CompletedNCT00551707MARS-1Updated Apr 29, 2014Results posted

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

A Phase 2 interventional study of CRx-102 (2.7/180) and prednisolone in Rheumatoid Arthritis, sponsored by Zalicus. Completed at 48 sites in 12 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-04-29.

Sponsored by Zalicus · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 51
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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.

Read the 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 studied

Rheumatoid Arthritis

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Keywords

CombinatoRx
CRx-102
Rheumatoid Arthritis
Prednisolone
Dipyridamole
ACR20

In context

Arthritis

3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.

This study's enrollment of 51 is below the median of 90 across 2,377 interventional studies indexed under Arthritis.

Browse Arthritis studies →

Lead sponsor

Zalicus is the lead sponsor of 12 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Investigator, Outcomes assessor)
Enrollment: 51 participants (actual)

Study arms

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)
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) · Drug: CRx-102 (2.7/360)
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
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
Placebo comparator
Placebo
placebo administered twice per day at 8 AM and 1 PM
Drug: placebo

Interventions

DrugCRx-102 (2.7/180)
prednisolone 2.7 mg plus dipyridamole 180 mg
Also known as: prednisolone 2.7 mg plus dipyridamole 180 mg
Drugprednisolone
prednisolone (2.7 mg)
Drugdipyridamole
dipyridamole 360 mg
Also known as: dipyridamole 360 mg
Drugplacebo
placebo
DrugCRx-102 (2.7/360)
Prednisolone 2.7 mg plus Dipyridamole 360 mg
Also known as: Prednisolone 2.7 mg plus Dipyridamole 360 mg

What researchers measure

Primary outcomes

Absolute C-reactive Protein (CRP) Values at Day 98 - As Treated Population
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.
Time frame: Day 98

Secondary outcomes

Percent Change From Baseline to Day 98 in C-reactive Protein (CRP) Values - As Treated Population
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.
Time frame: baseline to day 98
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
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.
Time frame: baseline to day 98
To Assess the Efficacy of CRx-102 Compared to Placebo Using ACR 20 Calculated From 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.
Time frame: baseline to 98 Days

Results

Posted Apr 29, 2014

Participant flow

Participant flow — Overall Study
Milestone	CRx-102 (2.7/180)	CRx-102 (2.7/360)	Prednisolone	Dipyridamole	Placebo
Started	4	22	13	8	4
Completed	4	16	10	4	3
Not completed	0	6	3	4	1

Outcome measures

SecondaryPercent Change From Baseline to Day 98 in C-reactive Protein (CRP) Values - As Treated Population

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.

Time frame:: baseline to day 98
Reported as:: Median · percentage of change from baseline

Percent Change From Baseline to Day 98 in C-reactive Protein (CRP) Values - As Treated Population
percentage of change from baseline	CRx-102 (2.7/180)	CRx-102 (2.7/360)	Prednisolone	Dipyridamole	Placebo
Percent Change From Baseline to Day 98 in C-reactive Protein (CRP) Values - As Treated Population	-29.90 ± 18.45	-40.84 ± 66.80	15.92 ± 1453.54	-33.67 ± 30.43	-27.64 (-35.0 to 203.3)

SecondaryTo 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

Results for this outcome have not been posted.

PrimaryAbsolute C-reactive Protein (CRP) Values at Day 98 - As Treated Population

Time frame:: Day 98
Reported as:: Median · mg/L

Absolute C-reactive Protein (CRP) Values at Day 98 - As Treated Population
mg/L	CRx-102 (2.7/180)	CRx-102 (2.7/360)	Prednisolone	Dipyridamole	Placebo
Absolute C-reactive Protein (CRP) Values at Day 98 - As Treated Population	12.85 ± 5.39	14.25 ± 15.52	21.85 ± 27.10	16.60 ± 16.22	2.68 ± 4.88

SecondaryTo Assess the Efficacy of CRx-102 Compared to Placebo Using ACR 20 Calculated From Baseline to Day 98

Time frame:: baseline to 98 Days

Results for this outcome have not been posted.

Adverse events

Collected over From subject entry into the study (defined as the time at which the informed consent form was signed) to the end of study visit at day 98. Non-serious events are listed at a 4% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
CRx-102 (Dose 1)	—	0/4 (0%)	0/4 (0%)
CRx-102 (Dose 2)	—	0/22 (0%)	10/22 (45.5%)
Prednisolone	—	0/13 (0%)	2/13 (15.4%)
Dipyridamole	—	0/8 (0%)	4/8 (50%)
Placebo	—	0/4 (0%)	2/4 (50%)

Most frequent other events

Most frequent other events
Event	CRx-102 (Dose 1)	CRx-102 (Dose 2)	Prednisolone	Dipyridamole	Placebo
HeadacheNervous system disorders	0/4	6/22	1/13	2/8	2/4
NauseaGastrointestinal disorders	0/4	0/22	0/13	2/8	1/4
DyspepsiaGastrointestinal disorders	0/4	1/22	0/13	0/8	1/4
Oedema PeripheralGeneral disorders	0/4	2/22	0/13	0/8	0/4
Upper respiratory tract infectionInfections and infestations	0/4	1/22	1/13	0/8	0/4

Baseline characteristics

Age, Continuous
Age, Continuous(years)	CRx-102 (2.7/180)	CRx-102 (2.7/360)	Prednisolone	Dipyridamole	Placebo	Total
Mean	51.8 ± 5.50	56.2 ± 11.96	55.8 ± 11.32	56.5 ± 12.76	58.8 ± 9.54	56.0 ± 11.09

Sex: Female, Male
Sex: Female, Male(Participants)	CRx-102 (2.7/180)	CRx-102 (2.7/360)	Prednisolone	Dipyridamole	Placebo	Total
Female	2	18	5	7	3	35
Male	2	4	8	1	1	16

Study locations

48 sites

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
Rosario, Santa Fe, Argentina
Buenos Aires, Argentina
San Jan, Argentina
San Miguel de Tucuman, Argentina
Winnipeg, Manitoba, Canada
St. John's, Newfoundland and Labrador, Canada
Hamilton, Ontario, Canada
Windsor, Ontario, Canada
Tallinn, Estonia
Tartu, Estonia
Bekescsaba, Hungary
Esztergom, Hungary
Szolnok, Hungary
Kaunas, Lithuania
Vilnius, Lithuania
Aguas Calientes, Aguascalientes, Mexico
Vallarta Norte, Guadalajara, Mexico
Bialystok, Poland
Elblag, Poland
Katowice, Poland
Krakow, Poland
Lublin, Poland
Poznan, Poland
Torun, Poland
Warszawa, Poland
Bucuresti, Romania
Cluj Napoca, Romania
Timisoara, Romania
Moscow, Russian Federation
St. Petersburg, Russian Federation
Belgrade, Serbia
Niska Banja, Serbia
Pretoria, Gauteng, South Africa
Cape Town, Western Cape, South Africa
Worcester, Western Cape, South Africa

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 29, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00551707
Lead sponsor: Zalicus
Responsible party: Sponsor
First posted: Oct 31, 2007
Start date: Oct 2007
Primary completion: Nov 2008
Completion: Jan 2009
Results posted: Apr 29, 2014
Last update: Apr 29, 2014

Study contacts

Margaret Lee, PhD

study director · Zalicus

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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