Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Multicenter Study to Evaluate CRx-102 vs. Each of Its Components to Treat Active Rheumatoid Arthritis (MARS-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00551707
Recruitment Status : Completed
First Posted : October 31, 2007
Results First Posted : April 29, 2014
Last Update Posted : April 29, 2014
Sponsor:
Information provided by (Responsible Party):
Zalicus

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.


Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: CRx-102 (2.7/180) Drug: prednisolone Drug: dipyridamole Drug: placebo Drug: CRx-102 (2.7/360) Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Superiority of CRx-102 Over Each of Its Components When Given to Subjects With Active Rheumatoid Arthritis (RA)
Study Start Date : October 2007
Actual Primary Completion Date : November 2008
Actual Study Completion Date : January 2009

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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
Drug: CRx-102 (2.7/180)
prednisolone 2.7 mg plus dipyridamole 180 mg
Other Name: prednisolone 2.7 mg plus dipyridamole 180 mg

Experimental: 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
Drug: CRx-102 (2.7/180)
prednisolone 2.7 mg plus dipyridamole 180 mg
Other Name: prednisolone 2.7 mg plus dipyridamole 180 mg

Drug: CRx-102 (2.7/360)
Prednisolone 2.7 mg plus Dipyridamole 360 mg
Other Name: Prednisolone 2.7 mg plus Dipyridamole 360 mg

Active Comparator: 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
Drug: prednisolone
prednisolone (2.7 mg)

Active Comparator: 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
Drug: dipyridamole
dipyridamole 360 mg
Other Name: dipyridamole 360 mg

Placebo Comparator: Placebo
placebo administered twice per day at 8 AM and 1 PM
Drug: placebo
placebo




Primary Outcome Measures :
  1. Absolute C-reactive Protein (CRP) Values at Day 98 - As Treated Population [ Time Frame: Day 98 ]
    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 CRP values in the As-Treated population were calculated.


Secondary Outcome Measures :
  1. Percent Change From Baseline to Day 98 in C-reactive Protein (CRP) Values - As Treated Population [ Time Frame: baseline to day 98 ]
    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 CRP values in the As-Treated population were calculated.

  2. To Assess the Superiority of CRx-102 Compared to Prednisolone and Dipyridamole Using American College of Rheumatology Rating Scale (20% or More Improvement; ACR20) Calculated From Baseline to Day 98 in Subjects With Active Rheumatoid Arthritis [ Time Frame: baseline to day 98 ]
    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 CRP values in the As-Treated population were calculated.

  3. To Assess the Efficacy of CRx-102 Compared to Placebo Using ACR 20 Calculated From Baseline to Day 98 [ Time Frame: baseline to 98 Days ]
    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 CRP values in the As-Treated population were calculated.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00551707


  Show 48 Study Locations
Sponsors and Collaborators
Zalicus
Investigators
Layout table for investigator information
Study Director: Margaret Lee, PhD Zalicus

Layout table for additonal information
Responsible Party: Zalicus
ClinicalTrials.gov Identifier: NCT00551707     History of Changes
Other Study ID Numbers: CRx-102-007
First Posted: October 31, 2007    Key Record Dates
Results First Posted: April 29, 2014
Last Update Posted: April 29, 2014
Last Verified: March 2014

Keywords provided by Zalicus:
CombinatoRx
CRx-102
Rheumatoid Arthritis
Prednisolone
Dipyridamole
ACR20

Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Dipyridamole
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Phosphodiesterase Inhibitors