Clinical Study to Investigate Effect of Macitentan on Riociguat Pharmacokinetics

Healthy Subjects Clinical Trial

Official title:

A Single-center, Open-label, One-sequence, Two-treatment Study to Investigate the Effect of Macitentan at Steady State on the Pharmacokinetics of Riociguat in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03389321
• Other study ID #: AC-055-123
• Secondary ID: 2017-003502-41
• Status: Completed
• Phase: Phase 1
• First received: December 27, 2017
• Last updated: February 7, 2018
• Start date: January 9, 2018
• Est. completion date: February 6, 2018

Study information

• Verified date: February 2018
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 6, 2018
• Est. primary completion date: February 6, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Key Inclusion Criteria:

• 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).

Key Exclusion Criteria:

• 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.

Other protocol defined inclusion and exclusion criteria may apply.

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Riociguat (Adempas)
Riociguat film-coated tablets for oral administration at a strength of 1 mg
• Macitentan (Opsumit)
Macitentan film-coated tablets for oral administration at a strength of 10 mg

Locations

Country	Name	City	State
Germany	CRS Clinical Research Services Mannheim	Mannheim

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Time to reach Cmax (tmax) of riociguat and its metabolite M1	The maximum observed time to reach Cmax of riociguat and M1 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	Elimination half life (t1/2) of riociguat and its metabolite M1	t1/2 of riociguat and M1 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	AUC(0-t) of riociguat and its metabolite M1	AUC(0-t) is the area under the plasma concentration-time curve from zero to time t of the last measured concentration above the limit of quantification. It will be determined for both riociguat and its metabolite M1 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	AUC(0-inf) of riociguat metabolite M1	AUC(0-inf) of M1 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	Maximum plasma concentration (Cmax) of riociguat metabolite M1	The maximum observed plasma concentration of M1 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	Trough concentration (Ctrough) of macitentan and its metabolite ACT-132577	Ctrough of macitentan and its metabolite ACT-132577 will be assessed during the treatment period with macitentan (Day 10 to Day 15)	Day 10 to Day 15 (before macitentan administration) and in the morning of Day 16