E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Raynaud's Phenomenon secondary to Systemic Sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
Raynaud's Phenomenon secondary to Systemic Sclerosis |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037912 |
E.1.2 | Term | Raynaud's phenomenon |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to determine the activity of selexipag on Raynaud attack frequency in subjects with Raynaud’s Phenomenon (RP) secondary to Systemic Sclerosis (SSc). |
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E.2.2 | Secondary objectives of the trial |
• to explore the effect of selexipag in reducing the impact of RP on subject's Quality of Life (QoL). • to assess the safety and tolerability of selexipag in subjects with RP secondary to SSc. • to explore relationships between plasma concentration of selexipag and its metabolite ACT-333679 to IP receptor activation or SSc biomarkers
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
At Screening visit: • Signed informed consent prior to any study-mandated procedure. • Male and female subjects aged 18 years and above with history of recurrent multiple weekly RP attacks secondary to SSc. • A woman of childbearing potential is eligible only if the following applies: −Negative urine pregnancy test at screening visit. −Agreement to undertake monthly pregnancy tests during the study and up to 30 days after study treatment discontinuation. −Agreement to use one reliable method of birth control
At randomization visit all the above apply and: • Subjects with RP who have experienced at least 7 RP attacks in the 7 days prior to the randomization visit (i.e., baseline week) with attacks on at least 5 different days.
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E.4 | Principal exclusion criteria |
At screening visit: • Known severe hepatic impairment (i.e. Child-Pugh C). • Known hypersensitivity to selexipag or drugs of the same class, or any of their excipients. • Subjects who have received prostacyclin (epoprostenol) or prostacyclin analogs (i.e., treprostenol, iloprost, beraprost) within 3 months prior to the screening visit or are scheduled to receive any of those treatments during the intended study period. • Subjects who have received a Phosphodiesterase type 5 (PDE-5) inhibitor within 1 week prior to the screening visit or are scheduled to receive any such treatment during the intended study period. • Any dose change or initiation of any of the following drugs within 1 month prior to the screening visit: oCalcium channel blockers oNitrates or nitric oxide donors oERA's oAlpha-blockers oAntithrombotic agents oNSAIDs (occasional use allowed) oAngiotensin Converting Enzyme (ACE) inhibitors oBeta-blockers oClonidine oSystemic corticosteroids oFluoxetine
At randomization visit all the above apply and: • Severe renal insufficiency: estimated creatinine clearance <30 mL/min/1.73 m² or serum creatinine >2.5 mg/dL (221 µmol/L) based on central laboratory results from screening visit blood sample • Subjects who were not compliant with run-in procedures
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the average weekly number of RP attacks during maintenance period as determined from daily entries in electronic Diaries (eDiary). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.6 | Pharmacokinetic | No |
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 |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Run-in period: single-blind placebo |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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The overall study is considered completed when all subjects have completed their 30-day safety follow-up phone call. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |