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

NCT03359291 | Completed Phase 1

• 1 other identifier: AC-055-122
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy Subjects

Keywords

macitentan; rosuvastatin; pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• AUC(0-inf) of rosuvastatin following administration of rosuvastatin alone (treatment A) and in combination with macitentan (treatment B)

  AUC(0-inf) is the area under the plasma concentration-time curves of rosuvastatin, calculated from time zero to the extrapolated infinite time

  From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)

• Cmax of rosuvastatin following administration of rosuvastatin alone (treatment A) and in combination with macitentan (treatment B)

  Cmax is the maximum observed plasma concentration and is directly derived from the individual plasma concentration time curves of rosuvastatin

  From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)

Secondary Outcomes (11)

• tmax of rosuvastatin following administration of rosuvastatin alone (treatment A) and in combination with macitentan (treatment B)

  From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)

• t½ of rosuvastatin following administration of rosuvastatin alone (treatment A) and in combination with macitentan (treatment B)

  From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)

• AUC(0-t) of rosuvastatin following administration of rosuvastatin alone (treatment A) and in combination with macitentan (treatment B)

  From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)

• Trough plasma concentrations of macitentan and its metabolite ACT-132577

  From Day5 to Day17

• Change from baseline in supine blood pressure

  From Day1 to end-of-study visit (Day 26-28)

Study Arms (1)

Sequence AB

EXPERIMENTAL

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.

Drug: Rosuvastatin; Drug: Macitentan

Interventions

Rosuvastatin DRUG

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

Sequence AB

Macitentan 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

Also known as: ACT-064992

Sequence AB

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

CRS Clinical Research Services Mannheim

Mannheim, 68167, Germany

Location

MeSH Terms

Interventions

Rosuvastatin Calcium; macitentan

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Shirin Bruderer, PhD

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All subjects will receive rosuvastatin alone (treatment A) or with macitentan at steady state (treatment B). A fixed sequence design was selected to avoid a lengthy washout period and unnecessary prolongation of subjects' participation in the study.

Study Record Dates

• First Submitted: November 13, 2017
• First Posted: December 2, 2017
• Study Start: November 3, 2017
• Primary Completion: December 4, 2017
• Study Completion: December 4, 2017
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)