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

This study has been terminated.
(CRx-102-006 study results, negative)
Sponsor:
Information provided by (Responsible Party):
Zalicus
ClinicalTrials.gov Identifier:
NCT00521989
First received: August 27, 2007
Last updated: March 26, 2014
Last verified: March 2014
  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: CRx-102 (2.7/90)
Drug: Prednisolone
Drug: Placebo
Drug: CRx-102 (2.7/180)
Drug: CRx-102 (2.7/360)
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:
  • Change From Baseline to Day 98 Using the WOMAC Pain Question #1 [ Time Frame: Baseline to Day 98 ] [ Designated as safety issue: No ]
    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.


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 ]

Enrollment: 279
Study Start Date: August 2007
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 2.7 mg prednisolone plus 90 mg dipyridamole
Drug: CRx-102 (2.7/360)
CRx-102 dose 3
Other Name: 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 Name: 2.7 mg prednisolone
Placebo Comparator: Placebo

Placebo

Subjects were dose twice daily through day 98.

Drug: Placebo
Placebo
Other Name: 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 58 Study Locations
Sponsors and Collaborators
Zalicus
Investigators
Study Director: Margaret Lee, PhD Zalicus
  More Information

No publications provided

Responsible Party: Zalicus
ClinicalTrials.gov Identifier: NCT00521989     History of Changes
Other Study ID Numbers: CRx-102-006
Study First Received: August 27, 2007
Results First Received: February 10, 2014
Last Updated: March 26, 2014
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, Knee
Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Dipyridamole
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on September 16, 2014