The investigators propose that once daily administration of PF-00489791, a phosphodiesterase inhibitor, will reduce vasospasm and improve symptoms and signs associated with Primary and Secondary Raynaud's Phenomenon.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
243
Subjects with Secondary Raynaud's Phenomenon will receive PF-00489791 4 mg once a day for the first 4 week cross over period and then placebo once a day for the second 4 week cross over period
Subjects with Secondary Raynaud's Phenomenon will receive placebo once a day for the first 4 week cross over period and then PF-00489791 4 mg once a day for the second 4 week cross over period
Subjects with Secondary Raynaud's Phenomenon will receive PF-00489791 20 mg once a day for the first 4 week cross over period and then placebo once a day for the second 4 week cross over period
Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4
The Raynaud's Condition score (RCS) is participant's rating of difficulty considering number of attacks, duration, amount of pain, numbness, or other symptoms caused in the fingers (including painful sores) due to the Raynaud's phenomenon every day and impact of Raynaud's alone on use of hands every day. An 11 point Likert scale is used to rate the difficulty caused by the condition each day with 0 = no difficulty and 10 = extreme difficulty. Participants were asked to select the number that best describes their difficulty, with higher score indicating worse condition. Average daily score was considered for participants completing more than 1 Raynaud's pain score scale on a day. Baseline value was calculated as mean of the scores over 7 days prior to treatment start. Week 4 value was calculated as mean of the scores over the 7-day period prior to Week 4.
Time frame: Baseline, Week 4
Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4
Change from baseline in the number of Raynaud's attacks at Week 1, Week 2, Week 3 and Week 4 was calculated from the number of attacks reported over the 7-day period prior to each week from the patient diary, respectively.
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4
Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4
Mean duration of Raynaud's attacks for a time period was calculated as sum of recorded durations of attacks in the time period divided by total number of attacks in the time period where duration was recorded.
Time frame: Baseline, Week 4
Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4
Participants were asked to rate their worst Raynaud's pain in the past 24 hours using an 11 point Likert scale, with 0 = no Raynaud's pain and 10 = the worst possible pain. Highest (most severe) response was considered for participants responding at more than 1 point on the scale. Average daily score was considered for participants completing more than 1 Raynaud's pain score scale on a day. Baseline value was calculated as mean of the scores over 7 days prior to treatment start. Post-baseline value was calculated as mean of the scores over the 7-day period prior to the visit.
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Subjects with Secondary Raynaud's Phenomenon will receive placebo once a day for the first 4 week cross over period and then PF-00489791 20 mg once a day for the second 4 week cross over period
Subjects with Primary Raynaud's Phenomenon will receive PF-00489791 4 mg once a day for the first 4 week cross over period and then placebo once a day for the second 4 week cross over period
Subjects with Primary Raynaud's Phenomenon will receive placebo once a day for the first 4 week cross over period and then PF-00489791 4 mg once a day for the second 4 week cross over period
Subjects with Primary Raynaud's Phenomenon will receive PF-00489791 20 mg once a day for the first 4 week cross over period and then placebo once a day for the second 4 week cross over period
Subjects with Primary Raynaud's Phenomenon will receive placebo once a day for the first 4 week cross over period and then PF-00489791 20 mg once a day for the second 4 week cross over period
Stanford Hospital and Outpatient Center
Redwood City, California, United States
University of Connecticut Health Center
Farmington, Connecticut, United States
Georgetown University Hospital
Washington D.C., District of Columbia, United States
Arthritis and Rheumatology of Georgia
Atlanta, Georgia, United States
Rockford Orthopedic Associates
Rockford, Illinois, United States
Diagnostic Rheumatology and Research, PC
Indianapolis, Indiana, United States
Memorial Health System, Inc. dba Memorial Medical Group Clinical Research Institute
South Bend, Indiana, United States
Johns Hopkins University - Division of Rheumatology
Baltimore, Maryland, United States
The Center for Rheumatology and Bone Research
Wheaton, Maryland, United States
Clinical Pharmacology Study Group
Worcester, Massachusetts, United States
...and 45 more locations
Time frame: Baseline, Week 1, 2, 3, 4
Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort
Presence of ulcer was assessed at baseline. At post-baseline visits, each ulcer was measured and scored: 1= smaller or improved compared to previous visit, 2= same as previous visit, 3= bigger or worse than previous visit, and 4= new. If a new digital ulcer develops during the course of the study, the measurement and scoring were initiated on this additional ulcer. Healed ulcers were not counted into the number of ulcers. Participants with SRP in the per-protocol population with at least 1 digital ulcer present at any assessment were evaluable for this measure. Results are reported for participants with presence of ulcer at baseline and decrease from baseline in ulcers at post-baseline visits.
Time frame: Baseline, Day 14, 28
Plasma Concentration of PF-00489791 and Its Metabolites
Only participants receiving PF-00489791 were to be analyzed for this outcome. Data have been calculated by setting plasma concentration values below the lower limit of quantification to 0. The lower limit of quantification is 0.0100 microgram per milliliter (mcg/mL). Data for plasma concentration of PF-00489791 metabolites was not analyzed, as it was not intended to be a secondary endpoint and was deemed optional.
Time frame: Day 1, 15, 29 (Day 1, 15, 29 for first intervention period), 43, 57, 71 (Day 1, 15, 29 for second intervention period)
Number of Participants With Laboratory Test Abnormalities
Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (less than \[\<\] 0.8\*lower limit of normal\[LLN\]); leukocytes (\<0.6 LLN /greater than \[\>\] 1.5\*upper LN \[ULN\]; platelets (\<0.5\*LLN/\>1.75\*ULN); neutrophils, lymphocytes (\<0.8\* LLN/\>1.2\*ULN); eosinophils, basophils, monocytes (\>1.2\*ULN); bilirubin (\>1.5\*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma GT, alkaline phosphatase (\>3\*ULN); BUN, creatinine (\>1.3\*ULN); glucose (\<0.6 LLN/\>1.5\*ULN); uric acid (\>1.2\*ULN); sodium (\<0.95\*LLN/\>1.05\*ULN); potassium, calcium, chloride, bicarbonate (\<0.9\*LLN/\>1.1\*ULN); albumin, total protein (\<0.8\*LLN/\>1.2\*ULN); creatine kinase (\>2.0\*ULN); Urine Specific Gravity, Urine pH, urine blood, urine glucose, urine protein, urine ketones, urine leukocytes esterase (\>=1 high-powered field). Total number of participants with any laboratory abnormalities was reported.
Time frame: Screening up to 28 days after last study dose (up to 98 days)
Number of Participants With Clinically Significant Changes in Vital Signs and Orthostatic Blood Pressure Measurements
Vital signs assessment included measurement of supine and standing pulse rate, systolic and diastolic blood pressures. Criteria for clinically significant vital signs and orthostatic blood pressure measurements were based on investigator's judgement.
Time frame: Screening up to 28 days after last study dose (up to 98 days)
Number of Participants With Abnormal Electrocardiogram (ECG) Values
ECG assessment included measurement of PR, QRS, QT,corrected QT interval (QTc)values. Criteria for clinically significant ECG values were based on investigator's judgement.
Time frame: Screening up to 28 days after last study dose (up to 98 days)