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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by Zalicus.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Zalicus
ClinicalTrials.gov Identifier:
NCT00521989
First received: August 27, 2007
Last updated: February 26, 2009
Last verified: February 2009
  Purpose

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.


Condition Intervention Phase
Knee Osteoarthritis
Drug: prednisolone + dipyridamole
Drug: Prednisolone
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Zalicus:

Primary Outcome Measures:
  • To assess the efficacy of CRx-102 compared to placebo on the change from Baseline to Day 98 using the WOMAC pain question measuring pain when walking on a flat surface (question #1). [ Time Frame: Day 98 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: August 2007
Estimated Study Completion Date: September 2009
Estimated Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
CRx-102 (Dose 1)
Drug: prednisolone + dipyridamole
CRx-102 (Dose 1), CRx-102 (Dose 2), CRx-102 (Dose 3)
Experimental: 2
CRx-102 (Dose 2)
Drug: prednisolone + dipyridamole
CRx-102 (Dose 1), CRx-102 (Dose 2), CRx-102 (Dose 3)
Experimental: 3
CRx-102 (Dose 3)
Drug: prednisolone + dipyridamole
CRx-102 (Dose 1), CRx-102 (Dose 2), CRx-102 (Dose 3)
Active Comparator: 4
Prednisolone
Drug: Prednisolone
Prednisolone
Placebo Comparator: 5
Placebo
Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00521989

  Show 58 Study Locations
Sponsors and Collaborators
Zalicus
  More Information

No publications provided

Responsible Party: Medical Monitor, CombinatoRx
ClinicalTrials.gov Identifier: NCT00521989     History of Changes
Other Study ID Numbers: CRx-102-006
Study First Received: August 27, 2007
Last Updated: February 26, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Zalicus:
Osteoarthritis
Knee
CRx-102
prednisolone
dipyridamole
CombinatoRx
WOMAC

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Dipyridamole
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Vasodilator Agents
Cardiovascular Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 17, 2014