Trial Outcomes & Findings for Prednisone Timed-Release Tablet (TRT) Study: Modified-Release (MR) Formulation of Prednisone Compared to Standard Immediate-Release (IR) Prednisone in Participants With Rheumatoid Arthritis (NCT NCT00146640)
NCT ID: NCT00146640
Last Updated: 2018-07-03
Results Overview
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.
COMPLETED
PHASE3
288 participants
Baseline, Week 12
2018-07-03
Participant Flow
Participant milestones
| Measure |
MR Prednisone
Participants received tablets containing modified-release (MR) prednisone (to achieve the appropriate dose of 3-10 milligrams \[mg\] prednisone per day) at bed time and placebo matching to immediate-release (IR) prednisone tablet in the morning. Total duration of double blind treatment was 12 weeks.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
144
|
144
|
|
Overall Study
COMPLETED
|
121
|
130
|
|
Overall Study
NOT COMPLETED
|
23
|
14
|
Reasons for withdrawal
| Measure |
MR Prednisone
Participants received tablets containing modified-release (MR) prednisone (to achieve the appropriate dose of 3-10 milligrams \[mg\] prednisone per day) at bed time and placebo matching to immediate-release (IR) prednisone tablet in the morning. Total duration of double blind treatment was 12 weeks.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
12
|
10
|
|
Overall Study
Medical Reasons
|
3
|
0
|
|
Overall Study
Non-Medical Reasons
|
8
|
4
|
Baseline Characteristics
Prednisone Timed-Release Tablet (TRT) Study: Modified-Release (MR) Formulation of Prednisone Compared to Standard Immediate-Release (IR) Prednisone in Participants With Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
MR Prednisone
n=144 Participants
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.
|
IR Prednisone
n=144 Participants
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.
|
Total
n=288 Participants
Total of all reporting groups
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|---|---|---|---|
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Age, Continuous
|
54.6 years
STANDARD_DEVIATION 11.2 • n=5 Participants
|
55.4 years
STANDARD_DEVIATION 11.4 • n=7 Participants
|
55.0 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
125 Participants
n=5 Participants
|
122 Participants
n=7 Participants
|
247 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: ITT Population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
MR Prednisone
n=125 Participants
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.
|
IR Prednisone
n=129 Participants
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.
|
|---|---|---|
|
Relative Change From Baseline in Duration of Morning Stiffness at Week 12
|
-22.7 percent change
Standard Deviation 89.1
|
-0.4 percent change
Standard Deviation 89.0
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: ITT Population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
MR Prednisone
n=136 Participants
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.
|
IR Prednisone
n=137 Participants
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.
|
|---|---|---|
|
Relative Change From Baseline in 28-Joint Disease Activity Score (DAS28) at Week 12
|
-9.03 percent change
Interval -11.9 to -6.2
|
-12.30 percent change
Interval -15.2 to -9.4
|
SECONDARY outcome
Timeframe: Week 12Population: ITT Population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
MR Prednisone
n=119 Participants
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.
|
IR Prednisone
n=127 Participants
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.
|
|---|---|---|
|
Percentage of Participants With Recurrence of Joint Stiffness at Week 12
|
47 percentage of participants
|
43 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: ITT Population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
MR Prednisone
n=141 Participants
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.
|
IR Prednisone
n=143 Participants
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.
|
|---|---|---|
|
Relative Change From Baseline in Pain Intensity at Week 12
|
-8.57 percent change
Interval -17.7 to 0.6
|
-6.53 percent change
Interval -20.4 to 7.3
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: ITT Population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
MR Prednisone
n=141 Participants
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.
|
IR Prednisone
n=143 Participants
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.
|
|---|---|---|
|
Relative Change From Baseline in Quality of Sleep at Week 12
|
4.63 percent change
Interval -9.9 to 19.1
|
0.13 percent change
Interval -12.3 to 12.5
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: ITT Population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
MR Prednisone
n=137 Participants
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.
|
IR Prednisone
n=138 Participants
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.
|
|---|---|---|
|
Relative Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12
|
0.07 percent change
Interval -6.6 to 6.7
|
-4.7 percent change
Interval -9.6 to 0.1
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: ITT Population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
MR Prednisone
n=114 Participants
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.
|
IR Prednisone
n=117 Participants
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.
|
|---|---|---|
|
Relative Change From Baseline in Short-Form 36 (SF36) Mental Component Score (MCS) at Week 12
|
10.63 percent change
Interval 0.8 to 20.5
|
18.08 percent change
Interval 9.7 to 26.4
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: ITT Population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
MR Prednisone
n=114 Participants
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.
|
IR Prednisone
n=117 Participants
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.
|
|---|---|---|
|
Relative Change From Baseline in SF36 Physical Component Score (PCS) at Week 12
|
19.43 percent change
Interval 7.77 to 31.1
|
21.0 percent change
Interval 11.05 to 30.9
|
Adverse Events
MR Prednisone
IR Prednisone
Serious adverse events
| Measure |
MR Prednisone
n=144 participants at risk
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.
|
IR Prednisone
n=144 participants at risk
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.
|
|---|---|---|
|
General disorders
|
2.8%
4/144
Among serious adverse events (SAEs), only data for total # affected by any SAE is available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for SAEs the preferred term is reported as "Not Available" and System Organ Class as "General Disorders".
|
2.1%
3/144
Among serious adverse events (SAEs), only data for total # affected by any SAE is available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for SAEs the preferred term is reported as "Not Available" and System Organ Class as "General Disorders".
|
Other adverse events
| Measure |
MR Prednisone
n=144 participants at risk
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.
|
IR Prednisone
n=144 participants at risk
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.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
2.8%
4/144
Among serious adverse events (SAEs), only data for total # affected by any SAE is available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for SAEs the preferred term is reported as "Not Available" and System Organ Class as "General Disorders".
|
5.6%
8/144
Among serious adverse events (SAEs), only data for total # affected by any SAE is available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for SAEs the preferred term is reported as "Not Available" and System Organ Class as "General Disorders".
|
|
Immune system disorders
Rheumatoid arthritis
|
7.6%
11/144
Among serious adverse events (SAEs), only data for total # affected by any SAE is available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for SAEs the preferred term is reported as "Not Available" and System Organ Class as "General Disorders".
|
9.0%
13/144
Among serious adverse events (SAEs), only data for total # affected by any SAE is available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for SAEs the preferred term is reported as "Not Available" and System Organ Class as "General Disorders".
|
|
Gastrointestinal disorders
Abdominal pain (upper)
|
3.5%
5/144
Among serious adverse events (SAEs), only data for total # affected by any SAE is available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for SAEs the preferred term is reported as "Not Available" and System Organ Class as "General Disorders".
|
5.6%
8/144
Among serious adverse events (SAEs), only data for total # affected by any SAE is available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for SAEs the preferred term is reported as "Not Available" and System Organ Class as "General Disorders".
|
Additional Information
Merck KGaA Communication Center,
Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place