Trial Outcomes & Findings for A Study Comparing CRx-102 Plus Disease-modifying Anti-rheumatic Drug (DMARD) Therapy to Placebo Plus DMARD Therapy in RA (NCT NCT00747214)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

59 participants

Primary outcome timeframe

Baseline and Day 42

Results posted on

2014-05-20

Participant Flow

Participant milestones

Participant milestones
Measure	CRx-102 Plus DMARD Therapy Daily oral treatment with CRx-102, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy The following dose escalation scheme was used: Days 1 to 7 Dose level 1: CRx-102 (200 mg dipyridamole + 3 mg prednisolone) Days 8 to 42 Dose level 2: CRx-102 (400 mg dipyridamole + 3 mg prednisolone)	Placebo Plus DMARD Therapy Daily oral treatment with placebo, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy
Overall Study STARTED	27	32
Overall Study COMPLETED	19	29
Overall Study NOT COMPLETED	8	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CRx-102 Plus DMARD Therapy n=19 Participants Daily oral treatment with CRx-102, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy The following dose escalation scheme was used: Days 1 to 7 Dose level 1: CRx-102 (200 mg dipyridamole + 3 mg prednisolone) Days 8 to 42 Dose level 2: CRx-102 (400 mg dipyridamole + 3 mg prednisolone)	Placebo Plus DMARD Therapy n=27 Participants Daily oral treatment with placebo, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy	Total n=46 Participants Total of all reporting groups
Age, Continuous	56.5 years STANDARD_DEVIATION 6.53 • n=5 Participants	60.0 years STANDARD_DEVIATION 12.25 • n=7 Participants	58.5 years STANDARD_DEVIATION 10.34 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	21 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 42

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.

Outcome measures

Outcome measures
Measure	CRx-102 Plus DMARD Therapy n=19 Participants Daily oral treatment with CRx-102, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy The following dose escalation scheme was used: Days 1 to 7 Dose level 1: CRx-102 (200 mg dipyridamole + 3 mg prednisolone) Days 8 to 42 Dose level 2: CRx-102 (400 mg dipyridamole + 3 mg prednisolone)	Placebo Plus DMARD Therapy n=27 Participants Daily oral treatment with placebo, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy
Change in CRP From Baseline to Day 42	-16.12 percentage change from baseline Standard Deviation 94.99	9.60 percentage change from baseline Standard Deviation 74.15

SECONDARY outcome

Timeframe: Day 42

The percentage of subjects in each group that achieved an ACR 20 response on Day 42

Outcome measures

Outcome measures
Measure	CRx-102 Plus DMARD Therapy n=19 Participants Daily oral treatment with CRx-102, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy The following dose escalation scheme was used: Days 1 to 7 Dose level 1: CRx-102 (200 mg dipyridamole + 3 mg prednisolone) Days 8 to 42 Dose level 2: CRx-102 (400 mg dipyridamole + 3 mg prednisolone)	Placebo Plus DMARD Therapy n=27 Participants Daily oral treatment with placebo, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy
Improvement of ACR 20 Scores at End of Study (Day 42/Visit 5)	63 percentage of participants	30 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Day 42

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.

Outcome measures

Outcome measures
Measure	CRx-102 Plus DMARD Therapy n=19 Participants Daily oral treatment with CRx-102, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy The following dose escalation scheme was used: Days 1 to 7 Dose level 1: CRx-102 (200 mg dipyridamole + 3 mg prednisolone) Days 8 to 42 Dose level 2: CRx-102 (400 mg dipyridamole + 3 mg prednisolone)	Placebo Plus DMARD Therapy n=27 Participants Daily oral treatment with placebo, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy
Change in DAS28 Score From Baseline to Day 42	-1.521 units on a scale Standard Deviation 1.574	-0.697 units on a scale Standard Deviation 1.435

SECONDARY outcome

Timeframe: Baseline and Day 42

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.

Outcome measures

Outcome measures
Measure	CRx-102 Plus DMARD Therapy n=19 Participants Daily oral treatment with CRx-102, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy The following dose escalation scheme was used: Days 1 to 7 Dose level 1: CRx-102 (200 mg dipyridamole + 3 mg prednisolone) Days 8 to 42 Dose level 2: CRx-102 (400 mg dipyridamole + 3 mg prednisolone)	Placebo Plus DMARD Therapy n=27 Participants Daily oral treatment with placebo, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy
Change in Fatigue (MAF Scale) Score From Baseline to Day 42	-7.840 units on a scale Standard Deviation 10.605	-2.965 units on a scale Standard Deviation 9.186

Adverse Events

CRx-102 Plus DMARD Therapy

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo Plus DMARD Therapy

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CRx-102 Plus DMARD Therapy n=27 participants at risk Daily oral treatment with CRx-102, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy The following dose escalation scheme was used: Days 1 to 7 Dose level 1: CRx-102 (200 mg dipyridamole + 3 mg prednisolone) or placebo equivalent Days 8 to 42 Dose level 2: CRx-102 (400 mg dipyridamole + 3 mg prednisolone) or placebo equivalent	Placebo Plus DMARD Therapy n=32 participants at risk Daily oral treatment with placebo, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy
Gastrointestinal disorders femoral hernia	0.00% 0/27 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.	3.1% 1/32 • Number of events 1 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.

Other adverse events

Other adverse events
Measure	CRx-102 Plus DMARD Therapy n=27 participants at risk Daily oral treatment with CRx-102, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy The following dose escalation scheme was used: Days 1 to 7 Dose level 1: CRx-102 (200 mg dipyridamole + 3 mg prednisolone) or placebo equivalent Days 8 to 42 Dose level 2: CRx-102 (400 mg dipyridamole + 3 mg prednisolone) or placebo equivalent	Placebo Plus DMARD Therapy n=32 participants at risk Daily oral treatment with placebo, dosed twice per day (8AM and 1 PM) plus stable dose of DMARD therapy
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	3.7% 1/27 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.	15.6% 5/32 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.
Nervous system disorders Dizziness	11.1% 3/27 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.	3.1% 1/32 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.
Gastrointestinal disorders Diarrhea	11.1% 3/27 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.	3.1% 1/32 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/27 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.	9.4% 3/32 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.
Nervous system disorders Headache	48.1% 13/27 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.	0.00% 0/32 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.
Gastrointestinal disorders Nausea	25.9% 7/27 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.	6.2% 2/32 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.
Gastrointestinal disorders Vomiting	22.2% 6/27 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.	3.1% 1/32 • 8 weeks: from screening (visit 1) up to 14 days prior to baseline (visit 2) through end of study (visit 5) on day 42.

Additional Information

Margaret Lee, PhD

Zalicus

Phone: 617-301-7142

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60