Open-label, Fixed-sequence Trial to Investigate the Effect of Multiple-dose Aprocitentan on the Single-dose Pharmacokinetics of Combined Oral Contraceptives in Healthy Female Participants

Idorsia Pharmaceuticals Ltd.1 个研究点分布在 1 个国家目标入组 19 人开始时间: 2025年1月18日最近更新: 2025年3月11日

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Idorsia Pharmaceuticals Ltd.
入组人数: 19
试验地点: 1
主要终点: Maximum plasma concentration (Cmax) of ethinyl estradiol/levonorgestrel

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The goal of this clinical trial is to learn if drug aprocitentan has an effect on hormonal contraceptives in healthy female volunteers. The main question it aims to answer is:

Does aprocitentan modify the fate of hormonal contraceptives in the body?

Trial participants will:

Take a single dose of hormonal contraceptives (fixed combination) alone
Take aprocitentan every day for 2 weeks
Take a single dose of the same hormonal contraceptives at the same time as the 10th administration of aprocitentan.

详细描述

The main objective of the trial is to evaluate the influence of aprocitentan at steady-state on the single-dose pharmacokinetics (PK) of combined oral contraceptives.

19 healthy female participants will be enrolled to have at least 16 evaluable participants.

Following a screening period (from full signature of the informed consent form [ICF] to enrollment; 10 to 28 days prior to first trial intervention administration), eligible participants (meeting all inclusion criteria and none of the exclusion criteria) will be enrolled in the trial to participate in two sequential trial periods, Trial Period A and Trial Period B, with an in-between period of at least 7 days. Trial Period B will be split into two sequential sub-periods, Trial Period B1 and Trial Period B2.

Trial Period A: Starts with a single administration of trial intervention on Day 1 and ends with an End-of-Trial Period (EoTP) assessment on Day 5. Trial intervention administration on Day 1 will be followed by a 96-hour observation period for safety monitoring and PK sampling.
Trial Period B1: Trial intervention will be administered from Day 1 to Day 9, with assessments for PK sampling and safety monitoring performed throughout.
Trial Period B2: Starts with administration of trial intervention on Day 10 and ends with an EoTP assessment on Day 14. Trial intervention will be administered from Day 10 to Day 13, with assessments for PK sampling and safety monitoring performed throughout.

Trial participation of an individual participant ends with the completion of the Participant Last Visit, which will be performed 10-14 days after the last administration of trial intervention. A post-trial safety follow up is performed 30-40 days after last administration of trial intervention.

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: 18 Years 至 65 Years（Adult, Older Adult）
性别: Female
接受健康志愿者: 是

入选标准

•Signed and dated informed consent form (ICF) prior to any trial-mandated procedure.
•Healthy female participants aged from 18 to 65 years at the time of signing the ICF.
•Ability to communicate well with the investigator, in a language understandable to the participant, and to understand and comply with the trial requirements.
•Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) at Screening.
•Normal or not clinically significant abnormal systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 45-90 bpm (inclusive), measured on either arm, after 5 min in the supine position at Screening and on Day 1 (predose) of Trial Period A (TP A).
•Participant of childbearing potential who has a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1 (predose) of TP A.
•Participant of childbearing potential who agrees to use two reliable methods of non- hormonal contraception from Screening and for at least 30 days after the last trial intervention administration, or be sexually inactive, or have a vasectomized partner.
•Participant of non-childbearing potential, i.e., postmenopausal (defined as 12 consecutive months with no menses without an alternative medical cause, confirmed by an follicle stimulating hormone test), with previous bilateral salpingectomy, bilateral salpingo-oophorectomy, or hysterectomy, or with premature ovarian failure (confirmed by a specialist), XY genotype, Turner syndrome, uterine agenesis).

排除标准

•Known hypersensitivity to aprocitentan, ethinylestradiol, or levonorgestrel, or treatments of the same class, or any of their excipients.
•Clinically relevant findings on the physical examination at Screening.
•Clinically relevant abnormalities on 12-lead electrocardiogram (ECG), measured after 5 min in a supine position at Screening or on Day 1 (pre-dose) of TP A.
•Clinically relevant findings in clinical laboratory tests (hematology and clinical chemistry) at Screening.
•History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the trial interventions (appendectomy and herniotomy allowed if performed > 12 weeks prior to first trial intervention administration, cholecystectomy not allowed).
•Acute, ongoing, recurrent, or chronic systemic disease able to interfere with the evaluation of the trial results.
•Previous clinically relevant history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
•Previous therapy with hormonal contraceptives or hormone replacement therapy within 2 months prior to first trial intervention administration.
•Pregnant, planning to become pregnant during the trial, or lactating participant of childbearing potential.
•Participant presenting any contraindications for LOETTE®

研究组 & 干预措施

Ethinyl estradiol/levonorgestrel (LOETTE)

Experimental

In Trial Period A, participants will receive a single oral dose of 20µg ethinyl estradiol/100 µg levonorgestrel in the morning of Day 1.

干预措施: Ethinyl Estradiol / Levonorgestrel Oral Tablet (Drug)

Aprocitentan

Experimental

In Trial Period B1, participants will receive a once daily oral dose of 25 mg aprocitentan in the morning of Day 1 to Day 9.

干预措施: Aprocitentan (Drug)

Aprocitentan and ethinyl estradiol/levonorgestrel (LOETTE)

Experimental

In Trial Period B2, participants will receive a once daily oral dose of 25 mg aprocitentan in the morning of Day 10 to Day 13.

On Day 10, participants will receive a single oral dose of 20µg ethinyl estradiol/100 µg levonorgestrel, administered concomitantly to aprocitentan.

干预措施: Ethinyl Estradiol / Levonorgestrel Oral Tablet (Drug)

Aprocitentan and ethinyl estradiol/levonorgestrel (LOETTE)

Experimental

In Trial Period B2, participants will receive a once daily oral dose of 25 mg aprocitentan in the morning of Day 10 to Day 13.

On Day 10, participants will receive a single oral dose of 20µg ethinyl estradiol/100 µg levonorgestrel, administered concomitantly to aprocitentan.

干预措施: Aprocitentan (Drug)