E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Vasospasm in Primary and Secondary Raynaud’s Phenomenon |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037912 |
E.1.2 | Term | Raynaud's phenomenon |
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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 this study is to evaluate the efficacy of different doses of PF-00489791 on the Raynaud’s Condition Score (RCS) in PRP and SRP patients. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of different doses of PF-00489791 on the frequency of RP attacks in PRP and SRP subjects;
• To evaluate the efficacy of different doses of PF-00489791 on the total duration of RP attacks in PRP and SRP subjects;
• To evaluate the efficacy of different doses of PF-00489791 on the Raynaud’s pain Score in PRP and SRP subjects;
• To evaluate the efficacy of different doses of PF-00489791 on the ulcer counts and score in SRP patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study.
1. Male or female subjects between 18 and 65 years of age.
2. Active Raynaud's Phenomenon defined as episodic digital pallor followed by cyanosis and/or erythema in response to cold or emotion.
3. SRP subjects must also have a diagnosis of scleroderma defined by the American College of Rheumatology (ACR) criteria or by the presence of at least 3 of the 5 features of the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias).
4. Subjects must have at least seven RP attacks per week on five or more days per week. This may be self-reported at the Screen Visit.
5. Stable disease and medication requirements over the previous 2 months. Calcium channel blockers and NSAIDs are permitted, but subjects will not be able to change the dose or begin calcium channel blockers/NSAIDs upon enrollment in the study. ACE-I are permitted if required for hypertension and/or scleroderma related renal disease.
6. Unchanged immunosuppressive therapy 3 months before treatment with PF-00489791.
7. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
8. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. |
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E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the study: 1. Subjects who currently smoke. Ex-smokers are defined as having not smoked for at least 3 months. 2. Subjects using smoking cessation treatments (eg nicotine patches). 3. Subjects with a history of stroke, myocardial infarction or life threatening arrhythmia within the last six months. 4. Subjects with uncontrolled hypertension.(SBP>150 mm Hg, DBP >100 mmHg). 5. Subjects with uncontrolled diabetes mellitus with HbA1c>7%. 6. Subjects who had severe cardiac failure (New York Heart Association IV classification) or unstable angina within the last six months. 7. Subjects with hemodynamic instability or systolic arterial pressure less than 90 mmHg and/or symptomatic orthostatic hypotension. 8. Subjects with impairment of hepatic function (ALT and/or AST >3 x Upper Limits of Normal (ULN) and/or bilirubin ≥2 mg/dL) at screening. 9. Subjects with impairment of renal function (serum creatinine >2.5 x ULN) at screening. 10. Subjects who have had surgical sympathectomy performed in the previous 12 months. 11. Subjects with a history of upper extremity deep vein thrombosis or lymphedema within the previous 3 months. 12. Subjects with known hereditary degenerative retinal disorders (such as retinitis pigmentosa) or history of non-arteritic anterior ischemic optic neuropathy (NAION) or untreated proliferative diabetic retinopathy. 13. Subjects with previous intolerance or allergy to PDE5 inhibitors or a history of multiple clinically significant allergies. 14. Subjects who currently use phosphodiesterase inhibitors or with previous chronic use of phosphodiesterase inhibitors for any reason (eg, sildenafil, tadalafil, vardenafil). • Theophylline; pentoxifylline • Aspirin (except 81 mg per day or low-dose per local regulations); 15. Subjects who are unable to withdraw from vasodilators or any of the following therapies for 14 days before commencement of study: • Potent cytochrome P450 3A4 inhibitors eg, itraconazole, erythromycin, ketoconazole, protease inhibitors; • Nitrates or nitric oxide donors; • Ritonavir or Nicorandil; • Theophylline; • Alpha blockers; • Iloprost; • Bosentan; • NSAIDS; • ACE-I or angiotensin receptor inhibitor; • Corticosteroids (unless on a stable dose of less than or equal to 10 mg of prednisone a day or equivalent for at least 3 months); • Aspirin (except 81 mg per day); • Dipyridamole; • Other antiplatelet agents (eg Ticlopidine, Clopidogrel). 16. Subjects with active alcoholism and/or drug abuse within the past 5 years. 17. Subjects with a history of HIV, Hepatitis B or C infection. 18. Subjects who are pregnant or breast feeding or considering pregnancy in next 4 months. Females of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined in this protocol from at least 14 days prior to the first dose of study medication and through 14 days following the last dose of study drug. 19. Subjects with prior participation in a clinical trial for an investigational drug and/or agent within 30 days of entry. 20. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the RCS during the fourth week of treatment from baseline, comparing active drug to placebo. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
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.8.3 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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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 | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |