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

• 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: Horizon Pharma Ireland, Ltd., Dublin Ireland
• Information provided by (Responsible Party): Horizon Pharma Ireland, Ltd., Dublin Ireland

Tracking Information

• First Submitted Date: March 28, 2008
• First Posted Date: April 1, 2008
• Results First Submitted Date: November 1, 2012
• Results First Posted Date: December 13, 2012
• Last Update Posted Date: April 30, 2013
• Study Start Date: March 2008
• Actual Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 15, 2012)

ACR 20 Response Rate at Visit 4 [ Time Frame: Week 12 ]

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

• Original Primary Outcome Measures (submitted: March 31, 2008): ACR 20 response rate [ Time Frame: Week 12 ]

Current Secondary Outcome Measures (submitted: November 15, 2012)

Relative Reduction of Morning Stiffness [ Time Frame: Week 12 ]

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).

• Original Secondary Outcome Measures (submitted: March 31, 2008): Relative reduction of morning stiffness [ Time Frame: Week 12 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Assess the Safety and Efficacy of Modified-Release Prednisone (Lodotra®) Therapy in Patients With Active Rheumatoid Arthritis
• Official Title: A Randomized Multi-Center, Double-Blind, Placebo-Controlled Study of a New Modified-Release Tablet Formulation of Prednisone (Lodotra®) in Patients With Rheumatoid Arthritis
• Brief Summary: The purpose of the study is to compare the safety and efficacy, with regards to the signs and symptoms, of MR prednisone (Lodotra®) versus placebo in combination with standard Disease Modifying Anti-Rheumatic Drug (DMARD) treatment in patients with active rheumatoid arthritis.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis

Intervention

• Drug: MR prednisone
  1 x 5 mg daily
• Drug: Placebo
  1x daily

Study Arms

• Experimental: NP01
  Modified Release (MR) prednisone 5 mg
  Intervention: Drug: MR prednisone
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Publications *

• Alten R, Grahn A, Holt RJ, Rice P, Buttgereit F. Delayed-release prednisone improves fatigue and health-related quality of life: findings from the CAPRA-2 double-blind randomised study in rheumatoid arthritis. RMD Open. 2015 Aug 13;1(1):e000134. doi: 10.1136/rmdopen-2015-000134. eCollection 2015.
• Buttgereit F, Mehta D, Kirwan J, Szechinski J, Boers M, Alten RE, Supronik J, Szombati I, Romer U, Witte S, Saag KG. Low-dose prednisone chronotherapy for rheumatoid arthritis: a randomised clinical trial (CAPRA-2). Ann Rheum Dis. 2013 Feb;72(2):204-10. doi: 10.1136/annrheumdis-2011-201067. Epub 2012 May 5.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 20, 2012): 350
• Original Estimated Enrollment (submitted: March 31, 2008): 294
• Actual Study Completion Date: May 2009
• Actual Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Documented history of RA in agreement with ACR criteria
• DMARD treatment for RA greater than or equal to 6 months, with a stable dose greater than or equal to 6 weeks prior to screening visit
• Duration of morning stiffness greater than or equal to 45 minutes
• greater than or equal to 4 swollen joints (out of 28)
• greater than or equal to 4 tender joints (out of 28)

Exclusion Criteria:

• Suffering from another disease, which requires glucocorticoid treatment during the study period
• Synovectomy within 4 months prior to study start

• Use of glucocorticoids:

  • Continued use of systemic glucocorticoids within 4 weeks prior to screening visit
  • Intermittent use of glucocorticoids within 2 weeks prior to screening visit.
  • Joint injections within 6 weeks prior to screening visit
  • Topical glucocorticoids must be stopped at screening visit
• Use of biologicals such as: tumor necrosis factor α (TNFα) inhibitors and other compounds within 5 serum half lives prior to screening visit
• Pregnancy or nursing

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Germany, Hungary, Poland, United Kingdom, United States

Administrative Information

• NCT Number: NCT00650078
• Other Study ID Numbers: NP01-007; EudraCT-Number: 2007-003508-36
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland
• Original Responsible Party: Chief Medical Officer, Nitec Pharma GmbH
• Current Study Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Frank Buttgereit, Prof. Dr.; Charité Campus Mitte, Germany

• PRS Account: Horizon Pharma Ireland, Ltd., Dublin Ireland
• Verification Date: April 2013