A PHASE 2A RANDOMIZED DOUBLE-BLINDED, PLACEBO AND ACTIVE CONTROLLED TWO COHORT TWO DOSES CROSS-OVER MULTI-CENTER CLINICAL STUDY TO ASSESS EFFICACY OF A ONCE DAILY ADMINISTRATION OF A PHOSPHODIESTERASE 5 INHIBITOR (PF-00489791) FOR THE TREATMENT OF VASOSPASM IN PRIMARY AND SECONDARY RAYNAUD’S PHENOMENO

• Conditions: Treatment of Vasospasm in Primary and Secondary Raynaud’s Phenomenon; MedDRA version: 12.1Level: LLTClassification code 10037912Term: Raynaud's phenomenon

• Registration Number: EUCTR2010-019009-40-DE
• Lead Sponsor: Pfizer Ltd, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-11
• Last Update Posted: 11 March 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 208

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 selfreported 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 nonarteritic 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).
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; pentoxifylline
• Alpha blockers;
• Iloprost;
• Bosentan;
• 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 or low-dose per local regulations);
• 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.;Secondary Objective: • To evaluate the efficacy of different doses of PF-00489791 on the frequency of RP attacks in PRP and SRP subjects;<br><br>• To evaluate the efficacy of different doses of PF-00489791 on the total duration of RP attacks in PRP and SRP subjects;<br><br>• To evaluate the efficacy of different doses of PF-00489791 on the Raynaud’s pain Score in PRP and SRP subjects;<br><br>• To evaluate the efficacy of different doses of PF-00489791 on the ulcer counts and score in SRP patients.;Primary end point(s): Change in the RCS during the fourth week of treatment from baseline, comparing active drug to placebo.