A Study Comparing 4 Dose Regimens of PLA-695, Naproxen, and Placebo In Subjects With Osteoarthritis Of The Knee

Osteoarthritis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00396955
• Other study ID #: 3175A1-202
• Status: Terminated
• Phase: Phase 2
• First received: November 7, 2006
• Last updated: December 19, 2007
• Start date: November 2006
• Est. completion date: November 2007

Study information

• Verified date: December 2007
• Source: Wyeth is now a wholly owned subsidiary of Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in ResearchBrazil: Ministry of HealthCanada: Ethics Review CommitteeCanada: Health CanadaChina: Ministry of HealthFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Institutional Ethical CommitteeFrance: Ministry of HealthFrance: National Consultative Ethics Committee for Health and Life SciencesHong Kong: Department of HealthHong Kong: Joint CUHK-NTEC Clinical Research Ethics CommitteeHungary: National Institute of PharmacyMexico: Ethics CommitteeMexico: Federal Commission for Protection Against Health RisksNetherlands: Independent Ethics CommitteeNetherlands: Medical Ethics Review Committee (METC)Poland: Ministry of HealthSpain: Ministry of HealthSpain: Ministry of Health and ConsumptionUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 560
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• PLA-695

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Wyeth is now a wholly owned subsidiary of Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Hong Kong,  Hungary,  Mexico,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	WOMAC VAS walking pain (question 1) at week 6 is the primary endpoint.
Secondary	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.