PF-00489791 For The Treatment Of Raynaud's

Peripheral Vascular Disease Clinical Trial

Official title:

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 Phenomenon

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01090492
• Other study ID #: A7331010
• Secondary ID: EudraCT 2010-019
• Status: Completed
• Phase: Phase 2
• Start date: August 4, 2010
• Est. completion date: May 31, 2011

Study information

• Verified date: April 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 243
• Est. completion date: May 31, 2011
• Est. primary completion date: May 31, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Disease
• Peripheral Vascular Diseases
• Raynaud Disease
• Raynaud's Disease
• Vascular Diseases

Intervention

Drug:
• PF-00489791
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
• PF-00489791
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
• PF-00489791
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
• PF-00489791
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
• PF-00489791
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
• PF-00489791
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
• PF-00489791
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
• PF-00489791
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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada,  Colombia,  Czechia,  Germany,  Hungary,  Korea, Republic of,  Mexico,  Poland,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Week 4
Secondary	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.	Baseline, Week 1, Week 2, Week 3, Week 4
Secondary	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.	Baseline, Week 4
Secondary	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.	Baseline, Week 1, 2, 3, 4
Secondary	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.	Baseline, Day 14, 28
Secondary	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.	Day 1, 15, 29 (Day 1, 15, 29 for first intervention period), 43, 57, 71 (Day 1, 15, 29 for second intervention period)
Secondary	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.	Screening up to 28 days after last study dose (up to 98 days)
Secondary	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.	Screening up to 28 days after last study dose (up to 98 days)
Secondary	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.	Screening up to 28 days after last study dose (up to 98 days)

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