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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00146640

Enrollment

288

Registered

2005-09-07

Start date

2004-08-31

Completion date

2007-01-31

Last updated

2018-07-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Keywords

active disease, morning stiffness of joints, nighttime application of prednisone, modified release prednisone

Brief 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.

Interventions

DRUGMR Prednisone

Participants will receive tablets containing MR prednisone (to achieve the appropriate dose of 3-10 milligrams \[mg\] prednisone per day) at bed time.

DRUGIR Prednisone

Participants will receive tablets containing IR prednisone (to achieve the appropriate dose of 3-10 mg prednisone per day) in the morning.

DRUGPlacebo - MR Prednisone

Participants will receive placebo matching to MR prednisone tablet at bed time.

DRUGPlacebo - IR Prednisone

Participants will receive placebo matching to IR prednisone tablet in the morning.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Relative Change From Baseline in Duration of Morning Stiffness at Week 12	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.

Secondary

Measure	Time frame	Description
Percentage of Participants With Recurrence of Joint Stiffness at Week 12	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.
Relative Change From Baseline in Pain Intensity at Week 12	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.
Relative Change From Baseline in Quality of Sleep at Week 12	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.
Relative Change From Baseline in 28-Joint Disease Activity Score (DAS28) at Week 12	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 \>5.1 = severe disease activity. Relative (percent) change = (\[value at Week 12 minus value at Baseline\] divided by \[value at baseline\]) multiplied by 100.
Relative Change From Baseline in Short-Form 36 (SF36) Mental Component Score (MCS) at Week 12	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 = (\[value at Week 12 minus value at Baseline\] divided by \[value at baseline\]) multiplied by 100.
Relative Change From Baseline in SF36 Physical Component Score (PCS) at Week 12	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 = (\[value at Week 12 minus value at Baseline\] divided by \[value at baseline\]) multiplied by 100.
Relative Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12	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 \[value at baseline\]) multiplied by 100.

Countries

Germany, Poland

Participant flow

Participants by arm

Arm	Count
MR Prednisone Participants received tablets containing MR prednisone (to achieve the appropriate dose of 3-10 mg prednisone per day) at bed time and placebo matching to IR prednisone tablet in the morning. Total duration of double blind treatment was 12 weeks.	144
IR Prednisone Participants received tablets containing IR prednisone (to achieve the appropriate dose of 3-10 mg prednisone per day) in the morning and placebo matching to MR prednisone tablet at bed time. Total duration of double blind treatment was 12 weeks.	144
Total	288

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	12	10
Overall Study	Medical Reasons	3	0
Overall Study	Non-Medical Reasons	8	4

Baseline characteristics

Characteristic	MR Prednisone	IR Prednisone	Total
Age, Continuous	54.6 years STANDARD_DEVIATION 11.2	55.4 years STANDARD_DEVIATION 11.4	55.0 years STANDARD_DEVIATION 11.3
Sex: Female, Male Female	125 Participants	122 Participants	247 Participants
Sex: Female, Male Male	19 Participants	22 Participants	41 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	20 / 144	29 / 144
serious Total, serious adverse events	4 / 144	3 / 144

Outcome results

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.

Time frame: Baseline, Week 12