CRx-102 Osteoarthritis Multicenter Evaluation Trial (COMET-1)

March 26, 2014 updated by: Zalicus

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy of CRx-102 in Subjects With Symptomatic Knee Osteoarthritis and Optional One-Year Extension

CRx-102 is a synergistic combination drug candidate containing the cardiovascular drug dipyridamole and a very low dose of the glucocorticoid prednisolone. CRx-102 is believed to work through a novel mechanism of action in which dipyridamole selectively amplifies the anti-inflammatory and immunomodulatory activities of the glucocorticoid without replicating the dose-dependent adverse effects.

CRx-102 has been associated with clinical benefit in proof of concept studies in subjects with hand OA and RA. This is the first study to explore the efficacy of CRx-102 in knee OA. It is considered a dose-finding study and will also compare the potential benefits of CRx-102 treatment to both prednisolone administered alone and to placebo in this indication.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

279

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Kitchener, Ontario, Canada
  • United States
    • Alabama
      • Huntsville, Alabama, United States
    • Arizona
      • Chandler, Arizona, United States
      • Mesa, Arizona, United States
      • Phoenix, Arizona, United States
      • Tuscon, Arizona, United States
    • Arkansas
      • Little Rock, Arkansas, United States
    • California
      • Anaheim, California, United States
      • Rancho Mirage, California, United States
      • Upland, California, United States
      • Westlake Village, California, United States
    • Florida
      • Deland, Florida, United States
      • Jupiter, Florida, United States
      • Kissimee, Florida, United States
      • Largo, Florida, United States
      • Longwood, Florida, United States
      • Palm Harbor, Florida, United States
      • Sarasota, Florida, United States
      • Tampa, Florida, United States
    • Georgia
      • Atlanta, Georgia, United States
    • Kentucky
      • Paducah, Kentucky, United States
    • Louisiana
      • Covington, Louisiana, United States
    • Maryland
      • Towson, Maryland, United States
    • Massachusetts
      • Brockton, Massachusetts, United States
      • Haverhill, Massachusetts, United States
      • Peabody, Massachusetts, United States
      • Worcester, Massachusetts, United States
    • Michigan
      • Bingham Farms, Michigan, United States
    • Montana
      • Missoula, Montana, United States
    • Nevada
      • Reno, Nevada, United States
    • New Jersey
      • Haddon Heights, New Jersey, United States
      • Voorhees, New Jersey, United States
    • New Mexico
      • Albuquerque, New Mexico, United States
    • New York
      • New York, New York, United States
      • Plainview, New York, United States
      • Rochester, New York, United States
    • North Carolina
      • Hickory, North Carolina, United States
      • High Point, North Carolina, United States
      • Winston-Salem, North Carolina, United States
    • North Dakota
      • Fargo, North Dakota, United States
    • Ohio
      • Cincinatti, Ohio, United States
      • Dayton, Ohio, United States
      • Mayfield Village, Ohio, United States
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
    • Oregon
      • Eugene, Oregon, United States
    • Pennsylvania
      • Duncansville, Pennsylvania, United States
      • Pittsburgh, Pennsylvania, United States
      • W. Reading, Pennsylvania, United States
    • Rhode Island
      • Cumberland, Rhode Island, United States
      • Warwick, Rhode Island, United States
    • Texas
      • Dallas, Texas, United States
      • Houston, Texas, United States
      • San Antonio, Texas, United States
    • Utah
      • Bountiful, Utah, United States
      • Sandy, Utah, United States
    • Virginia
      • Roanoke, Virginia, United States
      • Virginia Beach, Virginia, United States
    • Washington
      • Tacoma, Washington, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subject must voluntarily give written informed consent
  • Subject must be ≥ 40 years of age
  • Knee pain for at least 6 months requiring NSAIDs or Coxibs for analgesia on the majority of days (≥ 15 days) during the preceding month
  • WOMAC pain score when walking on a flat surface (question #1) between 30-80 mm at Screening with at least a 10 mm increase following NSAID or Coxib discontinuation during the Screening period
  • Radiographic evidence of knee OA (Kellgren-Lawrence grade 2 or 3)
  • Functional class I, II, or III according to the American Rheumatism Association
  • Subject willing to take a multivitamin or the equivalent of at least 400 IU vitamin D and the equivalent of at least 1000 mg of elemental calcium daily

Exclusion Criteria:

  • Predominant patellofemoral disease or clinically significant trauma to index knee
  • History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, osteoporotic and/or other major disease
  • History of malignancy within the past 10 years (except for excised or treated basal cell or fewer than 3 squamous cell skin carcinomas)
  • History of lymphoma or chronic leukemia
  • Moles or lesions that are currently undiagnosed, but are suspicious for malignancy
  • Surgery within the previous 3 months (except for minor dental, and/or cosmetic procedures)
  • History of drug or alcohol abuse (as defined by the Investigator)
  • History of bleeding disorder
  • History of GI bleeding within 5 years of Screening
  • History of severe migraines or headaches
  • History of glaucoma
  • Visually compromising cataract
  • Active diabetic retinopathy
  • History of osteoporotic fracture
  • History of opportunistic infection
  • Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 months prior to Screening
  • Fever or symptomatic viral or bacterial infection within 2 weeks prior to Screening
  • Positive for hepatitis C (HCV) antibody
  • Positive for hepatitis B surface antigen (HBsAg)
  • Known positive history for human immunodeficiency virus (HIV) antibody
  • Surgery on the index knee within 1 year of Screening
  • History of hypersensitivity to steroids or dipyridamole
  • Treatment with oral, intramuscular, or intravenous glucocorticoids within 6 weeks prior to Screening; intra-articular glucocorticoids within 10 weeks prior to Screening; inhaled glucocorticoid is permitted
  • Treatment with injectable hyaluronic acid within 3 months of Screening
  • Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 30 days prior to Screening
  • Treatment with NSAIDs (oral or topical), Coxibs or topical capsaicin
  • Treatment with anticoagulants including: dipyridamole, warfarin, clopidogrel, ticlopidine, or ASA > 81 mg per day
  • Treatment with any concomitant medications that have not been at a stable dose for at least 28 days prior to Screening
  • Treatment for osteoporosis such as bisphosphonates (e.g., Fosamax®, Actonel®), or teriparatide (e.g., Forteo®), or calcitonin (e.g., Miacalcin, Calcimar) must be at stable dosages for at least 3 months prior to Screening
  • ALT or AST laboratory values >1.5 X the ULN
  • HgbA1c value of >7.0%
  • Current enrollment in any other study with investigational drug or device
  • Female subject who is pregnant or lactating
  • Unwilling or unable to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's return for follow-up visits on schedule
  • Other unspecified reasons that, in the opinion of the Investigator or sponsor make the subject unsuitable for enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CRx-102 (2.7/90)

2.7 mg prednisolone plus 90 mg dipyridamole

Subjects were dose twice daily through day 98. Prednisolone at 2.7 mg/d was administered as 1.8 mg at 8AM and 0.9 mg at 1PM. The dipyridamole dose was divided equally between the two time points, 8AM and 1PM
Drug: CRx-102 (2.7/90)
CRx-102 dose 1
Other Names:
  • 2.7 mg prednisolone plus 90 mg dipyridamole
Experimental: CRx-102 (2.7/180)

2.7 mg prednisolone plus 180 mg dipyridamole

Subjects were dose twice daily through day 98. Prednisolone at 2.7 mg/d was administered as 1.8 mg at 8AM and 0.9 mg at 1PM. The dipyridamole dose was divided equally between the two time points, 8AM and 1PM
Drug: CRx-102 (2.7/180)
CRx-102 dose 2
Other Names:
  • Prednisolong 2.7 mg plus dipyridamole 180 mg
Experimental: CRx-102 (2.7/360)

2.7 mg prednisolone plus 360 mg dipyridamole

Subjects were dose twice daily through day 98. Prednisolone at 2.7 mg/d was administered as 1.8 mg at 8AM and 0.9 mg at 1PM. The dipyridamole dose was divided equally between the two time points, 8AM and 1PM
Drug: CRx-102 (2.7/90)
CRx-102 dose 1
Other Names:
  • 2.7 mg prednisolone plus 90 mg dipyridamole
Drug: CRx-102 (2.7/360)
CRx-102 dose 3
Other Names:
  • 2.7 mg prednisolone plus 360 mg dipyridamole
Active Comparator: Prednisolone

2.7 mg prednisolone

Subjects were dose twice daily through day 98. Prednisolone at 2.7 mg/d was administered as 1.8 mg at 8AM and 0.9 mg at 1PM.
Drug: Prednisolone
Prednisolone
Other Names:
  • 2.7 mg prednisolone
Placebo Comparator: Placebo

Placebo

Subjects were dose twice daily through day 98.
Drug: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Day 98 Using the WOMAC Pain Question #1
Time Frame: Baseline to Day 98
The WOMAC Index is a validated, 24-question self-administered assessment of three dimensions of pain, stiffness, and physical function for subjects with knee or hip OA. The WOMAC pain question #1 asks subjects to "think about the pain you felt in your (study joint) caused by your arthritis during the last 48 hours when walking on a flat surface." This is a visual analog scale (VAS) where the subject indicates pain severity by making a mark through a 100 mm horizontal line with "No Pain" on the left (0 mm) and "Extreme Pain" on the right (100 mm). The distance between the left end of the scale and the subject's mark is measured in millimeters. Lower values represent a better outcome.
Baseline to Day 98

Secondary Outcome Measures

Outcome Measure
Time Frame
To Assess the Efficacy of the CRx-102 Compared to Placebo on the Change From Baseline to Day 98 Using the Full WOMAC Pain, Stiffness, Physical Function Parameters, and Patient Global Assessment VAS.
Time Frame: Day 98
Day 98

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zalicus

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

July 1, 2009

Study Completion (Actual)

July 1, 2009

Study Registration Dates

First Submitted

August 27, 2007

First Submitted That Met QC Criteria

August 27, 2007

First Posted (Estimate)

August 29, 2007

Study Record Updates

Last Update Posted (Estimate)

April 29, 2014

Last Update Submitted That Met QC Criteria

March 26, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRx-102-006

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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