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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-003617-34 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aprocitentan 25 mg | Experimental | Therapeutic dose level |
|
| Aprocitentan 100 mg | Experimental | Supratherapeutic dose level |
|
| Matching placebo | Placebo Comparator |
| |
| Moxifloxacin | Other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aprocitentan 25 mg | Drug | Repeated administration of a 25 mg oral dose of aprocitentan, once daily from Day 1 to Day 10, followed by 18 days of observation. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Placebo-corrected change from baseline in QT interval corrected with Fridericia's formula (ΔΔQTcF) | Multiple predefined time points related to study treatment administration on Day 1 and Day 10 to 11 of each treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Aprocitentan trough plasma concentrations (Ctrough) | Day 2 to Day 9 | |
| Aprocitentan plasma Cmax, first dose | Pre-defined times on the first dosing day (Day 1) up to 15 hours after last dose | |
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Inclusion Criteria:
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.
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:
Women of non-childbearing potential (WoNCBP) must meet at least one of the following criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Idorsia Pharmaceuticals Ltd. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CRS Clinical Research Services Mannheim GmbH | Mannheim | Baden-Wurttemberg | 68167 | Germany |
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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.
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Placebo-controlled.
|
| Aprocitentan 100 mg | Drug | Repeated administration of a 100 mg oral dose of aprocitentan, once daily from Day 1 to Day 10, followed by 18 days of observation. |
|
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| Matching placebo | Drug | Repeated administration of an oral dose of aprocitentan-matching placebo, once daily from Day 1 to Day 10, followed by 18 days of observation. |
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| Moxifloxacin control to establish assay sensitivity | Other | 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. |
|
| Aprocitentan plasma Cmax, steady state |
| 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 | Day 1 to Day 10 |
| Aprocitentan attainment of steady-state conditions | Day 1 to Day 10 |
| Accumulation index between the first and the last dosing day of aprocitentan | Day 1; Day 10 |
| ID | Term |
|---|---|
| C572762 | aprocitentan |
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