Clinical Study to Investigate the Effect of Macitentan on the Concentrations of Rosuvastatin in the Blood of Healthy Male Subjects

NCT ID: NCT03359291

Last Updated: 2025-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-03
• Study Completion Date: 2017-12-04

Brief Summary

The aim of this Phase 1 trial is to study a potential drug-drug interaction between macitentan and rosuvastatin, a model substrate of various transporter proteins (e.g. in the gut).

Detailed Description

Rosuvastatin is a substrate of various transporter proteins including breast cancer resistance protein (BCRP) and organic anion-transporting polypeptides (OATP). It is unknown to which extent macitentan has an effect, if any, on BCRP transporters, especially intestinal BCRP. The primary purpose of this Phase 1 study is to investigate the effect of macitentan on the pharmacokinetics of rosuvastatin, a model BCRP substrate.

Conditions

Healthy Subjects

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Sequence AB

Subjects participate in two study periods: During the first period (treatment A), they receive a single oral dose of rosuvastatin on Day 1. During the second period (treatment B), they receive a single oral loading dose of macitentan on Day 5 and oral doses of macitentan from Day 6 to Day 16 (i.e., 11 doses). Subjects receive a single oral dose of 10 mg rosuvastatin concomitantly with macitentan in the morning of Day 10.

Group Type: EXPERIMENTAL

Rosuvastatin

Intervention Type: DRUG

Single oral dose of 10 mg rosuvastatin (film-coated tablet) on Day 1 and Day 10

Macitentan

Intervention Type: DRUG

Single oral dose of 30 mg macitentan (film-coated tablet) on Day 5 and 10 mg macitentan administered orally from Day 6 to Day 16

Interventions

Rosuvastatin

Single oral dose of 10 mg rosuvastatin (film-coated tablet) on Day 1 and Day 10

Intervention Type: DRUG

Macitentan

Single oral dose of 30 mg macitentan (film-coated tablet) on Day 5 and 10 mg macitentan administered orally from Day 6 to Day 16

Intervention Type: DRUG

Other Intervention Names

ACT-064992

Eligibility Criteria

Inclusion Criteria

• Signed informed consent in the local language prior to any study-mandated procedure.
• Healthy male subjects aged between 18 and 55 years (inclusive) at screening.
• No clinically significant findings on the physical examination at screening.
• Body mass index of 18.0 to 30.0 kg/m2 (inclusive) at screening.
• Systolic blood pressure 100-140 mmHg, diastolic blood pressure 60-90 mmHg, and pulse rate 50-90 beats per minute (inclusive), measured on the dominant arm, after 5 min in the supine position at screening.
• 12-lead electrocardiogram (ECG) without clinically relevant abnormalities, measured after 5 min in the supine position at screening.
• Hematology and clinical chemistry test results not deviating from the normal range to a clinically relevant extent at screening.
• Negative results from urine drug screen and alcohol breath test at screening and Day -1.
• Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.

Exclusion Criteria

• Known allergic reactions or hypersensitivity to macitentan, rosuvastatin, any drug of the same classes, or any of their excipients.
• Any contraindication for rosuvastatin treatment.
• History or clinical evidence of myopathy.
• Subjects of Asian race.
• Known hypersensitivity or allergy to natural rubber latex.
• Values of hepatic aminotransferase (alanine aminotransferase and aspartate aminotransferase) outside of the normal range at screening.
• Hemoglobin or hematocrit outside of the normal range at screening.
• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study treatment(s) (appendectomy and herniotomy allowed, cholecystectomy not allowed).
• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
• Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture).
• Previous exposure to macitentan.
• Previous exposure to rosuvastatin.
• Treatment with another investigational drug within 3 months prior to screening or participation in more than 3 investigational drug studies within 1 year prior to screening.
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
• Excessive caffeine consumption, defined as ≥ 800 mg per day at screening.
• Nicotine intake (e.g., smoking, nicotine patch, nicotine chewing gum or electronic cigarettes) within 3 months prior to screening and inability to refrain from nicotine intake from screening until End-Of-Study (EOS).
• Previous treatment with any prescribed medications (including vaccines) or over-the-counter (OTC) medications (including herbal medicines such as St John's Wort, homeopathic preparations, vitamins, and minerals) within 3 weeks prior to first study treatment administration.
• Loss of 250 mL or more of blood within 3 months prior to screening.
• Positive results from the hepatitis serology, except for vaccinated subjects or subjects with past but resolved hepatitis, at screening.
• Positive results from the HIV serology at screening.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
• Legal incapacity or limited legal capacity at screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shirin Bruderer, PhD

Role: STUDY_DIRECTOR

Actelion

Locations

CRS Clinical Research Services Mannheim

Mannheim, , Germany

Countries

Germany

Other Identifiers

AC-055-122

Identifier Type: -

Identifier Source: org_study_id