A Study Comparing CRx-102 Plus Disease-modifying Anti-rheumatic Drug (DMARD) Therapy to Placebo Plus DMARD Therapy in RA

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Zalicus
ClinicalTrials.gov Identifier:
NCT00747214
First received: September 3, 2008
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

This study was a Multicenter, Randomized, Blinded Study Comparing the Effect of CRx-102 Plus DMARD Therapy to that of Placebo Plus DMARD Therapy on Serum C Reactive Protein (CRP) and Cytokines in Subjects with Rheumatoid Arthritis. This Phase II, 6-week blinded study was planned for 60 subjects with moderate to severe rheumatoid arthritis (RA).


Condition Intervention Phase
Rheumatoid Arthritis
Drug: CRx-102
Drug: Placebo
Drug: DMARD Therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Blinded Study Comparing the Effect of CRx-102 Plus DMARD Therapy to That of Placebo Plus DMARD Therapy on Serum C Reactive Protein (CRP) and Cytokines in Subjects With RA

Resource links provided by NLM:


Further study details as provided by Zalicus:

Primary Outcome Measures:
  • Change in CRP From Baseline to Day 42 [ Time Frame: Baseline and Day 42 ] [ Designated as safety issue: No ]
    The primary efficacy variable in this study was the change in CRP from Baseline (Day 1/Visit 2) to End of Study (Day 42/Visit 5). Blood samples for the analysis of serum CRP were taken at each visit.


Secondary Outcome Measures:
  • Improvement of ACR 20 Scores at End of Study (Day 42/Visit 5) [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    The percentage of subjects in each group that achieved an ACR 20 response on Day 42

  • Change in DAS28 Score From Baseline to Day 42 [ Time Frame: Baseline and Day 42 ] [ Designated as safety issue: No ]
    To calculate the DAS28, the number of swollen joints and tender joints should be assessed using 28-joint counts, the ESR should have been measured in mm/hour, and the patient's general health (GH) or global disease activity measured on a Visual Analog Scale (VAS) of 100 mm must be obtained. Using these data, the DAS28 could be calculated using the following formula: DAS28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.70 * ln(ESR) + 0.014 * GH. The DAS28 provides a number between 0 and 10 that indicates the current activity of RA in the subject. A DAS28 above 5.1 means high disease activity and below 3.2 indicates low activity. Remission is achieved when a DAS28 score is lower than 2.6. The DAS28 measurements were to be taken at each visit.

  • Change in Fatigue (MAF Scale) Score From Baseline to Day 42 [ Time Frame: Baseline and Day 42 ] [ Designated as safety issue: No ]

    The Multidimensional Assessment of Fatigue (MAF) scale is a self-administered, 16 item questionnaire to measure self-reported fatigue (http://www.son.washington.edu/research/maf/). The following steps were used to calculate a single score ranging from 1 (no fatigue) to 50 (severe fatigue).

    1. Convert item #15 to a 0 to 10 scale by multiplying each score by 2.5
    2. Sum items #1, 2, and 3
    3. Average items #4 through 14
    4. Add results from above Steps 1 through 3 to obtain a single score

    A score was not be assigned to items #4 through 14 if a respondent indicated they "did not engage any activity for reasons other than fatigue." If respondent selected "no fatigue" on item #1, a 0 was to be assigned to items #2 through 16; item #16 was not included in the global fatigue index.



Enrollment: 59
Study Start Date: November 2004
Study Completion Date: November 2006
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CRx-102 plus DMARD therapy Drug: CRx-102
Other Name: Prednisolone plus dipyridamole
Drug: DMARD Therapy
DMARD therapy can include methotrexate or other DMARD therapy
Other Name: Disease modifying anti-rheumatic drug therapy
Placebo Comparator: Placebo plus DMARD therapy Drug: Placebo
Other Name: sugar pill
Drug: DMARD Therapy
DMARD therapy can include methotrexate or other DMARD therapy
Other Name: Disease modifying anti-rheumatic drug therapy

Detailed Description:

The primary objective of this study was to:

• Compare the response of CRx-102 plus DMARD therapy to placebo plus DMARD therapy in lowering CRP levels in rheumatoid arthritis subjects.

The secondary objectives of this study were to:

  • Evaluate the changes in inflammatory cytokines in subjects treated with CRx-102 plus DMARD therapy to placebo plus DMARD therapy.
  • Evaluate the efficacy of CRx-102 plus DMARD therapy to placebo plus DMARD therapy using ACR-20 and DAS28 indices as well as fatigue scales.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Was 18 years of age of older
  • Had moderate to severe RA
  • Had at least 3 swollen joints (maximum 28) and 3 tender joints (maximum 28)
  • Had a Baseline CRP level of at least 2.2 mg/L and a DAS28 score >4.5
  • Had been on DMARD therapy for at least 3 months and have been on a stable dose of DMARD therapy for at least 28 days prior to enrollment
  • Had a negative pregnancy test (females)
  • Was not taking glucocorticoids at screening

Exclusion Criteria:

  • Female subject is pregnant or lactating or of child bearing potential not using acceptable methods of birth control (barriers or abstinence). Female subjects using hormonal birth control are not to be enrolled.
  • Subject is currently taking any steroids (glucocorticoids). All glucocorticoids must be discontinued for at least one month prior to entering study. Intraarticular, intramuscular, or intravenous glucocorticoids must not have been given at least 6 weeks prior to entering the study.
  • Subject is currently taking more than 81 mg of aspirin daily.
  • Subject is currently taking a statin, unless she/he has been on a stable dose of the same statin for at least 3 months prior to entering into the trial.
  • Subject has any active infections or recent surgical procedures within 30 days of study initiation.
  • Subject has uncontrolled diabetes mellitus as defined by a HbA1C value ≥ 7.0%.
  • Subject knowingly has HIV or Hepatitis.
  • Subject has undergone administration of any investigational drug within 30 days of study initiation.
  • Subject has a history of hypersensitivity to steroids and/or dipyridamole.
  • Subject has limited mental capacity or language skills such that simple instructions cannot be followed or information regarding adverse events cannot be provided.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00747214

Sponsors and Collaborators
Zalicus
Investigators
Study Director: Margaret Lee, PhD Zalicus
  More Information

No publications provided

Responsible Party: Zalicus
ClinicalTrials.gov Identifier: NCT00747214     History of Changes
Other Study ID Numbers: CRx-102-002
Study First Received: September 3, 2008
Results First Received: January 16, 2014
Last Updated: April 22, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Estonia: The State Agency of Medicine

Keywords provided by Zalicus:
Rheumatoid Arthritis
RA
DMARD
CRP

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antirheumatic Agents
Dipyridamole
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Hematologic Agents
Vasodilator Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 01, 2014