CRx-102 Osteoarthritis Multicenter Evaluation Trial

NCT ID: NCT00521989

Last Updated: 2014-04-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 279 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2009-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

CRx-102 (2.7/90)

Intervention Type: DRUG

CRx-102 dose 1

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

Group Type: EXPERIMENTAL

CRx-102 (2.7/180)

Intervention Type: DRUG

CRx-102 dose 2

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

Group Type: EXPERIMENTAL

CRx-102 (2.7/90)

Intervention Type: DRUG

CRx-102 dose 1

CRx-102 (2.7/360)

Intervention Type: DRUG

CRx-102 dose 3

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.

Group Type: ACTIVE_COMPARATOR

Prednisolone

Intervention Type: DRUG

Prednisolone

Placebo

Placebo

Subjects were dose twice daily through day 98.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

CRx-102 (2.7/90)

CRx-102 dose 1

Intervention Type: DRUG

Prednisolone

Prednisolone

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

CRx-102 (2.7/180)

CRx-102 dose 2

Intervention Type: DRUG

CRx-102 (2.7/360)

CRx-102 dose 3

Intervention Type: DRUG

Other Intervention Names

2.7 mg prednisolone plus 90 mg dipyridamole; 2.7 mg prednisolone; Prednisolong 2.7 mg plus dipyridamole 180 mg; 2.7 mg prednisolone plus 360 mg dipyridamole

Eligibility 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zalicus

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Margaret Lee, PhD

Role: STUDY_DIRECTOR

Zalicus

Locations

Huntsville, Alabama, United States

Chandler, Arizona, United States

Mesa, Arizona, United States

Phoenix, Arizona, United States

Tuscon, Arizona, United States

Little Rock, Arkansas, United States

Anaheim, California, United States

Rancho Mirage, California, United States

Upland, California, United States

Westlake Village, California, United States

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

Atlanta, Georgia, United States

Paducah, Kentucky, United States

Covington, Louisiana, United States

Towson, Maryland, United States

Brockton, Massachusetts, United States

Haverhill, Massachusetts, United States

Peabody, Massachusetts, United States

Worcester, Massachusetts, United States

Bingham Farms, Michigan, United States

Missoula, Montana, United States

Reno, Nevada, United States

Haddon Heights, New Jersey, United States

Voorhees Township, New Jersey, United States

Albuquerque, New Mexico, United States

New York, New York, United States

Plainview, New York, United States

Rochester, New York, United States

Hickory, North Carolina, United States

High Point, North Carolina, United States

Winston-Salem, North Carolina, United States

Fargo, North Dakota, United States

Cincinnati, Ohio, United States

Dayton, Ohio, United States

Mayfield Village, Ohio, United States

Oklahoma City, Oklahoma, United States

Eugene, Oregon, United States

Duncansville, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

West Reading, Pennsylvania, United States

Cumberland, Rhode Island, United States

Warwick, Rhode Island, United States

Dallas, Texas, United States

Houston, Texas, United States

San Antonio, Texas, United States

Bountiful, Utah, United States

Sandy City, Utah, United States

Roanoke, Virginia, United States

Virginia Beach, Virginia, United States

Tacoma, Washington, United States

Kitchener, Ontario, Canada

Countries

United States; Canada

Other Identifiers

CRx-102-006

Identifier Type: -

Identifier Source: org_study_id