Clinical Study to Investigate Effect of Macitentan on Riociguat Pharmacokinetics

February 7, 2018 updated by: Actelion

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Mannheim, Germany, 68167
        • CRS Clinical Research Services Mannheim

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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)
Riociguat film-coated tablets for oral administration at a strength of 1 mg
Drug: Macitentan (Opsumit)
Macitentan film-coated tablets for oral administration at a strength of 10 mg
Other Names:
  • ACT-064992

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Area under the plasma concentration-time curve (AUC) from zero to infinity [AUC(0-inf)] of riociguat
Time Frame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
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
Time Frame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to reach Cmax (tmax) of riociguat and its metabolite M1
Time Frame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
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)
Elimination half life (t1/2) of riociguat and its metabolite M1
Time Frame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
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)
AUC(0-t) of riociguat and its metabolite M1
Time Frame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
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)
AUC(0-inf) of riociguat metabolite M1
Time Frame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
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)
Maximum plasma concentration (Cmax) of riociguat metabolite M1
Time Frame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
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)
Trough concentration (Ctrough) of macitentan and its metabolite ACT-132577
Time Frame: Day 10 to Day 15 (before macitentan administration) and in the morning of Day 16
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Actelion

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 9, 2018

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 6, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 6, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 27, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 27, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 3, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 8, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 7, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AC-055-123
  • 2017-003502-41 (EUDRACT_NUMBER)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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