A Study To Investigate Whether PF-04457845 Is Effective In Treating Pain, Is Safe And Tolerable In Patients With Osteoarthritis Of The Knee

Study Overview
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Brief Summary
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Inactivation of the FAAH (Fatty Acid Amide Hydrolase) enzyme has been shown to relieve pain and inflammation in animal studies. PF-04457845 has been shown to inactivate the FAAH enzyme in animals and healthy human volunteers. The purpose of this study is to evaluate whether PF-04457845 can inactivate the FAAH enzyme in patients experiencing pain due to OA and whether this results in these patients experiencing less pain.

Official Title
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A Phase 2a Randomized, Double-blinded, Double Dummy, Placebo And Active Controlled, Two-way Cross-over, Flare-enriched Multi-centre Clinical Trial To Examine The Pain Relief Produced By 2 Weeks Of Daily Oral Administration Of A Fatty Acid Amide Hydrolase (Faah) Inhibitor Pf-04457845 In Patients With Osteoarthritis Of The Knee.

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: PF-04457845
* Drug: PF-04457845
* Drug: Naproxen
* Drug: Naproxen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have a diagnosis of Osteoarthritis (OA) of the knee confirmed by X-ray Subjects must be willing and able to stop all current pain therapy for the duration of study. (Limited and specific pain therapy will be available throughout the study) Subjects can be male or female between the ages of 18 and 75 years inclusive, but female subjects must not be able become pregnant Exclusion Criteria: Subjects must not have any condition or medical history that might interfere with their ability to complete the study assessments

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04457845 followed by placebo<br> | Drug: PF-04457845<br>* PF-04457845 4 mg tablet once daily / matched placebo<br>|
| Experimental: Placebo followed by PF-04457845<br> | Drug: PF-04457845<br>* PF-04457845 4 mg tablet once daily / matched placebo<br>|
| Active Comparator: Naproxen followed by placebo<br> | Drug: Naproxen<br>* Naproxen 500 mg tablet twice daily / matched placebo<br>|
| Active Comparator: Placebo followed by Naproxen<br> | Drug: Naproxen<br>* Naproxen 500 mg tablet twice daily / matched placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of PF-04457845 (administered QD) versus placebo in relieving pain as measured by the WOMAC Pain sub-score in patients with osteoarthritis of the knee |  | 8 weeks | 
| To evaluate the safety and tolerability of PF-04457845 in patients with osteoarthritis. |  | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of PF-04457845 (administered QD) versus placebo as measured by the WOMAC Stiffness domain score (Likert scale for 2 items, overall score ranges from 0-8) in patients with osteoarthritis of the knee. |  | 8 weeks | 
| Efficacy of PF-04457845 (administered QD) versus placebo as measured by the WOMAC Physical Function domain score (Likert scale for 17 items, overall score ranges from 0-68) in patients with osteoarthritis of the knee. |  | 8 weeks | 
| Efficacy of PF-04457845 (administered QD) versus placebo as measured by the WOMAC Total Score in patients with osteoarthritis of the knee. |  | 8 weeks | 
| Efficacy of PF-04457845 (administered QD) versus placebo as measured by the Importance weighted Total WOMAC score in patients with osteoarthritis of the knee. |  | 8 weeks | 
| Efficacy of PF-04457845 (administered QD) versus placebo as measured by the Daily pain diary over weeks 1 and 2 of each treatment period using an 11-point Numeric Rating Scale (NRS) in patients with osteoarthritis of the knee. |  | 8 weeks | 
| Efficacy of PF-04457845 (administered QD) versus placebo as measured by the Subjects' use of rescue medication on either treatment. |  | 8 weeks | 
| Summary of plasma concentrations of PF-04457845. |  | 8 weeks | 
| Residual FAAH activity in leukocytes for subjects recruited prior to the interim analysis. |  | 8 weeks | 
| Plasma fatty acid amide levels (OEA, PEA, LEA and AEA) for subjects recruited prior to the interim analysis. |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cross-over evaluate the efficacy of PF-04457845 in relieving pain due to osteoarthritis OA knee osteoarthritis of knee pain due to osteoarthritis