A Study Of The Safety And Efficacy Of PF-04191834 In Patients With Osteoarthritis Of The Knee

Osteoarthritis, Knee Clinical Trial

Official title:

A Phase 2 Randomized, Double-Blinded, Double-Dummy, Placebo And Active Controlled Two Cohort Two-Way Cross-Over, Multi-Centre Clinical Trial To Examine The Pain Relief Produced By 2 Weeks Of Daily Oral Administration Of A 5-Lipoxygenase (5-Lox) Inhibitor PF-04191834 Alone And In Combination With Naproxen In Patients With Flare-Enriched Osteoarthritis Of The Knee

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01147458
• Other study ID #: B0041007
• Status: Terminated
• Phase: Phase 2
• First received: June 16, 2010
• Last updated: May 30, 2013
• Start date: July 2010
• Est. completion date: February 2011

Study information

• Verified date: May 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

PF-04191834 works in animal models by inhibiting one of the enzymes, 5-lipoxygenasein which is involved in the pathway that causes inflammation and pain. The purpose of this study is to test how effective, safe and tolerated PF-04191834 is in patients with osteoarthritis of the knee by itself or with naproxen, particularly to test if patients have less pain.

Description:

This study has been terminated in response to a reported serious adverse event (SAE). The sponsor's assessment of the limited data available at the time of the initial SAE report was that the SAE may alter the potential benefit - risk profile of the study medication.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 190
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Subjects must have a diagnosis of osteoarthritis based on the American College of Rheumatology criteria confirmed by an X-ray

• Subjects must be willing and able to stop all current pain therapy for the duration of the study

• Subjects must be willing and able to complete a daily diary

Exclusion Criteria:

• BMI of >39 kg/m2

• Known allergy or hypersensitivity to naproxen

• Any condition or medical history that might interfere with the subject's ability to complete the study visits and assessments

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• PF-04191834
100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks
• PF-04191834 placebo
Matching PF-04191834 placebo tablets to be administered BID for two weeks
• Naproxen placebo
Matching naproxen placebo tablets to be administered BID for 4 weeks
• PF-04191834 placebo
Matching PF-04191834 placebo tablets to be administered BID for two weeks
• PF-04191834
100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks
• Naproxen placebo
Matching naproxen placebo tablets to be administered BID for 4 weeks
• PF-04191834
100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks
• Naproxen
Naproxen 500 mg tablet administered BID for a total of four weeks
• PF-04191834 placebo
Matching PF-04191834 placebo tablets to be administered BID for two weeks
• Naproxen
Naproxen 500 mg tablet administered BID for a total of four weeks
• PF-04191834 placebo
Matching PF-04191834 placebo tablets to be administered BID for two weeks
• PF-04191834
100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks

Locations

Country	Name	City	State
Canada	Pfizer Investigational Site	Quebec
Canada	Pfizer Investigational Site	Quebec
Canada	Pfizer Investigational Site	Sherbrooke	Quebec
Canada	Pfizer Investigational Site	St. John's	Newfoundland and Labrador
Sweden	Pfizer Investigational Site	Goteborg
Sweden	Pfizer Investigational Site	Stockholm
United States	Pfizer Investigational Site	Anaheim	California
United States	Pfizer Investigational Site	Arlington	Virginia
United States	Pfizer Investigational Site	Austin	Texas
United States	Pfizer Investigational Site	Carmichael	California
United States	Pfizer Investigational Site	Columbus	Ohio
United States	Pfizer Investigational Site	DeLand	Florida
United States	Pfizer Investigational Site	Denver	Colorado
United States	Pfizer Investigational Site	Edina	Minnesota
United States	Pfizer Investigational Site	Fair Oaks	California
United States	Pfizer Investigational Site	Fargo	North Dakota
United States	Pfizer Investigational Site	Las Vegas	Nevada
United States	Pfizer Investigational Site	Monroe	North Carolina
United States	Pfizer Investigational Site	Oklahoma City	Oklahoma
United States	Pfizer Investigational Site	Overland Park	Kansas
United States	Pfizer Investigational Site	Overland Park	Kansas
United States	Pfizer Investigational Site	Pensacola	Florida
United States	Pfizer Investigational Site	Peoria	Arizona
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Phoenix	Arizona
United States	Pfizer Investigational Site	Phoenix	Arizona
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	South Bend	Indiana
United States	Pfizer Investigational Site	South Miami	Florida
United States	Pfizer Investigational Site	St. Paul	Minnesota
United States	Pfizer Investigational Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Western Ontario & McMaster (WOMAC) Osteoarthritis Index Pain Score at the End of Treatment Period 1	The WOMAC Pain subscale, comprised of 5 questions regarding the amount of pain experienced in the index joint, was calculated as the mean of the scores from the 5 individual questions. The WOMAC Pain subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-20, with higher scores indicating higher pain.	Baseline (Day 1 of Visit 3) and end of treatment Period 1 (Day 15+1 of Visit 5)	No
Primary	Change From Baseline in Western Ontario & McMaster (WOMAC) Osteoarthritis Index Pain Score at the End of Treatment Period 2	The WOMAC Pain subscale, comprised of 5 questions regarding the amount of pain experienced in the index joint, was calculated as the mean of the scores from the 5 individual questions. The WOMAC Pain subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-20, with higher scores indicating higher pain.	Baseline (Day 28 of Visit 7) and end of treatment Period 2 (Day 43+1 of Visit 9)	No
Secondary	WOMAC Stiffness Domain Score	The WOMAC Stiffness subscale, comprised of 2 questions regarding the amount of stiffness experienced in the index joint, was calculated as the mean of the scores from the 2 individual questions. The WOMAC Stiffness subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-8, with higher scores indicating more stiffness.	Baseline (Day 1 of Visit 3 for Period 1 and Day 28 of Visit 7 for Period 2), Day 15+1 of Visit 5 for Period 1, and Day 43+1 of Visit 9 for Period 2	No
Secondary	WOMAC Physical Function Domain Score	The WOMAC Physical Function subscale refers to the participant's ability to move around and perform usual activities of daily living. The WOMAC Physical Function subscale, comprised of 17 questions regarding the degree of difficulty experienced in the index joint, was calculated as the mean of the scores from the 17 individual questions. The WOMAC Physical Function subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-68, with higher scores indicating worse function.	Baseline (Day 1 of Visit 3 for Period 1 and Day 28 of Visit 7 for Period 2), Day 15+1 of Visit 5 for Period 1, and Day 43+1 of Visit 9 for Period 2	No
Secondary	WOMAC Total Score	The WOMAC total score was calculated as the sum of Pain subscale score (5 questions), Stiffness subscale score (2 questions) and Physical Function subscale score (17 questions), with a total of 24 questions(score range:0=none, 4=extreme) giving a possible total score range from 0 to 96 . lower subscale scores represent less pain, less stiffness, or better physical performance.	Baseline (Day 1 of Visit 3 for Period 1 and Day 28 of Visit 7 for Period 2), Day 15+1 of Visit 5 for Period 1, and Day 43+1 of Visit 9 for Period 2	No
Secondary	Importance Weighted Total WOMAC Score	Importance weighted total WOMAC score was calculated using all subscales including Pain, Stiffness and Physical Function subscales (24 questions in total,score range: 0=none to 4= extreme,giving a possible overall score range of 0-96).Lower subscale scores represent less pain, less stiffness, or better physical performance.	Baseline (Day 1 of Visit 3 for Period 1 and Day 28 of Visit 7 for Period 2), Day 15+1 of Visit 5 for Period 1, and Day 43+1 of Visit 9 for Period 2	No
Secondary	Daily Diary Pain Score During Week 1 of Each Treatment Period	The daily diary pain was assessed using an 11-point numerical rating scale (NRS) ranging from 0 to 10 (0 = no pain; 10 = the worst pain possible).	4 days prior to baseline visits (Visits 3 for Period 1 and Vist 8 for Period 2) up to 7 days after baseline visits	No
Secondary	Daily Diary Pain Score During Week 2 of Each Treatment Period	The daily diary pain was assessed using an 11-point numerical rating scale (NRS) ranging from 0 to 10 (0 = no pain; 10 = the worst pain possible).	Over the last 4 days before baseline visits (Visits 3 for Period 1 and Visit 8 for Period 2) and over the last 6 days before Visit 5 for Period 1 and Visit 9 for Period 2	No
Secondary	Rescue Medication Use	Rescue medication use was collected daily in a daily diary, in which participants noted the amount of rescue medication (number of pills) taken each day. Participants were provided with rescue medication paracetamol/acetaminophen throughout the study including the Washout Period and the Initial Pain Assessment Period. Paracetamol/acetaminophen was taken as needed to a maximum of 2000 mg per day, but must be discontinued 48 hours prior to the Baseline visit (Visit 3). From Visit 3 onwards, participants might take up to 2000 mg of paracetamol/acetaminophen per day up to 3 days per week.	Day -7 (Visit 2) up to 28-day follow-up (Visit 10)	No
Secondary	Plasma Concentration of PF-04191834		Pre-dose and post-dose (1 to 3 hours) on Days 1, 8, 15, 29, 36, and 43	No
Secondary	Urinary Leukotriene E4 (LTE4) Levels	LTE4 is a terminal metabolic product of arachidonic acid by 5-LO. Its synthesis is dependent upon the activity of 5-LO and it is eliminated through urinary clearance. Hence, the level of urinary LTE4 (uLTE4) excretion may be an indicator of endogenous 5-LO activity.	Day -7 (Visit 2) up to Day 43 (Visit 9 or End of Treatment Period 2)	No

External Links

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