Healthy SubjectsPhase 1NCT04281342
To Study the Effect of Aprocitentan on the Electrical Activity of the Heart in Healthy Men and Women
A Phase 1 study testing Aprocitentan 25 mg and Aprocitentan 100 mg in people with Healthy Subjects, run by Idorsia Pharmaceuticals Ltd. at 1 site in Germany.
Trial summary
To demonstrate that multiple-dose administration of oral therapeutic and supratherapeutic doses of aprocitentan do not have a clinically relevant effect on the QT interval. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects
- What is being tested?
- Aprocitentan 25 mg and Aprocitentan 100 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteGermany
- Study dates
- 14 Jan 2020to 3 Sep 2021
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Signed informed consent in a language understandable to the subject prior to any study-mandated procedure.
- Ability to communicate well with the investigator, in a language understandable to the subject, and to understand and comply with the requirements of the study.
- No clinically significant findings on the physical examination at screening.
- Body mass index 18.0 to 30.0 kg/m2 (inclusive) at screening.
- Systolic blood pressure 90-140 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 50-90 bpm (all inclusive), measured on the same arm, after 5 minutes in the supine position at screening.
- 12-lead safety ECG: QTcF less than 450 ms for male subjects and less than 470 ms for female subjects, QRS less than 110 ms, PR less than 220 ms, and resting HR greater than 50 bpm and less than 90 bpm with no clinically relevant abnormalities on 12-lead ECG after at least 5 min in the supine position at Screening and on Day 1 pre-dose of Period 1.
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- No clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry) at screening.
- Negative results from urine drug screen, urine cotinine test, and breath alcohol tests at screening and on Day -1 of each period.
- A woman of childbearing potential (WoCBP) is eligible only if the following applies:
- Negative serum pregnancy test at screening.
- Negative urine pregnancy test on Day -1 of each period.
- Agreement to consistently and correctly use a highly effective method of contraception from screening up to at least 30 days after last study treatment administration in the last period with in-between periods included.
- Women of non-childbearing potential (WoNCBP) must meet at least one of the following criteria:
- Previous bilateral salpingectomy, salpingo-oophorectomy or hysterectomy,
- Confirmed premature ovarian failure,
- Post-menopausal.
Who cannot join
- Pregnant or lactating women.
- Previous exposure to aprocitentan or macitentan.
- Known hypersensitivity to aprocitentan or macitentan or any of the drug product excipients, or treatments of the same class.
- Any contraindication or known hypersensitivity to moxifloxacin or any of the drug product excipients or to other fluoroquinolone antibiotics.
- Known hypersensitivity or allergy to natural rubber latex.
- History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment (appendectomy and herniotomy allowed, cholecystectomy not allowed).
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- Acute, ongoing, recurrent, or chronic systemic disease able to interfere with the evaluation of the study.
- 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 2 weeks or 5 t½ (whichever is longer) prior to first study treatment administration with the exception of contraceptives in female subjects.
- History or presence of rhythm disorders (e.g., sinoatrial heart block, sick-sinus syndrome, second- or third-degree atrioventricular block, long QT syndrome, symptomatic bradycardia, atrial flutter, or atrial fibrillation) or hypokalemia.
- Legal incapacity or limited legal capacity at screening.
Trial locations and contacts
1 site in 1 country.
Germany1 site
CRS Clinical Research Services Mannheim GmbH
Mannheim, Baden-Wurttemberg, 68167
About this study
Official title: Prospective, Single-center, Randomized, Double-blind, Placebo- and Moxifloxacin-controlled, 4-way Crossover Phase 1 Study to Assess the Effect of Multiple Therapeutic and Supratherapeutic Doses of Aprocitentan on the QT Interval Duration in Healthy Subjects
To demonstrate that multiple-dose administration of oral therapeutic and supratherapeutic doses of aprocitentan do not have a clinically relevant effect on the QT interval.
- Conditions
- Healthy Subjects
- Being tested
- Aprocitentan 25 mg, Aprocitentan 100 mg, Matching placebo, Moxifloxacin control to establish assay sensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aprocitentan 25 mgDrug
Also called ACT-132577
Repeated administration of a 25 mg oral dose of aprocitentan, once daily from Day 1 to Day 10, followed by 18 days of observation.
Aprocitentan 100 mgDrug
Also called ACT-132577
Repeated administration of a 100 mg oral dose of aprocitentan, once daily from Day 1 to Day 10, followed by 18 days of observation.
Matching placeboDrug
Repeated administration of an oral dose of aprocitentan-matching placebo, once daily from Day 1 to Day 10, followed by 18 days of observation.
Moxifloxacin control to establish assay sensitivityOther
Repeated administration of an oral dose of aprocitentan-matching placebo, once daily from Day 1 to Day 9. On Day 10, oral administration of one single 400 mg moxifloxacin tablet open-label, followed by 18 days of observation.
| Study group | Role | What they receive |
|---|---|---|
| Aprocitentan 25 mg | Experimental | Therapeutic dose level Receives: Drug: Aprocitentan 25 mg |
| Aprocitentan 100 mg | Experimental | Supratherapeutic dose level Receives: Drug: Aprocitentan 100 mg |
| Matching placebo | Placebo comparator | Not described Receives: Drug: Matching placebo |
| Moxifloxacin | Other | Not described Receives: Other: Moxifloxacin control to establish assay sensitivity |
What is being measured
The primary outcome is the main question the study is designed to answer.
Placebo-corrected change from baseline in QT interval corrected with Fridericia's formula (ΔΔQTcF)
Measured: Multiple predefined time points related to study treatment administration on Day 1 and Day 10 to 11 of each treatment.
Secondary outcomes (6)
Aprocitentan trough plasma concentrations (Ctrough)
Measured: Day 2 to Day 9
Aprocitentan plasma Cmax, first dose
Measured: Pre-defined times on the first dosing day (Day 1) up to 15 hours after last dose
Aprocitentan plasma Cmax, steady state
Measured: Pre-defined times on the last dosing day (Day 10) up to 15 hours after last dose
Area under the plasma concentration-time curve (AUCτ) during a dosage interval (τ) of aprocitentan
Measured: Day 1 to Day 10
Aprocitentan attainment of steady-state conditions
Measured: Day 1 to Day 10
Accumulation index between the first and the last dosing day of aprocitentan
Measured: Day 1; Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2020
- Study start14 Jan 2020
- Primary completion3 Aug 2021
- Study completion3 Sep 2021
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
- Randomised
- Intervention model
- Crossover
- Model description
- Each subject will be randomized immediately prior to first study treatment administration on Day 1 Period 1 to one of 12 treatment sequences following a 3 × 4 × 4 Williams square design. Moxifloxacin will be open-label on Day 10 in one period.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Idorsia Pharmaceuticals Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04281342
- Sponsor's protocol ID
- ID-080-108
- Other IDs
- 2019-003617-34, 2019
- Status last verified
- Nov 2022
- First submitted
- 20 Feb 2020
- Last updated
- 23 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Single-center, Randomized, Double-blind, Placebo- and Moxifloxacin-controlled, 4-way Crossover Phase 1 Study to Assess the Effect of Multiple Therapeutic and Supratherapeutic Doses of Aprocitentan on the QT Interval Duration in Healthy Subjects
- ClinicalTrials.gov ID
- NCT04281342
- Acronym / sponsor ID
- ID-080-108
- Conditions
- Healthy Subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- 14 Jan 2020 (actual)
- Primary completion
- 3 Aug 2021 (actual)
- Study completion
- 3 Sep 2021 (actual)
- First posted
- 24 Feb 2020 (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.
To demonstrate that multiple-dose administration of oral therapeutic and supratherapeutic doses of aprocitentan do not have a clinically relevant effect on the QT interval.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Each subject will be randomized immediately prior to first study treatment administration on Day 1 Period 1 to one of 12 treatment sequences following a 3 × 4 × 4 Williams square design. Moxifloxacin will be open-label on Day 10 in one period.
| Arm | Type | Receives |
|---|---|---|
| Aprocitentan 25 mg | Experimental | Drug: Aprocitentan 25 mgTherapeutic dose level |
| Aprocitentan 100 mg | Experimental | Drug: Aprocitentan 100 mgSupratherapeutic dose level |
| Matching placebo | Placebo comparator | Drug: Matching placebo |
| Moxifloxacin | Other | Other: Moxifloxacin control to establish assay sensitivity |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- Signed informed consent in a language understandable to the subject prior to any study-mandated procedure.
- Ability to communicate well with the investigator, in a language understandable to the subject, and to understand and comply with the requirements of the study.
- No clinically significant findings on the physical examination at screening.
- Body mass index 18.0 to 30.0 kg/m2 (inclusive) at screening.
- Systolic blood pressure 90-140 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 50-90 bpm (all inclusive), measured on the same arm, after 5 minutes in the supine position at screening.
Key exclusion criteria (10 listed)
- Pregnant or lactating women.
- Previous exposure to aprocitentan or macitentan.
- Known hypersensitivity to aprocitentan or macitentan or any of the drug product excipients, or treatments of the same class.
- Any contraindication or known hypersensitivity to moxifloxacin or any of the drug product excipients or to other fluoroquinolone antibiotics.
- Known hypersensitivity or allergy to natural rubber latex.
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 |
|---|---|---|
| Aprocitentan 25 mgAlso: ACT-132577Repeated administration of a 25 mg oral dose of aprocitentan, once daily from Day 1 to Day 10, followed by 18 days of observation. | Drug | Aprocitentan 25 mg |
| Aprocitentan 100 mgAlso: ACT-132577Repeated administration of a 100 mg oral dose of aprocitentan, once daily from Day 1 to Day 10, followed by 18 days of observation. | Drug | Aprocitentan 100 mg |
| Matching placeboRepeated administration of an oral dose of aprocitentan-matching placebo, once daily from Day 1 to Day 10, followed by 18 days of observation. | Drug | Matching placebo |
| Moxifloxacin control to establish assay sensitivityRepeated administration of an oral dose of aprocitentan-matching placebo, once daily from Day 1 to Day 9. On Day 10, oral administration of one single 400 mg moxifloxacin tablet open-label, followed by 18 days of observation. | Other | Moxifloxacin |
Primary outcome
Placebo-corrected change from baseline in QT interval corrected with Fridericia's formula (ΔΔQTcF)
Time frame: Multiple predefined time points related to study treatment administration on Day 1 and Day 10 to 11 of each treatment.
6 secondary outcomes
Aprocitentan trough plasma concentrations (Ctrough)
Time frame: Day 2 to Day 9
Aprocitentan plasma Cmax, first dose
Time frame: Pre-defined times on the first dosing day (Day 1) up to 15 hours after last dose
Aprocitentan plasma Cmax, steady state
Time frame: Pre-defined times on the last dosing day (Day 10) up to 15 hours after last dose
Area under the plasma concentration-time curve (AUCτ) during a dosage interval (τ) of aprocitentan
Time frame: Day 1 to Day 10
Aprocitentan attainment of steady-state conditions
Time frame: Day 1 to Day 10
Accumulation index between the first and the last dosing day of aprocitentan
Time frame: Day 1; Day 10
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 23 Nov 2022.
- Individual participant dataSharing planned: No
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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.
Clinical Trials study director
Idorsia Pharmaceuticals Ltd.
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 Aprocitentan 25 mg and Aprocitentan 100 mg in people with Healthy Subjects, run by Idorsia Pharmaceuticals Ltd. 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 16 inclusion and 10 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 23 Nov 2022. 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. Some participants in this study may receive a placebo. 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?
Placebo-corrected change from baseline in QT interval corrected with Fridericia's formula (ΔΔQTcF) (time frame: Multiple predefined time points related to study treatment administration on Day 1 and Day 10 to 11 of each treatment.). 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 23 Nov 2022.