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CompletedNCT03389321Updated Feb 8, 2018

Clinical Study to Investigate Effect of Macitentan on Riociguat Pharmacokinetics

A Phase 1 interventional study of Riociguat (Adempas) and Macitentan (Opsumit) in Healthy Subjects, sponsored by Actelion. Completed at 1 site in Germany. Open to male participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-02-08.

Sponsored by Actelion · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
20
Allocation
Not applicable
Ages
18 Years to 45 Years
Sex
Male
01

Study 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.

02

Conditions studied

  • Healthy Subjects

Keywords

  • pharmacokinetics
  • macitentan
  • riociguat
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

Eligibility criteria

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.

04

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

  • Experimental
    Treatment A-B

    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

  • DrugRiociguat (Adempas)

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

  • DrugMacitentan (Opsumit)

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

    Also known as: ACT-064992

05

What researchers measure

Primary outcomes

  1. 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.

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

  2. 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.

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

Secondary outcomes

  1. 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.

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

  2. 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.

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

  3. 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.

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

  4. AUC(0-inf) of riociguat metabolite M1

    AUC(0-inf) of M1 will be assessed following administration of riociguat alone or concomitantly with macitentan.

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

  5. 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.

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

  6. 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)

    Time frame: Day 10 to Day 15 (before macitentan administration) and in the morning of Day 16

06

Study locations

1 site
  • CRS Clinical Research Services Mannheim
    Mannheim, 68167, Germany
07

Registry details

Key details

Study ID
NCT03389321
Lead sponsor
Actelion
Responsible party
Sponsor
First posted
Jan 3, 2018
Start date
Jan 9, 2018
Primary completion
Feb 6, 2018
Completion
Feb 6, 2018
Last update
Feb 8, 2018

Study contacts

Shirin Bruderer, PhD
study director · Actelion

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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