CRx-102 Osteoarthritis Multicenter Evaluation Trial

NCT00521989 | Terminated Phase 2 Results DMC

• 1 other identifier: CRx-102-006
• Study Type: interventional
• Target: 279
• Locations: 2 countries
• Sites: 58

Brief Summary

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.

Conditions

Knee Osteoarthritis

Keywords

Osteoarthritis; Knee; CRx-102; prednisolone; dipyridamole; CombinatoRx; WOMAC

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Day 98 Using the WOMAC Pain Question #1

  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 Outcomes (1)

• 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.

  Day 98

Study Arms (5)

CRx-102 (2.7/90)

EXPERIMENTAL

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 (2.7/180)

EXPERIMENTAL

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 (2.7/360)

EXPERIMENTAL

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); Drug: CRx-102 (2.7/360)

Prednisolone

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

Placebo Subjects were dose twice daily through day 98.

Drug: Placebo

Interventions

CRx-102 (2.7/90) DRUG

CRx-102 dose 1

Also known as: 2.7 mg prednisolone plus 90 mg dipyridamole

CRx-102 (2.7/360); CRx-102 (2.7/90)

Prednisolone DRUG

Prednisolone

Also known as: 2.7 mg prednisolone

Prednisolone

Placebo DRUG

Placebo

Placebo

CRx-102 (2.7/180) DRUG

CRx-102 dose 2

Also known as: Prednisolong 2.7 mg plus dipyridamole 180 mg

CRx-102 (2.7/180)

CRx-102 (2.7/360) DRUG

CRx-102 dose 3

Also known as: 2.7 mg prednisolone plus 360 mg dipyridamole

CRx-102 (2.7/360)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Zalicus: lead

Study Sites (58)

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Huntsville, Alabama, United States

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Chandler, Arizona, United States

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Mesa, Arizona, United States

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Phoenix, Arizona, United States

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Tuscon, Arizona, United States

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Little Rock, Arkansas, United States

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Anaheim, California, United States

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Rancho Mirage, California, United States

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Upland, California, United States

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Westlake Village, California, United States

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DeLand, Florida, United States

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Jupiter, Florida, United States

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Kissimee, Florida, United States

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Largo, Florida, United States

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Longwood, Florida, United States

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Palm Harbor, Florida, United States

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Sarasota, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Paducah, Kentucky, United States

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Covington, Louisiana, United States

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Towson, Maryland, United States

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Brockton, Massachusetts, United States

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Haverhill, Massachusetts, United States

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Peabody, Massachusetts, United States

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Worcester, Massachusetts, United States

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Bingham Farms, Michigan, United States

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Missoula, Montana, United States

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Reno, Nevada, United States

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Haddon Heights, New Jersey, United States

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Voorhees Township, New Jersey, United States

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Albuquerque, New Mexico, United States

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New York, New York, United States

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Plainview, New York, United States

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Rochester, New York, United States

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Hickory, North Carolina, United States

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High Point, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Fargo, North Dakota, United States

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Cincinnati, Ohio, United States

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Dayton, Ohio, United States

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Mayfield Village, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Eugene, Oregon, United States

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Duncansville, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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West Reading, Pennsylvania, United States

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Cumberland, Rhode Island, United States

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Warwick, Rhode Island, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Bountiful, Utah, United States

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Sandy City, Utah, United States

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Roanoke, Virginia, United States

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Virginia Beach, Virginia, United States

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Tacoma, Washington, United States

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Kitchener, Ontario, Canada

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MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

dipyridamole, prednisolone drug combination; Prednisolone; Dipyridamole

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Margaret Lee, PhD
• Organization: Zalicus

mlee@zalicus.com

617-301-7142

Study Officials

• Margaret Lee, PhD

  Zalicus

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2007
• First Posted: August 29, 2007
• Study Start: August 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: April 29, 2014
• Results First Posted: April 29, 2014

Record last verified: 2014-03

Locations

US (57); CA (1)