Prednisone Timed-Release Tablet (TRT) Study: Modified-Release (MR) Formulation of Prednisone Compared to Standard Immediate-Release (IR) Prednisone in Participants With Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

A New Timed-Release Tablet Formulation of Prednisone Compared to Standard Prednisone in Patients With Rheumatoid Arthritis- A Randomized, Multi-Centre, Double-Blind, Active Controlled Study With Open Extension on the New Drug Only

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00146640
• Other study ID #: EMR 62215-003
• Status: Completed
• Phase: Phase 3
• Start date: August 31, 2004
• Est. completion date: January 31, 2007

Study information

• Verified date: June 2018
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to investigate if low doses of prednisone MR formulation, given at night and, with active drug release at 2 am, are more effective in controlling joint stiffness, and other disease symptoms of rheumatoid arthritis than standard IR prednisone given in the morning.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 288
• Est. completion date: January 31, 2007
• Est. primary completion date: January 31, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Active disease (inflammatory signs, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP])

• Stable condition

• Stable basic treatments

• Morning stiffness on previous treatment with standard prednisone (below or equal to 10 mg per day) greater than or equal to (>/=) 45 minutes

Exclusion Criteria:

• All contra-indications for glucocorticoids

• Pregnancy

• Concomitant treatment with biologics

• Intra-articular injections or synovectomy within the previous 4 months

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• MR Prednisone
Participants will receive tablets containing MR prednisone (to achieve the appropriate dose of 3-10 milligrams [mg] prednisone per day) at bed time.
• IR Prednisone
Participants will receive tablets containing IR prednisone (to achieve the appropriate dose of 3-10 mg prednisone per day) in the morning.
• Placebo - MR Prednisone
Participants will receive placebo matching to MR prednisone tablet at bed time.
• Placebo - IR Prednisone
Participants will receive placebo matching to IR prednisone tablet in the morning.

Locations

Country	Name	City	State
Germany	Research Site	Aachen
Germany	Research Site	Bad Kreuznach
Germany	Research Site	Berlin
Germany	Research Site	Dresden
Germany	Research Site	Düsseldorf
Germany	Research Site	Erlangen
Germany	Research Site	Frankfurt/Main
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Jena
Germany	Research Site	Köln
Germany	Research Site	Leipzig
Germany	Research Site	München
Germany	Research Site	Ratingen
Germany	Research Site	Rostock
Poland	Research Site	Bialystok
Poland	Research Site	Katowice
Poland	Research Site	Kraków
Poland	Research Site	Lublin
Poland	Research Site	Poznan
Poland	Research Site	Sopot
Poland	Research Site	Torun
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

Germany,  Poland, 

References & Publications (2)

Alten R, Döring G, Cutolo M, Gromnica-Ihle E, Witte S, Straub R, Buttgereit F. Hypothalamus-pituitary-adrenal axis function in patients with rheumatoid arthritis treated with nighttime-release prednisone. J Rheumatol. 2010 Oct;37(10):2025-31. doi: 10.3899 — View Citation

Buttgereit F, Doering G, Schaeffler A, Witte S, Sierakowski S, Gromnica-Ihle E, Jeka S, Krueger K, Szechinski J, Alten R. Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative Change From Baseline in Duration of Morning Stiffness at Week 12	Duration of morning stiffness was defined as the time elapsed (in minutes) between the time of usual awakening (even if not in the morning) and the time the participant was able to resume normal activities without stiffness. Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100.	Baseline, Week 12
Secondary	Relative Change From Baseline in 28-Joint Disease Activity Score (DAS28) at Week 12	DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total DAS28 score range from 0 to approximately 10. DAS28 less than or equal to (=) 3.2 = low disease activity, DAS28 greater than (>) 3.2 to 5.1 = moderate to high disease activity, and DAS28 >5.1 = severe disease activity. Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100.	Baseline, Week 12
Secondary	Percentage of Participants With Recurrence of Joint Stiffness at Week 12	Participants recorded the status of recurrence of joint stiffness (Yes/No) in diary data. Percentage of participants who selected Yes for recurrence of joint stiffness, are reported.	Week 12
Secondary	Relative Change From Baseline in Pain Intensity at Week 12	Participants assessed pain intensity on a 100 millimeter (mm) visual analog scale (VAS), where 0 mm = no pain, 100 mm = worst pain. Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100.	Baseline, Week 12
Secondary	Relative Change From Baseline in Quality of Sleep at Week 12	Participants assessed quality of sleep on a 100 mm VAS, where 0 mm = very good, 100 mm = very bad. Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100.	Baseline, Week 12
Secondary	Relative Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12	HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100.	Baseline, Week 12
Secondary	Relative Change From Baseline in Short-Form 36 (SF36) Mental Component Score (MCS) at Week 12	SF-36 is a standardized survey evaluating 8 domains of functional health and wellbeing: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a domain was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100=highest level of mental functioning). Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100.	Baseline, Week 12
Secondary	Relative Change From Baseline in SF36 Physical Component Score (PCS) at Week 12	SF-36 is a standardized survey evaluating 8 aspects of functional health and wellbeing: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a domain was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100=highest level of physical functioning). Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100.	Baseline, Week 12