A Drug-drug Interaction Trial in Healthy Female Participants to Investigate the Effect of Aprocitentan on Combined Hormonal Contraceptives

NCT06799884 | Completed Phase 1

• 2 other identifiers: ID-080-1112024-517224-19-00
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug Drug Interaction

Outcome Measures

Primary Outcomes (6)

• Maximum plasma concentration (Cmax) of ethinyl estradiol/levonorgestrel

  The measured individual plasma concentrations will be used to directly obtain Cmax.

  TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)

• Time to maximum plasma concentration (tmax) of ethinyl estradiol/levonorgestrel

  The measured individual plasma concentrations will be used to directly obtain tmax.

  TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)

• Area under the Plasma Concentration-Time Curve (AUC 0-t) of ethinyl estradiol/levonorgestrel

  Change to AUC 0-t will be derived by non compartmental analysis of the concentration-time profiles.

  TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)

• Area under the Plasma Concentration-Time Curve (AUC 0-infinity) of ethinyl estradiol/levonorgestrel

  Change to AUC 0-infinity will be derived by non compartmental analysis of the concentration-time profiles.

  TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)

• Terminal half-life (t1/2) of ethinyl estradiol/levonorgestrel

  t1/2 will be derived by non compartmental analysis of the concentration-time profiles.

  TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)

• Trough plasma concentration (Ctrough) of aprocitentan

  Ctrough will be based on measured individual plasma concentrations of aprocitentan.

  Prior to administration on Day 10, 11, 12 and 13 in TP B2

Study Arms (3)

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.

Drug: Ethinyl Estradiol / Levonorgestrel Oral Tablet

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.

Drug: Aprocitentan

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.

Drug: Ethinyl Estradiol / Levonorgestrel Oral Tablet; Drug: Aprocitentan

Interventions

Ethinyl Estradiol / Levonorgestrel Oral Tablet DRUG

Coated tablet of 20 µg ethinyl estradiol and 100 µg levonorgestrel

Also known as: LOETTE

Aprocitentan and ethinyl estradiol/levonorgestrel (LOETTE); Ethinyl estradiol/levonorgestrel (LOETTE)

Aprocitentan DRUG

Film-coated tablet of aprocitentan 25 mg

Aprocitentan; Aprocitentan and ethinyl estradiol/levonorgestrel (LOETTE)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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®

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

CEPHA s.r.o.

Pilsen, 323 00, Czechia

Location

MeSH Terms

Interventions

Ethinyl Estradiol-Norgestrel Combination; aprocitentan

Intervention Hierarchy (Ancestors)

Ethinyl Estradiol; Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Norgestrel; Norpregnenes; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Clinical Trials

  Idorsia Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: January 29, 2025
• Study Start: January 18, 2025
• Primary Completion: February 21, 2025
• Study Completion: February 21, 2025
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)