PF-00489791 For The Treatment Of Raynaud's

Phase 2

Completed

Conditions: Raynaud's Disease
Peripheral Vascular Disease

Interventions: Drug: PF-00489791

Registration Number: NCT01090492

Lead Sponsor: Pfizer

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 243

Inclusion Criteria

Active Raynaud's Phenomenon
Stable disease and medication requirements over the previous two months
For Secondary Raynaud's Phenomenon subjects, a diagnosis of scleroderma using the American College of Rheumatology criteria or by the presence of at least 3/5 features of CREST syndrome
both sexes

Exclusion Criteria

Uncontrolled hypertension, diabetes mellitus, angina, or using oral nitrates
Smoking within 3 months or smoking cessation using nicotine products
Subjects currently taking sildenafil, tadalafil or vardenafil
Subjects with ulnar arterial occlusive disease as shown by a modified Allen test
Pregnant or breast feeding or considering pregnancy in next 4 months
Participation in trial for investigational drug within 30 days

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Secondary Raynaud 4 mg dose (period 1)	PF-00489791	-
Secondary Raynaud 20 mg dose (period 2)	PF-00489791	-
Secondary Raynaud 20 mg dose (period 1)	PF-00489791	-
Secondary Raynaud 4 mg dose (period 2)	PF-00489791	-
Primary Raynaud 4 mg dose (period 1)	PF-00489791	-
Primary Raynaud 20 mg dose (period 1)	PF-00489791	-
Primary Raynaud 4 mg dose (period 2)	PF-00489791	-
Primary Raynaud 20 mg dose (period 2)	PF-00489791	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4	Baseline, 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4	Baseline, 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.
Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4	Baseline, Week 1, Week 2, Week 3, Week 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.
Plasma Concentration of PF-00489791 and Its Metabolites	Day 1, 15, 29 (Day 1, 15, 29 for first intervention period), 43, 57, 71 (Day 1, 15, 29 for second intervention period)	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.
Number of Participants With Abnormal Electrocardiogram (ECG) Values	Screening up to 28 days after last study dose (up to 98 days)	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.
Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4	Baseline, Week 1, 2, 3, 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.
Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort	Baseline, Day 14, 28	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.
Number of Participants With Clinically Significant Changes in Vital Signs and Orthostatic Blood Pressure Measurements	Screening up to 28 days after last study dose (up to 98 days)	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.
Number of Participants With Laboratory Test Abnormalities	Screening up to 28 days after last study dose (up to 98 days)	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.

Trial Locations

Locations (55): Stanford Hospital and Outpatient Center
🇺🇸
Redwood City, California, United States
Diagnostic Rheumatology and Research, PC
🇺🇸
Indianapolis, Indiana, United States
Arthritis and Rheumatology of Georgia
🇺🇸
Atlanta, Georgia, United States
Medicity S.A.S
🇨🇴
Bucaramanga, Colombia
Idearg Sas
🇨🇴
Bogotá, Cundinamarca, Colombia
AAIR Research Center
🇺🇸
Rochester, New York, United States
Altoona Center for Clinical Research
🇺🇸
Duncansville, Pennsylvania, United States
Semmelweis Egyetem, Ersebeszeti Klinika
🇭🇺
Budapest, Hungary
Bacs-Kiskun Megyei Onkormanyzat Korhaza Szegedi Tudomanyegyetem AOK Oktato Korhaza
🇭🇺
Kecskemet, Hungary
Unidad de Investigacion en Enfermedades Cronico Degenerativas
🇲🇽
Guadalajara, Jalisco, Mexico
Prywatna Praktyka Lekarska Prof. UM Dr hab. med. Pawel Hrycaj
🇵🇱
Poznan, Poland
Hospital Angeles. Centro Medico del Potosi
🇲🇽
San Luis Potosi, Mexico
Hospital Del Mar
🇪🇸
Barcelona, Spain
Slaskie Centrum Osteoporozy
🇵🇱
Katowice, Poland
Prywatna Praktyka Lekarska Dr Med. Pawel Hrycaj
🇵🇱
Poznan, Poland
Georgetown University Hospital
🇺🇸
Washington, District of Columbia, United States
Rockford Orthopedic Associates
🇺🇸
Rockford, Illinois, United States
Memorial Health System, Inc. dba Memorial Medical Group Clinical Research Institute
🇺🇸
South Bend, Indiana, United States
Clinical Pharmacology Study Group
🇺🇸
Worcester, Massachusetts, United States
Johns Hopkins University - Division of Rheumatology
🇺🇸
Baltimore, Maryland, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Physician Research Collaboration, LLC
🇺🇸
Lincoln, Nebraska, United States
West Michigan Rheumatology, PLLC
🇺🇸
Grand Rapids, Michigan, United States
Regional Rheumatology Associates
🇺🇸
Binghamton, New York, United States
Rheumatic Disease Associates, Ltd.
🇺🇸
Willow Grove, Pennsylvania, United States
Rainier Clinical Research Center, Inc.
🇺🇸
Renton, Washington, United States
Rheumatology Research Associates
🇨🇦
Ottawa, Ontario, Canada
CTC, Centrum för klinisk provning, Sahlgrenska Universitetssjukhuset
🇸🇪
Goteborg, Sweden
Sir Mortimer B. Davis, Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada
Centro Integral de Reumatologia e Inmunologia CIREI
🇨🇴
Bogota, Cundinamarca, Colombia
Fundacion Instituto de Reumatologia Fernando Chalem
🇨🇴
Bogota, Cundinamarca, Colombia
Fakultni nemocnice Hradec Kralove
🇨🇿
Hradec Kralove, Czechia
REVMATOLOGIE s.r.o.,
🇨🇿
Brno, Czechia
Revmatologicky ustav
🇨🇿
Praha 2, Czechia
Dermatologisches Ambulatorium Hamburg-Alstertal
🇩🇪
Hamburg, Germany
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
🇲🇽
Mexico, DF, Mexico
Katedra i Klinika Dermatologii, Wenerologii i Alergologii Akademii Medycznej we Wroclawiu
🇵🇱
Wroclaw, Poland
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Reumatologkliniken Skanes Universitetssjukhus Lund
🇸🇪
Lund, Sweden
Karolinska Universitetssjukhuset Solna, Reumatologiska kliniken
🇸🇪
Stockholm, Sweden
The Center for Rheumatology and Bone Research
🇺🇸
Wheaton, Maryland, United States
The Center for Rheumatology
🇺🇸
Albany, New York, United States
Arthritis Centre Health Sciences Centre
🇨🇦
Winnipeg, Manitoba, Canada
UMDNJ - Robert Wood Johnson Medical Center Clinical Research Center
🇺🇸
New Brunswick, New Jersey, United States
University of Connecticut Health Center
🇺🇸
Farmington, Connecticut, United States
The Catholic University of Korea, Seoul St. Mary's Hospital/ Rheumatology, Internal Medicine
🇰🇷
Seoul, Korea, Republic of
University of Michigan Health System
🇺🇸
Ann Arbor, Michigan, United States
East Penn Rheumatology Associates, PC
🇺🇸
Bethlehem, Pennsylvania, United States
Metroplex Clinical Research Center
🇺🇸
Dallas, Texas, United States
St. Joseph's Health Centre
🇨🇦
London, Ontario, Canada
Seoul National University Hospital, Rheumatology, Internal Medicine
🇰🇷
Seoul, Korea, Republic of
Servimed E.U
🇨🇴
Bucaramanga, Santander, Colombia
Vas Megyei Markusovszky Korhaz Nonprofit Zrt, Angiologiai Szakambulancia
🇭🇺
Szombathely, Hungary
Yonsei University College of Medicine, Severance Hospital, Rheumatology, Internal Medicine
🇰🇷
Seoul, Korea, Republic of
Hospital Clinico Universitario Santiago de Compostela
🇪🇸
Santiago de Compostela, A Coruña, Spain