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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01147458
First received: June 16, 2010
Last updated: May 30, 2013
Last verified: May 2013
  Purpose

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 Intervention Phase
Osteoarthritis, Knee
Drug: PF-04191834
Drug: PF-04191834 placebo
Drug: Naproxen placebo
Drug: Naproxen
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).

  • Rescue Medication Use [ Time Frame: Day -7 (Visit 2) up to 28-day follow-up (Visit 10) ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
  • Urinary Leukotriene E4 (LTE4) Levels [ Time Frame: Day -7 (Visit 2) up to Day 43 (Visit 9 or End of Treatment Period 2) ] [ Designated as safety issue: No ]
    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.


Enrollment: 190
Study Start Date: July 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01147458

  Show 31 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01147458     History of Changes
Other Study ID Numbers: B0041007
Study First Received: June 16, 2010
Results First Received: December 21, 2012
Last Updated: May 30, 2013
Health Authority: United States: Food and Drug Administration

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
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gout Suppressants
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 26, 2014