Healthy SubjectsPhase 1NCT03389321
Clinical Study to Investigate Effect of Macitentan on Riociguat Pharmacokinetics
A Phase 1 study testing Riociguat (Adempas) and Macitentan (Opsumit) in people with Healthy Subjects, run by Actelion at 1 site in Germany.
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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects
- What is being tested?
- Riociguat (Adempas) and Macitentan (Opsumit)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- 9 Jan 2018to 6 Feb 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- Riociguat (Adempas), Macitentan (Opsumit)
- Keywords
- pharmacokinetics, macitentan, riociguat
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Riociguat (Adempas)Drug
Riociguat film-coated tablets for oral administration at a strength of 1 mg
Macitentan (Opsumit)Drug
Also called ACT-064992
Macitentan film-coated tablets for oral administration at a strength of 10 mg
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Riociguat (Adempas); Drug: Macitentan (Opsumit) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
The maximum observed time to reach Cmax of riociguat and M1 will be assessed following administration of riociguat alone or concomitantly with macitentan.
Measured: 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
t1/2 of riociguat and M1 will be assessed following administration of riociguat alone or concomitantly with macitentan.
Measured: 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
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.
Measured: 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
AUC(0-inf) of M1 will be assessed following administration of riociguat alone or concomitantly with macitentan.
Measured: 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
The maximum observed plasma concentration of M1 will be assessed following administration of riociguat alone or concomitantly with macitentan.
Measured: 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
Ctrough of macitentan and its metabolite ACT-132577 will be assessed during the treatment period with macitentan (Day 10 to Day 15)
Measured: Day 10 to Day 15 (before macitentan administration) and in the morning of Day 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2018
- Study start9 Jan 2018
- Primary completion6 Feb 2018
- Study completion6 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy SubjectsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All the subjects included in the study will be included in a single group and will receive the drugs according to the same sequence
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shirin Bruderer, PhD, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03389321
- Sponsor's protocol ID
- AC-055-123
- Other IDs
- 2017-003502-41, 2017
- Status last verified
- Feb 2018
- First submitted
- 27 Dec 2017
- Last updated
- 8 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03389321
- Acronym / sponsor ID
- AC-055-123
- Conditions
- Healthy Subjects
- Keywords
- pharmacokinetics, macitentan, riociguat
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- 9 Jan 2018 (actual)
- Primary completion
- 6 Feb 2018 (actual)
- Study completion
- 6 Feb 2018 (actual)
- First posted
- 3 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All the subjects included in the study will be included in a single group and will receive the drugs according to the same sequence
| Arm | Type | Receives |
|---|---|---|
| Treatment A-B | Experimental | Drug: Riociguat (Adempas), Drug: Macitentan (Opsumit)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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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 (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Riociguat (Adempas)Riociguat film-coated tablets for oral administration at a strength of 1 mg | Drug | Treatment A-B |
| Macitentan (Opsumit)Also: ACT-064992Macitentan film-coated tablets for oral administration at a strength of 10 mg | Drug | Treatment A-B |
Primary outcome
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.
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.
6 secondary outcomes
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)
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)
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-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)
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)
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shirin Bruderer, PhD study director
Actelion
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Riociguat (Adempas) and Macitentan (Opsumit) in people with Healthy Subjects, run by Actelion at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2018.