NCT00146640

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

Completed Phase 3 Results posted Last updated 3 July 2018

What this trial tests

Phase 3 trial testing MR Prednisone in Rheumatoid Arthritis in 288 participants. Completed in 31 January 2007.

Timeline

31 August 2004

Primary endpoint
31 January 2007

31 January 2007

Quick facts

Lead sponsor	Merck KGaA, Darmstadt, Germany
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	288
Start date	31 August 2004
Primary completion	31 January 2007
Estimated completion	31 January 2007
Sites	24 locations across Germany, Poland

Drugs / interventions tested

• MR Prednisone — full drug profile →
• IR Prednisone — full drug profile →
• Placebo - MR Prednisone — full drug profile →
• Placebo - IR Prednisone — full drug profile →

Conditions studied

• Rheumatoid Arthritis — all drugs for Rheumatoid Arthritis →

Sponsor

Merck KGaA, Darmstadt, Germany — full company profile →

Who can join

Adults 18 to 80, any sex, with Rheumatoid Arthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Relative Change From Baseline in Duration of Morning Stiffness at Week 12 Primary · Baseline, 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.

Group	Value	95% CI
MR Prednisone	-22.7	± 89.1
IR Prednisone	-0.4	± 89.0

Relative Change From Baseline in 28-Joint Disease Activity Score (DAS28) at Week 12 Secondary · Baseline, 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

Group	Value	95% CI
MR Prednisone	-9.03	-11.9 – -6.2
IR Prednisone	-12.30	-15.2 – -9.4

Percentage of Participants With Recurrence of Joint Stiffness at Week 12 Secondary · 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.

Group	Value	95% CI
MR Prednisone	47
IR Prednisone	43

Relative Change From Baseline in Pain Intensity at Week 12 Secondary · Baseline, 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.

Group	Value	95% CI
MR Prednisone	-8.57	-17.7 – 0.6
IR Prednisone	-6.53	-20.4 – 7.3

Relative Change From Baseline in Quality of Sleep at Week 12 Secondary · Baseline, 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.

Group	Value	95% CI
MR Prednisone	4.63	-9.9 – 19.1
IR Prednisone	0.13	-12.3 – 12.5

Relative Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 Secondary · Baseline, 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 \[valu

Group	Value	95% CI
MR Prednisone	0.07	-6.6 – 6.7
IR Prednisone	-4.7	-9.6 – 0.1

Relative Change From Baseline in Short-Form 36 (SF36) Mental Component Score (MCS) at Week 12 Secondary · Baseline, 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 val

Group	Value	95% CI
MR Prednisone	10.63	0.8 – 20.5
IR Prednisone	18.08	9.7 – 26.4

Relative Change From Baseline in SF36 Physical Component Score (PCS) at Week 12 Secondary · Baseline, 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

Group	Value	95% CI
MR Prednisone	19.43	7.77 – 31.1
IR Prednisone	21.0	11.05 – 30.9

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MR Prednisone

Serious: 4/144 (3%)

Deaths: —

IR Prednisone

Serious: 3/144 (2%)

Deaths: —

Serious adverse events (1 terms)

Reaction	System	MR Prednisone	IR Prednisone
	General disorders	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	MR Prednisone	IR Prednisone
Rheumatoid arthritis	Immune system disorders	—	—
Nasopharyngitis	Respiratory, thoracic and mediastinal disorders	—	—
Abdominal pain (upper)	Gastrointestinal disorders	—	—

Most-reported serious reactions: .

Data from ClinicalTrials.gov NCT00146640 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial.
   Buttgereit F, Doering G, Schaeffler A, Witte S, et al · · 2008 · cited 225× · PMID 18207016 · DOI 10.1016/s0140-6736(08)60132-4
2. Hypothalamus-pituitary-adrenal axis function in patients with rheumatoid arthritis treated with nighttime-release prednisone.
   Alten R, Döring G, Cutolo M, Gromnica-Ihle E, et al · · 2010 · cited 51× · PMID 20682671 · DOI 10.3899/jrheum.100051
3. Morning stiffness response with delayed-release prednisone after ineffective course of immediate-release prednisone.
   Alten R, Holt R, Grahn A, Rice P, et al · · 2015 · cited 11× · PMID 26114379 · DOI 10.3109/03009742.2015.1038582