Clinical trial NCT00689273: Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study In Subjects With Osteoarthritic Pain Of The Knee
Official title: A 2-WEEK, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED, PARALLEL-GROUP, PHASE 2, MULTICENTER STUDY OF PF-04136309 IN SUBJECTS WITH OSTEOARTHRITIC PAIN OF THE KNEE
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Keywords: PF-04136309 CCR2 osteoarthritic pain knee
phase 2 placebo multicenter double-blind placebo-controlled
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-06-03
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics in patients with osteoarthritic pain of the knee. The most painful knee joint will be identified as the index joint at screening, and this joint will be used for all pain assessments throughout the study.


Eligibility criteria: Inclusion Criteria:

* Male or female of any race, between the ages of 18 and 75 years inclusive
* Female subjects must be of non-childbearing potential and have a negative pregnancy test at Screening.
* Osteoarthritis of the knee of at least 6 months duration and meeting the American College of Rheumatology Criteria. For radiographic criteria the Xray must have been taken within the last 5 years. If none is available, one should be taken and the diagnostic criteria confirmed prior to randomization.
* Willing and able to discontinue all current analgesic therapy, including OTC pain medications and topical analgesics for OA pain, for period beginning with washout phase (lasting 2 days or 5 half-lives of patient's current analgesic medication prior to Day -6) and continuing for the entire duration of study. As an exception, acetaminophen may be used for non-joint related pain at doses ≤1 g/day at the discretion of a qualified member of the study team.
* If a subject has evidence or a history of clinically significant endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, renal, psychiatric, or neurological disease, the investigator must confirm that the disease is stable (at least 4 weeks) and under control.
* QTc interval ≤450 msec and a PR interval ≤210 msec on Screening ECG.

Exclusion Criteria:

* Pregnant or lactating females, and females of childbearing potential.
* Arthroscopy performed on index knee within 1 year of screening.
* Active depression as defined by or meeting The Hospital Anxiety and Depression Scale (HADS) of \>10.
* Unwillingness to refrain from consumption of grapefruit or grapefruit juice from 7 days prior to the first dose of study medication until completion of the study.
* First degree or higher AV block, defined as PR interval \>210 msecs, bundle branch block, fascicular block or intraventricular conduction delay or clinically relevant abnormality on screening ECG.
* 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).
* Symptomatic OA of the hip ipsilateral to index knee which the patient considers more painful than the knee.
* Use of prohibited medications as listed below, in the absence of appropriate washout period. The following analgesic agents must be discontinued within 48 hours or 5 half lives of the analgesic being washed out prior to the baseline period (Day -6 to Day 0);

  * NSAIDs and selective COX-2 inhibitors;
  * Acetaminophen ( as an exception acetaminophen may be used for non-joint related pain at doses ≤1g/day);
  * Opioids.
  * Oral or I/M corticosteroids within 4 weeks prior to screening. I/A steroids within 12 weeks prior to baseline in study joint or any other joints within 4 weeks prior to baseline, or I/A hyaluronic acid within 24 weeks prior to baseline;
  * Use of concomitant medications that are CYP3A inhibitors or CYP3A inducers, or that are P-glycoprotein substrates within 48 hours or 5 half lives prior to baseline.

Primary outcomes:
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Domain Score at Week 2
timeFrame: Baseline, Week 2
Secondary outcomes:
measure: Change From Baseline in WOMAC Pain Domain Score at Week 1
timeFrame: Baseline, Week 1
measure: Change From Baseline in WOMAC Stiffness Domain Score at Week 1 and Week 2
timeFrame: Baseline, Weeks 1, 2
measure: Change From Baseline in WOMAC Physical Function Domain Score at Week 1 and Week 2
timeFrame: Baseline, Weeks 1, 2
measure: Change From Baseline in WOMAC Total Score at Week 1 and Week 2
timeFrame: Baseline, Weeks 1, 2
measure: Change From Baseline in WOMAC Importance Weighted Total Score at Week 1 and Week 2
timeFrame: Baseline, Weeks 1, 2
measure: Change From Baseline in 11 Point Numeric Pain Rating Scale (NRS) at Week 1 and Week 2 (Weekly Average)
timeFrame: Baseline, Weeks 1, 2
measure: Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14
timeFrame: Baseline, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14
measure: Number of Participants With at Least a 30 Percent (%) and 50% Reduction in Average Weekly Pain Score at Week 2: Last Observation Carried Forward (LOCF)
timeFrame: Baseline, Week 2
measure: Change From Baseline in Patient's Global Assessment of Arthritic Condition at Week 1 and Week 2
timeFrame: Baseline, Weeks 1, 2
Other outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Baseline up to 30 days after last dose of study drug (up to Day 44)
measure: Number of Participants With Treatment Emergent Treatment Related AEs and SAEs
timeFrame: From Baseline up to 30 days after last dose of study drug (up to Day 44)
measure: Number of Participants Who Discontinued Due to Treatment Emergent AEs and Treatment Emergent Treatment Related AEs
timeFrame: From Baseline up to 30 days after last dose of study drug (up to Day 44)
measure: Number of Treatment-Emergent AEs by Severity
timeFrame: From Baseline up to 30 days after last dose of study drug (up to Day 44)
measure: Number of Treatment-Emergent Treatment-Related AEs by Severity
timeFrame: From Baseline up to 30 days after last dose of study drug (up to Day 44)
measure: Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity
timeFrame: From Baseline up to 30 days after last dose of study drug (up to Day 44)
measure: Number of Participants With Clinically Significant Change From Baseline in Blood Pressure and Pulse Rate
timeFrame: From Baseline up to Week 2
measure: Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters
timeFrame: Baseline up to Week 2
measure: Plasma Concentration Versus Time of PF-04136309
timeFrame: Day 1 and Day 14: Pre-dose and 6,7 hours post-dose
measure: Change From Baseline in Absolute Monocyte Count at Day 14
timeFrame: Baseline, Day 14
measure: Change From Baseline in Percent Monocytes at Day 14
timeFrame: Baseline, Day 14
Locations:
city: DeLand
country: United States
facility: University Clinical Research-DeLand, LLC
state: Florida
city: South Miami
country: United States
facility: Arthritis & Rheumatic Care Center
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Overland Park
country: United States
facility: Diagnostic Imaging Centers
state: Kansas
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
city: Madisonville
country: United States
facility: Commonwealth Biomedical Research, LLC
state: Kentucky
city: Chesterfield
country: United States
facility: Covenant Health and Wellness Center
state: Missouri
city: Creve Coeur
country: United States
facility: Metro Imaging West County
state: Missouri
city: Saint Peters
country: United States
facility: Metro Imaging St. Peters
state: Missouri
city: New York
country: United States
facility: Analgesic Development Limited
state: New York
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Warwick
country: United States
facility: Statcare
state: Rhode Island
city: San Antonio
country: United States
facility: Diagnostics Research Group
state: Texas
city: San Antonio
country: United States
facility: South Texas Radiology Group
state: Texas
city: Arlington
country: United States
facility: Commonwealth Orthopaedics and Rehabilitation PC
state: Virginia
city: Arlington
country: United States
facility: IntegraTrials, LLC
state: Virginia
city: Clarksburg
country: United States
facility: United Hospital Center Clinical Trials Office
state: West Virginia
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University College of Medicine
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: