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Study to Assess the Safety and Efficacy of Modified-Release Prednisone (Lodotra®) Therapy in Patients With Active Rheumatoid Arthritis (CAPRA-2)

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ClinicalTrials.gov Identifier: NCT00650078
Recruitment Status : Completed
First Posted : April 1, 2008
Results First Posted : December 13, 2012
Last Update Posted : April 30, 2013
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: MR prednisone
Drug: Placebo
Enrollment 350
Recruitment Details Approximately 350 patients were to be enrolled (at screening, Visit 0), with a minimum of 6 and a maximum of 28 patients at each center. It was planned to randomize (at Visit 1) a total of 294 patients in 50-55 centers in North America and Europe (Germany, Hungary, Poland and UK). First patient enrolled March, 2008; last patient contact May, 2009.
Pre-assignment Details The study consisted of a 1 week screening phase followed by a 12 week double blind treatment phase. In addition to their standard RA medication, patients received placebo during the 1 week screening phase. The purpose of the screening phase was to establish the patient's compliance with study medication and completion of diary entries.
Arm/Group Title NP01 Placebo
Hide Arm/Group Description Modified Release (MR) prednisone 5 mg [Not Specified]
Period Title: Overall Study
Started 231 119
Completed 217 106
Not Completed 14 13
Arm/Group Title NP01 Placebo Total
Hide Arm/Group Description Modified Release (MR) prednisone 5 mg [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 231 119 350
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 231 participants 119 participants 350 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
186
  80.5%
95
  79.8%
281
  80.3%
>=65 years
45
  19.5%
24
  20.2%
69
  19.7%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 231 participants 119 participants 350 participants
57.1  (9.89) 57.5  (9.55) 57.2  (9.76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 231 participants 119 participants 350 participants
Female
192
  83.1%
102
  85.7%
294
  84.0%
Male
39
  16.9%
17
  14.3%
56
  16.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 231 participants 119 participants 350 participants
United States 48 27 75
Hungary 67 35 102
Canada 8 5 13
Poland 98 47 145
Germany 1 2 3
United Kingdom 9 3 12
1.Primary Outcome
Title ACR 20 Response Rate at Visit 4
Hide Description

Responders were defined as patients whose improvement from baseline to Visit 4 (Week 12) fulfilled all 3 of the following criteria:

  • > 20% reduction in the tender joint count (0-28)
  • > 20% reduction in the swollen joint count (0-28)
  • > 20% reduction in 3 out of the 5 following additional measures:

    • Patient’s assessment of pain
    • Patient’s global assessment of disease activity
    • Physician’s global assessment of disease activity
    • Functional Disability Index of the Health Assessment Questionnaire
    • C-reactive protein or erythrocyte sedimentation rate
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified Intention to Treat (mITT) efficacy population included all patients who were randomized and received at least 1 dose of study medication. Patients were analyzed according to the treatment to which they were intended to be randomized. All missing values were imputed as non-responders.
Arm/Group Title NP01 Placebo
Hide Arm/Group Description:
Modified Release (MR) prednisone 5 mg
[Not Specified]
Overall Number of Participants Analyzed 231 119
Measure Type: Number
Unit of Measure: participants
108 34
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NP01, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments The p-value was based on logistic regression with treatment, geographic region, gender, and median age class as factors.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.25
Confidence Interval (2-Sided) 95%
1.39 to 3.64
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Relative Reduction of Morning Stiffness
Hide Description Data for the duration of morning stiffness were obtained from patient diaries. Duration of morning stiffness was the difference between the time of resolution of morning stiffness and the time of wake-up. Duration of morning stiffness is the average of the morning stiffness duration (minutes) over the last 7 days prior to visit day (including day of visit). If more than 4 assessments were missing, then the duration was set to missing. Baseline was the value recorded at Week -1 (Visit 0).
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified Intention to Treat (mITT) efficacy population included all patients who were randomized and received at least 1 dose of study medication. Patients were analyzed according to the treatment to which they were intended to be randomized. Excludes those participants with missing data. Analysis used last observation carried forward imputation.
Arm/Group Title NP01 Placebo
Hide Arm/Group Description:
Modified Release (MR) prednisone 5 mg
[Not Specified]
Overall Number of Participants Analyzed 216 107
Median (95% Confidence Interval)
Unit of Measure: Relative Change from Baseline (%)
-55.22
(-69.7 to -47.9)
-34.62
(-43.0 to -19.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NP01, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments Wilcoxon Rank Sum Test p-value
Method Hodges-Lehman method
Comments The difference between the treatment groups was assessed using the median and the 95% CI of the median computed using the Hodges Lehmann method.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -19.6
Confidence Interval (2-Sided) 95%
-31.7 to -6.1
Estimation Comments [Not Specified]
Time Frame Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title NP01 Placebo
Hide Arm/Group Description Modified Release (MR) prednisone 5 mg [Not Specified]
All-Cause Mortality
NP01 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
NP01 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/231 (0.43%)      2/119 (1.68%)    
Cardiac disorders     
myocardial ischaemia  1  0/231 (0.00%)  0 1/119 (0.84%)  1
palpitations  1  1/231 (0.43%)  1 0/119 (0.00%)  0
General disorders     
chest discomfort  1  1/231 (0.43%)  1 0/119 (0.00%)  0
Investigations     
cytology abnormal  1  0/231 (0.00%)  0 1/119 (0.84%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
NP01 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   69/231 (29.87%)      49/119 (41.18%)    
Gastrointestinal disorders     
diarrhea  1  4/231 (1.73%)  1/119 (0.84%) 
vomiting  1  3/231 (1.30%)  1/119 (0.84%) 
General disorders     
oedema peripheral  1  2/231 (0.87%)  2/119 (1.68%) 
Infections and infestations     
nasopharyngitis  1  11/231 (4.76%)  4/119 (3.36%) 
bronchitis  1  3/231 (1.30%)  5/119 (4.20%) 
Musculoskeletal and connective tissue disorders     
arthralgia  1  24/231 (10.39%)  24/119 (20.17%) 
rheumatoid arthritis  1 [1]  15/231 (6.49%)  11/119 (9.24%) 
back pain  1  3/231 (1.30%)  1/119 (0.84%) 
Nervous system disorders     
headache  1  9/231 (3.90%)  5/119 (4.20%) 
Renal and urinary disorders     
hematuria  1  1/231 (0.43%)  3/119 (2.52%) 
Skin and subcutaneous tissue disorders     
rash  1  4/231 (1.73%)  1/119 (0.84%) 
Vascular disorders     
hypertension  1  5/231 (2.16%)  1/119 (0.84%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.0)
[1]
Includes rheumatoid arthritis aggravated and rheumatoid arthritis flare-up(MedDRA lowest level term)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first publication shall be the presentation of a joint, multicenter publication of the Study results. If such a multicenter publication is not submitted within 24 months after conclusion of the Study at all sites, INSTITUTION/INVESTIGATOR may publish the results from the INSTITUTION’S site individually, provided that it is submitted to SPONSOR for review and comment 60 days prior to submission for publication.
Results Point of Contact
Name/Title: Senior Vice President, Clinical Development & Operations
Organization: Horizon Pharma
Phone: 224-383-3012
Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland
ClinicalTrials.gov Identifier: NCT00650078     History of Changes
Other Study ID Numbers: NP01-007
EudraCT-Number: 2007-003508-36
First Submitted: March 28, 2008
First Posted: April 1, 2008
Results First Submitted: November 1, 2012
Results First Posted: December 13, 2012
Last Update Posted: April 30, 2013