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

• ClinicalTrials.gov Identifier: NCT01147458
• Recruitment Status: Terminated
• First Posted: June 22, 2010
• Results First Posted: May 21, 2013
• Last Update Posted: June 6, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Osteoarthritis, Knee	Drug: PF-04191834; Drug: PF-04191834 placebo; Drug: Naproxen placebo; Drug: Naproxen	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 190 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Study Start Date: July 2010
• Actual Primary Completion Date: February 2011
• Actual Study Completion Date: February 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: PF-04191834 followed by placebo; PF-04191834 600 mg BID dose followed by matched placebo plus naproxen placebo.	Drug: PF-04191834; 100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks; Drug: PF-04191834 placebo; Matching PF-04191834 placebo tablets to be administered BID for two weeks; Drug: Naproxen placebo; Matching naproxen placebo tablets to be administered BID for 4 weeks
Experimental: Placebo followed by PF-04191834; Placebo followed by 600 mg BID dose of PF-04191834 plus naproxen placebo.	Drug: PF-04191834 placebo; Matching PF-04191834 placebo tablets to be administered BID for two weeks; Drug: PF-04191834; 100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks; Drug: Naproxen placebo; Matching naproxen placebo tablets to be administered BID for 4 weeks
Experimental: PF-04191834+Naproxen followed by Naproxen; PF-04191834 600 mg BID + Naproxen 500 mg BID followed by Naproxen 500 mg BID plus PF-04191834 placebo	Drug: PF-04191834; 100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks; Drug: Naproxen; Naproxen 500 mg tablet administered BID for a total of four weeks; Drug: PF-04191834 placebo; Matching PF-04191834 placebo tablets to be administered BID for two weeks
Experimental: Naproxen followed by PF-04191834+Naproxen; Naproxen 500 mg BID followed by PF-04191834 600 mg BID + Naproxen 500 mg BID	Drug: Naproxen; Naproxen 500 mg tablet administered BID for a total of four weeks; Drug: PF-04191834 placebo; Matching PF-04191834 placebo tablets to be administered BID for two weeks; Drug: PF-04191834; 100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Western Ontario & McMaster (WOMAC) Osteoarthritis Index Pain Score at the End of Treatment Period 1 [ Time Frame: Baseline (Day 1 of Visit 3) and end of treatment Period 1 (Day 15+1 of Visit 5) ]
   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.
2. Change From Baseline in Western Ontario & McMaster (WOMAC) Osteoarthritis Index Pain Score at the End of Treatment Period 2 [ Time Frame: Baseline (Day 28 of Visit 7) and end of treatment Period 2 (Day 43+1 of Visit 9) ]
   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.

Secondary Outcome Measures :

1. WOMAC Stiffness Domain Score [ 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 ]
   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.
2. WOMAC Physical Function Domain Score [ 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 ]
   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.
3. WOMAC Total Score [ 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 ]
   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.
4. Importance Weighted Total WOMAC Score [ 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 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.
5. Daily Diary Pain Score During Week 1 of Each Treatment Period [ 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 ]
   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).
6. Daily Diary Pain Score During Week 2 of Each Treatment Period [ 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 ]
   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).
7. Rescue Medication Use [ Time Frame: Day -7 (Visit 2) up to 28-day follow-up (Visit 10) ]
   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.
8. 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 ]
9. Urinary Leukotriene E4 (LTE4) Levels [ Time Frame: Day -7 (Visit 2) up to Day 43 (Visit 9 or End of Treatment Period 2) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

  Show 31 Study Locations

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01147458 History of Changes
• Other Study ID Numbers: B0041007
• First Posted: June 22, 2010
• Results First Posted: May 21, 2013
• Last Update Posted: June 6, 2013
• Last Verified: May 2013

Keywords provided by Pfizer:

Cross-over; safety; efficacy; tolerability; osteoarthritis; knee; pain

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Naproxen; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Gout Suppressants; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action