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

May 30, 2013 updated by: Pfizer

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
190

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Quebec, Canada, G1W 4R4
        • Pfizer Investigational Site
      • Quebec, Canada, G1V 3M7
        • Pfizer Investigational Site
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, A1A 3R5
        • Pfizer Investigational Site
    • Quebec
      • Sherbrooke, Quebec, Canada, J1H 1Z1
        • Pfizer Investigational Site
  • Sweden
      • Goteborg, Sweden, 413 45
        • Pfizer Investigational Site
      • Stockholm, Sweden, 115 22
        • Pfizer Investigational Site
  • United States
    • Arizona
      • Peoria, Arizona, United States, 85381
        • Pfizer Investigational Site
      • Phoenix, Arizona, United States, 85013
        • Pfizer Investigational Site
      • Phoenix, Arizona, United States, 85015
        • Pfizer Investigational Site
    • California
      • Anaheim, California, United States, 92801
        • Pfizer Investigational Site
      • Carmichael, California, United States, 95608
        • Pfizer Investigational Site
      • Fair Oaks, California, United States, 95628
        • Pfizer Investigational Site
      • San Diego, California, United States, 92128
        • Pfizer Investigational Site
    • Colorado
      • Denver, Colorado, United States, 80209
        • Pfizer Investigational Site
    • Florida
      • DeLand, Florida, United States, 32720
        • Pfizer Investigational Site
      • Pensacola, Florida, United States, 32504
        • Pfizer Investigational Site
      • South Miami, Florida, United States, 33143
        • Pfizer Investigational Site
    • Indiana
      • South Bend, Indiana, United States, 46601
        • Pfizer Investigational Site
    • Kansas
      • Overland Park, Kansas, United States, 66211
        • Pfizer Investigational Site
      • Overland Park, Kansas, United States, 66212
        • Pfizer Investigational Site
    • Massachusetts
      • Worcester, Massachusetts, United States, 01610
        • Pfizer Investigational Site
    • Minnesota
      • Edina, Minnesota, United States, 55435
        • Pfizer Investigational Site
      • St. Paul, Minnesota, United States, 55114
        • Pfizer Investigational Site
    • Nevada
      • Las Vegas, Nevada, United States, 89144
        • Pfizer Investigational Site
    • North Carolina
      • Monroe, North Carolina, United States, 28112
        • Pfizer Investigational Site
    • North Dakota
      • Fargo, North Dakota, United States, 58103
        • Pfizer Investigational Site
    • Ohio
      • Columbus, Ohio, United States, 43213
        • Pfizer Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Pfizer Investigational Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19139
        • Pfizer Investigational Site
    • Texas
      • Austin, Texas, United States, 78705
        • Pfizer Investigational Site
    • Virginia
      • Arlington, Virginia, United States, 22205
        • Pfizer Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
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: 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: PF-04191834 placebo
Matching PF-04191834 placebo tablets to be administered BID for two weeks
Drug: Naproxen
Naproxen 500 mg tablet administered BID for a total of four weeks
Experimental: Naproxen followed by PF-04191834+Naproxen
Naproxen 500 mg BID followed by PF-04191834 600 mg BID + Naproxen 500 mg BID
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
Naproxen 500 mg tablet administered BID for a total of four weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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
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.
Baseline (Day 28 of Visit 7) and end of treatment Period 2 (Day 43+1 of Visit 9)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
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
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.
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
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.
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
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.
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
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).
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
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).
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
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.
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
Pre-dose and post-dose (1 to 3 hours) on Days 1, 8, 15, 29, 36, and 43
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.
Day -7 (Visit 2) up to Day 43 (Visit 9 or End of Treatment Period 2)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 16, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 17, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 22, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 6, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 30, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • B0041007

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Osteoarthritis, Knee

Clinical Trials on PF-04191834

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings