Clinical Study to Investigate Effect of Macitentan on Riociguat Pharmacokinetics

NCT03389321 | Completed Phase 1

• 2 other identifiers: AC-055-1232017-003502-41
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Both macitentan and riociguat are indicated in the treatment of pulmonary arterial hypertension (PAH) and may be administered concomitantly. The primary objective of this study is to evaluate the effect of macitentan administered for 11 days on the pharmacokinetics (PK) (i.e., amount and time of presence in the blood of riociguat) of a single dose of riociguat in healthy male subjects.

Conditions

Healthy Subjects

Keywords

pharmacokinetics; macitentan; riociguat

Outcome Measures

Primary Outcomes (2)

• Area under the plasma concentration-time curve (AUC) from zero to infinity [AUC(0-inf)] of riociguat

  AUC(0-inf) of riociguat will be assessed following administration of riociguat alone or concomitantly with macitentan.

  Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)

• Maximum plasma concentration (Cmax) of riociguat

  The maximum observed plasma concentration of riociguat will be assessed following administration of riociguat alone or concomitantly with macitentan.

  Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)

Secondary Outcomes (6)

• Time to reach Cmax (tmax) of riociguat and its metabolite M1

  Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)

• Elimination half life (t1/2) of riociguat and its metabolite M1

  Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)

• AUC(0-t) of riociguat and its metabolite M1

  Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)

• AUC(0-inf) of riociguat metabolite M1

  Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)

• Maximum plasma concentration (Cmax) of riociguat metabolite M1

  Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)

Study Arms (1)

Treatment A-B

EXPERIMENTAL

All subjects will receive treatment A followed by treatment B. Treatment A consists of a single oral dose (1 mg) of riociguat (Adempas) on Day 1. Treatment B consists of a loading oral dose of 30 mg macitentan (Opsumit) (3 tablets of 10 mg) on Day 5, then 10 mg of macitentan once daily from Day 6 to Day 15, with a concomitant administration of riociguat (1 mg) on Day 10.

Drug: Riociguat (Adempas); Drug: Macitentan (Opsumit)

Interventions

Riociguat (Adempas) DRUG

Riociguat film-coated tablets for oral administration at a strength of 1 mg

Treatment A-B

Macitentan (Opsumit) DRUG

Macitentan film-coated tablets for oral administration at a strength of 10 mg

Also known as: ACT-064992

Treatment A-B

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male subjects aged between 18 and 45 years (inclusive) at screening who signed informed consent prior to any study-mandated procedure;
• Healthy on the basis of physical examination, cardiac evaluations (12-lead ECG) and laboratory tests performed at screening;
• Body mass index of 18 to 30 Kg/m2 (inclusive) at screening;
• Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 50-90 beats per minute (inclusive).

You may not qualify if:

• Known allergic reactions or hypersensitivity to macitentan, riociguat, any drug of the same classes, or any of their excipients;
• Any contraindication for riociguat treatment;
• Known hypersensitivity or allergy to natural rubber latex;
• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions;
• 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 treatments;
• 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;
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

CRS Clinical Research Services Mannheim

Mannheim, 68167, Germany

Location

MeSH Terms

Interventions

riociguat; macitentan

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 the subjects included in the study will be included in a single group and will receive the drugs according to the same sequence

Study Record Dates

• First Submitted: December 27, 2017
• First Posted: January 3, 2018
• Study Start: January 9, 2018
• Primary Completion: February 6, 2018
• Study Completion: February 6, 2018
• Last Updated: February 8, 2018

Record last verified: 2018-02

Locations

DE (1)