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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
190
100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks
Matching PF-04191834 placebo tablets to be administered BID for two weeks
Matching naproxen placebo tablets to be administered BID for 4 weeks
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.
Time frame: Baseline (Day 1 of Visit 3) and end of treatment Period 1 (Day 15+1 of Visit 5)
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.
Time frame: Baseline (Day 28 of Visit 7) and end of treatment Period 2 (Day 43+1 of Visit 9)
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.
Time frame: 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
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.
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Matching PF-04191834 placebo tablets to be administered BID for two weeks
100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks
Matching naproxen placebo tablets to be administered BID for 4 weeks
100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks
Naproxen 500 mg tablet administered BID for a total of four weeks
Matching PF-04191834 placebo tablets to be administered BID for two weeks
Naproxen 500 mg tablet administered BID for a total of four weeks
Matching PF-04191834 placebo tablets to be administered BID for two weeks
100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks
Pfizer Investigational Site
Peoria, Arizona, United States
Pfizer Investigational Site
Phoenix, Arizona, United States
Pfizer Investigational Site
Phoenix, Arizona, United States
Pfizer Investigational Site
Anaheim, California, United States
Pfizer Investigational Site
Carmichael, California, United States
Pfizer Investigational Site
Fair Oaks, California, United States
Pfizer Investigational Site
San Diego, California, United States
Pfizer Investigational Site
Denver, Colorado, United States
Pfizer Investigational Site
DeLand, Florida, United States
Pfizer Investigational Site
Pensacola, Florida, United States
...and 21 more locations
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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).
Time frame: 4 days prior to baseline visits (Visits 3 for Period 1 and Vist 8 for Period 2) up to 7 days after baseline visits
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).
Time frame: 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
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.
Time frame: Day -7 (Visit 2) up to 28-day follow-up (Visit 10)
Plasma Concentration of PF-04191834
Time frame: Pre-dose and post-dose (1 to 3 hours) on Days 1, 8, 15, 29, 36, and 43
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.
Time frame: Day -7 (Visit 2) up to Day 43 (Visit 9 or End of Treatment Period 2)