Clinical trial NCT00521989: CRx-102 Osteoarthritis Multicenter Evaluation Trial
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Knee Osteoarthritis
Keywords: Osteoarthritis
Knee
CRx-102
prednisolone
dipyridamole
CombinatoRx
WOMAC
Lead sponsor: Zalicus
Sponsor class: INDUSTRY
First posted: 2007-08-29
Enrollment: 279
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline to Day 98 Using the WOMAC Pain Question #1
timeFrame: Baseline to Day 98
Secondary outcomes:
measure: 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.
timeFrame: Day 98
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Chandler
country: United States
state: Arizona
city: Mesa
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Tuscon
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Anaheim
country: United States
state: California
city: Rancho Mirage
country: United States
state: California
city: Upland
country: United States
state: California
city: Westlake Village
country: United States
state: California
city: Deland
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: Kissimee
country: United States
state: Florida
city: Largo
country: United States
state: Florida
city: Longwood
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Paducah
country: United States
state: Kentucky
city: Covington
country: United States
state: Louisiana
city: Towson
country: United States
state: Maryland
city: Brockton
country: United States
state: Massachusetts
city: Haverhill
country: United States
state: Massachusetts
city: Peabody
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Bingham Farms
country: United States
state: Michigan
city: Missoula
country: United States
state: Montana
city: Reno
country: United States
state: Nevada
city: Haddon Heights
country: United States
state: New Jersey
city: Voorhees
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: New York
country: United States
state: New York
city: Plainview
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Hickory
country: United States
state: North Carolina
city: High Point
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Fargo
country: United States
state: North Dakota
city: Cincinatti
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Mayfield Village
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Eugene
country: United States
state: Oregon
city: Duncansville
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: W. Reading
country: United States
state: Pennsylvania
city: Cumberland
country: United States
state: Rhode Island
city: Warwick
country: United States
state: Rhode Island
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Sandy
country: United States
state: Utah
city: Roanoke
country: United States
state: Virginia
city: Virginia Beach
country: United States
state: Virginia
city: Tacoma
country: United States
state: Washington
city: Kitchener
country: Canada
state: Ontario
Study officials:
affiliation: Zalicus
name: Margaret Lee, PhD
role: STUDY_DIRECTOR
References: