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-LO) INHIBITOR PF-04191834 ALONE AND IN COMBINATION WITH NAPROXEN IN PATIENTS WITH FLARE-ENRICHED OSTEOARTHRITIS OF THE KNEE

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2010-020475-23-SE
• Date of registration: 09/08/2010
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc.235 East 42nd Street, New York, NY 10017
• Public 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-LO) INHIBITOR PF-04191834 ALONE AND IN COMBINATION WITH NAPROXEN IN PATIENTS WITH FLARE-ENRICHED OSTEOARTHRITIS OF THE KNEE
• Scientific 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-LO) INHIBITOR PF-04191834 ALONE AND IN COMBINATION WITH NAPROXEN IN PATIENTS WITH FLARE-ENRICHED OSTEOARTHRITIS OF THE KNEE
• Date of first enrolment: 05/10/2010
• Target sample size: 190
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020475-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: yes Other trial design description: Double dummy, crossover If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Naproxen

Countries of recruitment

Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. 2. Male or female subjects between the ages of 18 and 75 years inclusive at the time of entering the study. 3. Diagnosis of OA of the knee based on American College of Rheumatology criteria with X-ray confirmation (a Kellgren-Lawrence X-ray grade of =229 with symptom duration for at least 3 months. X-rays taken within the last 12 months may be used for confirmation provided appropriate documentation is available. 4. Willing and able to discontinue all current analgesic therapy, including OTC pain medications and topical analgesics for OA pain, for period beginning at washout phase and continuing for the entire duration of study. 5. For subjects discontinuing background NSAIDs and COX-2 inhibitors only, an increase in NRS =1 during the placebo run-in prior to randomization at Visit 3.
6. Daily pain score =4 during the run-in in the last 3 daily diary assessments prior to
randomization. 7. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Body mass index (BMI) of >39 kg/m2. A BMI upper limit of 39.5 kg/m2 may be rounded down to 39.0 kg/m2 and will be acceptable for inclusion. 2. Clinical evidence of existing hepatic disease or a medical history of such a condition in the last year. Subjects with AST or ALT >ULN. Subjects with total bilirubin >ULN (except those with a documented history of Gilbert’s Syndrome). Subjects with AST/ALT/total bilitubin >ULN and <1.5X ULN may be retested once. 3. Pregnant or lactating females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception as outlined in this protocol from at least 14 days prior to the first dose of study medication through 28 days after the last dose of study drug. 4. Participation in a clinical trial for an investigational drug and/or agent within 30 days (or 5 half-lives, whichever is longer) prior to randomization.
5. Any history of alcohol or illicit drug abuse within 1 year of screening.
6. A positive urine drug screen. 7. Active malignancy of any type or history of a malignancy within 10 years (with the exception of subjects with a history of treated basal cell carcinoma or successful surgically treated stage 0/1 cervical cancer).
8. Symptomatic OA of the hip ipsilateral to index knee which the patient considers more painful than the knee. 9. Subjects with a history of HIV. 10. Subjects with a history of Hepatitis B or Hepatitis C infection, confirmed by hepatitis virus serology. 11. History of diseases other than OA that may involve the index knee, including: Inflammatory joint diseases, Crystalline diseases, Endocrinopathies, Metabolic diseases, Infections, Neuropathic disorders, Avascular necrosis, Paget’s disease, or Tumors, Symptomatic anserine bursitis or acute joint trauma of the index knee within 1 year, Arthroscopy performed on index knee within 1 year, Other severe pain that impairs the assessment of OA pain. 12. Any condition affecting drug absorption, eg, gastrectomy or any active GI disease (including any relevant surgery). 13. Active or history of peptic ulceration, erosive gastritis, gastrointestinal bleeding (two or more distinct episodes of proven ulceration or bleeding), or perforation. 14. Subjects with a history of coagulapathy or abnormal bleeding times. 15. Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. Patients with resting heart rate >100 or <50 bpm, first degree or higher AV block, defined as PR interval >210 msec, complete left or right bundle branch block or other clinically significant conduction abnormality, evidence of prior myocardial infarction, evidence of QTc prolongation (defined as >450 msec) or history of QTc prolongation, or any other clinically relevant abnormality on screening ECG. - If QTc is prolonged with the singlet measurement, the ECG should be repeated two more times and the average QTc of all three readings should be used to qualify the subject. 16. Known or previously exhibited hypersensitivity to the active substance naproxen (including naproxen sodium) or any of the excipients. 17. Any history of asthma, urticaria, or allergic-type reactions after taking acetylsalicylic acid (ASA) or other NSAIDs (ie, complete or partial syndrome of ASA-intolerancerhinosinusitis, urticaria/angioedema, nasal polyps, asthma). 18. Use of prohibited medications as listed below, in the absence of appro

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic pain in patients with Osteo-arthritis.
MedDRA version: 12.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis

Intervention(s)

Product Name: PF-04191834
Product Code: PF-04191834
Pharmaceutical Form: Film-coated tablet
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Naproxen
Pharmaceutical Form: Tablet
INN or Proposed INN: Naproxen
CAS Number: 22204-53-1
Other descriptive name: Naproxen
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: - To evaluate the efficacy of PF-04191834 versus placebo in relieving pain in patients with osteoarthritis of the knee.
- To evaluate the efficacy of PF-04191834 plus naproxen versus naproxen in relieving pain in patients with osteoarthritis of the knee.
- To evaluate the safety and tolerability of PF-04191834 (as monotherapy) in patients with osteoarthritis.
- To evaluate the safety and tolerability of PF-04191834 when co-administered with
naproxen in patients with osteoarthritis.

Secondary Objective: - To examine the pharmacokinetics of PF-04191834 in patients with osteoarthritis.
- To explore the relationship between urinary LTE4 levels as a biomarker of 5-LO
inhibition and efficacy of PF-04191834 in patients with osteoarthritis.
- To provide samples for exploratory research into the mechanism of action of
PF-04191834 and/or the disease (OA) under study.

Primary end point(s): Western Ontario & McMaster (WOMAC) Osteoarthritis Index (48 hour recall,
categorical version) Pain Score (Likert Scale, Range 0-20) in the more painful knee joint as identified at screening at the end of treatment period relative to baseline as follows:
PF-04191834 compared to placebo.
PF-04191834 + naproxen compared to naproxen.

Secondary ID(s)

B0041007