Clinical trial NCT00396955: A Study Comparing 4 Dose Regimens of PLA-695, Naproxen, and Placebo In Subjects With Osteoarthritis Of The Knee
Official title: A Multicenter, Randomized, Double-Blind Comparison of 4 Dose Regimens of Pla-695, Naproxen, and Placebo Administered Daily for 6 Weeks in Subjects With Active Osteoarthritis of the Knee
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Osteoarthritis
Keywords: osteoarthritis
arthritis
pain
Lead sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
Sponsor class: INDUSTRY
First posted: 2006-11-08
Enrollment: 560
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Objectives: Primary:To assess the efficacy and safety of PLA-695 in subjects with active osteoarthritis (OA) of the knee.

Secondary:To determine the pharmacokinetics (PK) and pharmacodynamics (PD) of PLA-695 among dose levels. To assess health outcome measures. To assess the effect of PLA-695 on biomarkers related to clinical responses. To assess PLA-695 exposure-response relationship on PD, efficacy, and safety measures. To assess pharmacogenomics (PGX) analysis in OA.

Detailed description: This is a multi-center, randomized, double-blind, double-dummy, parallel, placebo- and positive-control (naproxen), dose-ranging study to assess the efficacy and safety of 3 oral doses of PLA-695 administered QD and 1 dose of PLA-695 administered BID for 6 weeks. Subjects will be randomized to 1 of 6 treatment groups: PLA-695 50 mg, 200 mg, or 400 mg QD, PLA-695 200 mg BID, placebo, or naproxen 500 mg BID. Subjects will undergo a washout period of 2 to 14 days. The number of days for washout will be determined by the pre-study NSAID of each subject. Subjects who washout from previous therapy with an increase in signs and symptoms of OA will be randomly assigned to receive PLA-695.

Eligibility criteria: Inclusion Criteria: The main inclusion criteria is listed below, additional inclusion criteria is in the protocol.

* Men or women 50 to 75 years of age. Women must be of non-childbearing potential. Sexually active men who are not surgically sterile must agree and commit to use of barrier contraception during the study and for at least 12 weeks after the last dose of PLA.
* Diagnosed with idiopathic OA of the knee for at least 3 months duration in accordance with \[1986\] American College of Rheumatology (ACR) clinical and radiographic criteria: knee pain, the presence of osteophytes, and any one of the following: age \>50 years, crepitus, or morning stiffness \<30 minutes.
* Radiographic confirmation of OA at the target joint (weight-bearing anteroposterior and lateral views) within 1 year of screening.
* Must be currently treated for OA with a stable daily dose of 1 NSAID, including COX-2 inhibitors, not exceeding the maximum recommended dose in the product label, and taken as prescribed by the physician, starting at least 4 weeks before the screening visit.

Exclusion Criteria: These are some of the main exclusion criteria for the the study. Additional exclusion are included in the protocol.

* History of or suspected current esophageal or gastrointestinal bleeding, ulcers, obstruction, or perforation, or pancreatitis.
* Grade 4 severity on the Kellgren-Lawrence Scale on the screening target knee radiograph.
* Any significant cardiovascular, hematologic, blood dyscrasia, endocrine, respiratory, neurologic, psychiatric, metabolic, immunologic, infectious, hepatic, or renal condition that the investigator considers detrimental to the subject's participating in the study or that may prevent the successful completion of the study.
* Any clinically significant laboratory abnormality.

Primary outcomes:
measure: WOMAC VAS walking pain (question 1) at week 6 is the primary endpoint.
Secondary outcomes:
measure: WOMAC VAS walking pain at weeks 1, 2, 3, 4, and 5; WOMAC pain, stiffness, and function subscales, and composite score; Investigatorsâ Efficacy Evaluation; Investigatorsâ overall assessment; Joint tenderness. Subjectsâ Efficacy Evaluation.
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Palo Alto
country: United States
state: California
city: Rancho Mirage
country: United States
state: California
city: Santa Maria
country: United States
state: California
city: Upland
country: United States
state: California
city: Delray Beach
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: South Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Idaho Falls
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Wichita
country: United States
state: Kansas
city: Baltimore
country: United States
state: Maryland
city: Frederick
country: United States
state: Maryland
city: Fall River
country: United States
state: Massachusetts
city: Kalamazoo
country: United States
state: Michigan
city: St. Louis
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Dover
country: United States
state: New Hampshire
city: Mamaroneck
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Duncansville
country: United States
state: Pennsylvania
city: West Reading
country: United States
state: Pennsylvania
city: Willow Grove
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Capital Federal
country: Argentina
state: Buenos Aires
city: Capital Federal
country: Argentina
state: Buenos Aires
city: Cordoba-Capital
country: Argentina
state: Cordoba
city: San Miguel de Tucuman
country: Argentina
state: Tucuman
city: Sao Paulo
country: Brazil
city: Coquitlam
country: Canada
state: British Columbia
city: Kelowna
country: Canada
state: British Columbia
city: Langley
country: Canada
state: British Columbia
city: Penticton
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Hamilton
country: Canada
state: Ontario
city: Kitchener
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Sarnia
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Pointe-Claire
country: Canada
state: Quebec
city: Trois-Rivieres
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Hong Kong
country: Hong Kong
city: Bekescsaba
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Kiskunhalas
country: Hungary
city: Nyiregyhaza
country: Hungary
city: Guadalajara
country: Mexico
state: Jalisco
city: Monterrey
country: Mexico
state: Nuevo Leon
city: Mexico City
country: Mexico
city: Almere
country: Netherlands
city: Geleen
country: Netherlands
city: Hertogenbosch
country: Netherlands
city: Nijmegen
country: Netherlands
city: Krakow
country: Poland
city: Krakow
country: Poland
city: Szczecin
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Guadalajara
country: Spain
city: La Coruna
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
Study officials:
affiliation: Wyeth is now a wholly owned subsidiary of Pfizer
name: Medical Monitor
role: STUDY_DIRECTOR
affiliation: For Argentina, Scheima@wyeth.com
name: Trial Manager
role: PRINCIPAL_INVESTIGATOR
affiliation: For Brazil, xavierl@wyeth.com
name: Trial Manager
role: PRINCIPAL_INVESTIGATOR
affiliation: For China, medinfo@wyeth.com
name: Trial Manager
role: PRINCIPAL_INVESTIGATOR
affiliation: For Hong Kong, medinfo@wyeth.com
name: Trial Manager
role: PRINCIPAL_INVESTIGATOR
affiliation: For Hungary, WPBUMED@wyeth.com
name: Trial Manager
role: PRINCIPAL_INVESTIGATOR
affiliation: For Mexico, gomezzlj@wyeth.com
name: Trial Manager
role: PRINCIPAL_INVESTIGATOR
affiliation: For Netherlands, trials-NL@wyeth.com
name: Trial Manager
role: PRINCIPAL_INVESTIGATOR
affiliation: For Poland, WPWZMED@wyeth.com
name: Trial Manager
role: PRINCIPAL_INVESTIGATOR
affiliation: For Spain, infomed@wyeth.com
name: Trial Manager
role: PRINCIPAL_INVESTIGATOR
References: