Multicenter Study to Evaluate CRx-102 vs. Each of Its Components to Treat Active Rheumatoid Arthritis

NCT ID: NCT00551707

Last Updated: 2014-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2009-01-31

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 Osteoarthritis (OA) and Rheumatoid Arthritis (RA).

In this trial, CRx-102 will be given to subjects with active RA as an add-on therapy to existing stable doses of Disease Modifying Anti-Rheumatic Drugs (DMARDs) including methotrexate (MTX), sulfasalazine, hydroxychloroquine, leflunomide or azathioprine. MTX in combination with other DMARDs (e.g., sulfasalazine or hydroxychloroquine) will be permitted to reflect the current standard of care practices within rheumatology.

Detailed Description

The study was discontinued before the enrollment objective was met. Preliminary review of the efficacy dataset revealed that the efficacy dataset was not robust enough to support an extensive formal efficacy analysis as described in the SAP. Therefore, only the CRP values over time and the percent change in C-reactive protein (CRP) values in the As-Treated population were calculated.

Conditions

Rheumatoid Arthritis

Study Design

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

Study Groups

CRx-102 (2.7/180)

CRx-102 dose 1 total daily dose during treatment period (days 14-98) 2.7 mg prednisolone plus 180 mg dipyridamole administered as 1.8 mg prednisolone plus 90 mg dipyridamole at 8 AM and 0.9 mg prednisolone plus 90 mg dipyridamole at 1 PM titration dose (days 0-13) 2.7 mg prednisolone plus 90 mg dipyridamole administered as 1.8 mg prednisolone plus 45 mg dipyridamole at 8 AM and 0.9 mg prednisolone plus 45 mg dipyridamole at 1 PM

Group Type: EXPERIMENTAL

CRx-102 (2.7/180)

Intervention Type: DRUG

prednisolone 2.7 mg plus dipyridamole 180 mg

CRx-102 (2.7/360)

CRx-102 Dose 2 total daily dose during treatment period (days 14-98) 2.7 mg prednisolone plus 360 mg dipyridamole administered as 1.8 mg prednisolone plus 180 mg dipyridamole at 8 AM and 0.9 mg prednisolone plus 180 mg dipyridamole at 1 PM titration dose 1 (days 0-6) 2.7 mg prednisolone plus 90 mg dipyridamole administered as 1.8 mg prednisolone plus 45 mg dipyridamole at 8 AM and 0.9 mg prednisolone plus 45 mg dipyridamole at 1 PM titration dose 2 (days 7-13) 2.7 mg prednisolone plus 180 mg dipyridamole administered as 1.8 mg prednisolone plus 90 mg dipyridamole at 8 AM and 0.9 mg prednisolone plus 90 mg dipyridamole at 1 PM

Group Type: EXPERIMENTAL

CRx-102 (2.7/180)

Intervention Type: DRUG

prednisolone 2.7 mg plus dipyridamole 180 mg

CRx-102 (2.7/360)

Intervention Type: DRUG

Prednisolone 2.7 mg plus Dipyridamole 360 mg

Prednisolone

treatment dose ( days 0-98) total daily dose of 2.7 mg prednisolone administered as 1.8 mg prednisolone at 8 AM and 0.9 mg prednisolone at 1 PM

Group Type: ACTIVE_COMPARATOR

prednisolone

Intervention Type: DRUG

prednisolone (2.7 mg)

Dipyridamole

total daily dose during treatment period (days 14-98) 360 mg dipyridamole administered as 180 mg dipyridamole at 8 AM and and 180 mg dipyridamole at 1 PM titration dose 1 (days 0-6) 90 mg dipyridamole administered 45 mg dipyridamole at 8 AM and 45 mg dipyridamole at 1 PM titration dose 2 (days 7-13) 180 mg dipyridamole administered as 90 mg dipyridamole at 8 AM and 90 mg dipyridamole at 1 PM

Group Type: ACTIVE_COMPARATOR

dipyridamole

Intervention Type: DRUG

dipyridamole 360 mg

Placebo

placebo administered twice per day at 8 AM and 1 PM

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo

Interventions

CRx-102 (2.7/180)

prednisolone 2.7 mg plus dipyridamole 180 mg

Intervention Type: DRUG

prednisolone

prednisolone (2.7 mg)

Intervention Type: DRUG

dipyridamole

dipyridamole 360 mg

Intervention Type: DRUG

placebo

placebo

Intervention Type: DRUG

CRx-102 (2.7/360)

Prednisolone 2.7 mg plus Dipyridamole 360 mg

Intervention Type: DRUG

Other Intervention Names

prednisolone 2.7 mg plus dipyridamole 180 mg; dipyridamole 360 mg; Prednisolone 2.7 mg plus Dipyridamole 360 mg

Eligibility Criteria

Inclusion Criteria

• Subject must voluntarily give written informed consent
• Subject must be ≥ 18 years of age
• Subject must have RA (ACR criteria)
• Subject must have at least 4 swollen joints and at least 6 tender joints at screening and baseline (28 joint count)
• Subject must have a CRP > Upper Limit of Normal at screening
• Subject must have been on DMARD or DMARD combination (e.g. MTX + hydroxychloroquine) for at least 3 months and be on a stable dose of DMARD(s) for at least 6 weeks prior to screening.
• For MTX subjects: MTX ≥ 7.5 mg weekly (po/sc/im) and willing to take folic acid or folinic acid supplementation
• Subject willing to take concomitant multivitamin or the equivalent of 400 I.U. vitamin D and the equivalent of 1000 mg of elemental calcium daily

Exclusion Criteria

• History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease
• Wheelchair or bed bound
• History of osteoporotic fracture
• History of malignancy within the past 10 years. However, subjects with a history of treated or excised basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate
• 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 cosmetic)
• History of drug or alcohol abuse (as defined by the Investigator)
• History of bleeding disorder
• History of gastrointestinal bleeding within 5 years of screening
• History of severe migraines or headaches
• History of glaucoma
• Active diabetic retinopathy
• Visually compromising cataract
• History of opportunistic infection within the previous 12 months
• Active Tuberculosis (TB)
• 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 virus (HCV) antibody
• Positive for HBsAg
• Known positive HIV antibody
• Has a history of hypersensitivity to glucocorticoids and/or dipyridamole
• Treatment with oral, intra-articular, intramuscular, or intravenous glucocorticoids within 6 weeks prior to screening; inhaled glucocorticoid is permitted
• Treatment with any tumor necrosis factor-alpha (TNFα) biologic, anakinra or abatacept within 2 months prior to screening
• Treatment with rituximab
• Treatment with another investigational drug 3 months prior to screening
• Treatment with anticoagulants including: dipyridamole, warfarin, clopidogrel, ticlopidine; Acetylsalicylic acid > 150 mg per day
• Treatment with any concomitant medications that have not been at a stable dose for at least 28 days prior to screening
• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) laboratory values that exceed 1.5 x ULN
• HbA1C value of > 7.0%
• Current enrollment in any other study with investigational drug or device
• Female subject who is pregnant or lactating or of child bearing potential and not using acceptable methods of contraception (birth control pills, barriers or abstinence)
• 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: 18 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

Birmingham, Alabama, United States

Huntsville, Alabama, United States

Phoenix, Arizona, United States

Little Rock, Arkansas, United States

Anaheim, California, United States

La Jolla, California, United States

Westlake Village, California, United States

Palm Harbor, Florida, United States

Elizabethtown, Kentucky, United States

Haddon Heights, New Jersey, United States

Mayfield Village, Ohio, United States

Oklahoma City, Oklahoma, United States

Dallas, Texas, United States

Buenos Aires, Buenos Aires, Argentina

Rosario, Santa Fe Province, Argentina

San Jan, , Argentina

San Miguel de Tucumán, , Argentina

Winnipeg, Manitoba, Canada

St. John's, Newfoundland and Labrador, Canada

Hamilton, Ontario, Canada

Windsor, Ontario, Canada

Tallinn, , Estonia

Tartu, , Estonia

Békéscsaba, , Hungary

Esztergom, , Hungary

Szolnok, , Hungary

Kaunas, , Lithuania

Vilnius, , Lithuania

Aguascalientes, Aguascalientes, Mexico

Vallarta Norte, Guadalajara, Mexico

Bialystok, , Poland

Elblag, , Poland

Katowice, , Poland

Krakow, , Poland

Lublin, , Poland

Poznan, , Poland

Torun, , Poland

Warsaw, , Poland

Bucharest, , Romania

Cluj-Napoca, , Romania

Timișoara, , Romania

Moscow, , Russia

Saint Petersburg, , Russia

Belgrade, , Serbia

Niška Banja, , Serbia

Pretoria, Gauteng, South Africa

Cape Town, Western Cape, South Africa

Worcester, Western Cape, South Africa

Countries

United States; Argentina; Canada; Estonia; Hungary; Lithuania; Mexico; Poland; Romania; Russia; Serbia; South Africa

Other Identifiers

CRx-102-007

Identifier Type: -

Identifier Source: org_study_id