E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary arterial hypertension |
|
E.1.1.1 | Medical condition in easily understood language |
Pulmonary Arterial Hypertension is an increase in blood pressure in the pulmonary arteries leading to shortness of breath, dizziness, fainting and other symptoms. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Pulmonary arterial hypertension |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to assess whether temporary switching from a stable oral dose of selexipag to an intravenous (i.v.) dose of selexipag providing comparable exposure to active metabolite ACT-333679 and switching back to the initial oral dose of selexipag is safe and well tolerated in subjects with stable pulmonary arterial hypertension (PAH). |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent prior to any study-mandated procedure. 2. Male and female subjects at least 18 to 75 years inclusive. 3. Subjects with PAH belonging to the Updated Clinical Classification Group 1 4. Subjects who have been prescribed Uptravi® in compliance with local prescribing information (i.e., SmPC or USPI). 5. Stable PAH defined as WHO Functional Class (FC) I-III at Visit 1 and Visit 2 and no change (i.e., introduction or dose change) in PAH-specific medication (i.e., ERA, PDE-5 inhibitor or sGC stimulator) and diuretics in the last 28 days prior to Visit 2. 6. Subjects currently treated with Uptravi® at a stable dose (i.e. unchanged dose) for at least 28 days before Visit 2. 7. A woman of childbearing potential is eligible only if she has a negative urine pregnancy test at Visit 1 and at Visit 2. |
|
E.4 | Principal exclusion criteria |
1. Pregnant, planning to become pregnant or lactating. 2. Known and documented moderate or severe hepatic impairment. 3. Subjects having received gemfibrozil at any time since initiation of Uptravi®. 4. Treatment with any prostacyclin and prostacyclin analogs within 28 days prior to Visit 1. 5. SBP < 90 mmHg at Visit 1 or at Visit 2. 6. Known or suspected uncontrolled hyperthyroidism. 7. Severe renal failure and ongoing or planned dialysis. 8. Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease. This includes subjects for whom participation in the study might be associated with excessive stress, in the opinion of the investigator. 9. Known concomitant life-threatening disease with a life expectancy < 12 months. 10. Treatment with another investigational treatment within 3 months of Visit 1. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Main safety variables are: - Proportion of discontinuations due to prostacyclin-associated adverse events (AEs) - Proportion of AEs and serious AEs - Proportion of prostacyclin-associated AEs - Proportion of AEs related to injection site reactions - Proportion of PAH-related AEs |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Over Period 1, Period 2 and Period 3 combined |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Single-sequence 3-period crossover design |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |