Rheumatoid ArthritisPhase 3NCT00146640
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 Phase 3 study testing MR Prednisone and IR Prednisone in people with Rheumatoid Arthritis, run by Merck KGaA, Darmstadt, Germany at 24 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- MR Prednisone and IR Prednisone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 288 participants
- Where
- 24 sitesin 2 countries
- Study dates
- 31 Aug 2004to 31 Jan 2007
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- All contra-indications for glucocorticoids
- Pregnancy
- Concomitant treatment with biologics
- Intra-articular injections or synovectomy within the previous 4 months
Trial locations and contacts
24 sites in 2 countries.
24 sites in 2 countries
Germany15 sites
Research Site
Aachen
Research Site
Bad Kreuznach
Research Site
Berlin
Research Site
Cologne
Research Site
Dresden
Research Site
Düsseldorf
Research Site
Erlangen
Research Site
Frankfurt am Main
Research Site
Hamburg
Research Site
Hanover
Research Site
Jena
Research Site
Leipzig
Research Site
München
Research Site
Ratingen
Research Site
Rostock
Poland9 sites
Research Site
Bialystok
Research Site
Katowice
Research Site
Krakow
Research Site
Lublin
Research Site
Poznan
Research Site
Sopot
Research Site
Torun
Research Site
Warsaw
Research Site
Wroclaw
About this study
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
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- MR Prednisone, IR Prednisone, Placebo - MR Prednisone, Placebo - IR Prednisone
- Keywords
- active disease, morning stiffness of joints, nighttime application of prednisone, modified release prednisone
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MR PrednisoneDrug
Participants will receive tablets containing MR prednisone (to achieve the appropriate dose of 3-10 milligrams [mg] prednisone per day) at bed time.
IR PrednisoneDrug
Participants will receive tablets containing IR prednisone (to achieve the appropriate dose of 3-10 mg prednisone per day) in the morning.
Placebo - MR PrednisoneDrug
Participants will receive placebo matching to MR prednisone tablet at bed time.
Placebo - IR PrednisoneDrug
Participants will receive placebo matching to IR prednisone tablet in the morning.
| Study group | Role | What they receive |
|---|---|---|
| MR Prednisone | Experimental | Participants will receive MR prednisone at bed time and placebo matching to IR prednisone in the morning. Total duration of double blind treatment will be 12 weeks. Receives: Drug: MR Prednisone; Drug: Placebo - IR Prednisone |
| IR Prednisone | Active comparator | Participants will receive IR prednisone in the morning and placebo matching to MR prednisone at bed time. Total duration of double blind treatment will be 12 weeks. Receives: Drug: IR Prednisone; Drug: Placebo - MR Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 12
Secondary outcomes (7)
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.
Measured: Baseline, Week 12
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.
Measured: Week 12
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2005 (estimated)
- Study start31 Aug 2004
- Primary completion31 Jan 2007
- Study completion31 Jan 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 288 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00146640
- Sponsor's protocol ID
- EMR 62215-003
- Status last verified
- Jun 2018
- First submitted
- 6 Sep 2005
- Last updated
- 3 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Alten R, Doring 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/jrheum.100051. Epub 2010 Aug 3.
PubMed 20682671Buttgereit 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 (CAPRA-1): a double-blind, randomised controlled trial. Lancet. 2008 Jan 19;371(9608):205-14. doi: 10.1016/S0140-6736(08)60132-4.
PubMed 18207016
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00146640
- Acronym / sponsor ID
- EMR 62215-003
- Conditions
- Rheumatoid Arthritis
- Keywords
- active disease, morning stiffness of joints, nighttime application of prednisone, modified release prednisone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 288 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 31 Aug 2004 (actual)
- Primary completion
- 31 Jan 2007 (actual)
- Study completion
- 31 Jan 2007 (actual)
- First posted
- 7 Sep 2005 (estimated)
- Results
- Posted 29 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MR Prednisone | Experimental | Drug: MR Prednisone, Drug: Placebo - IR PrednisoneParticipants will receive MR prednisone at bed time and placebo matching to IR prednisone in the morning. Total duration of double blind treatment will be 12 weeks. |
| IR Prednisone | Active comparator | Drug: IR Prednisone, Drug: Placebo - MR PrednisoneParticipants will receive IR prednisone in the morning and placebo matching to MR prednisone at bed time. Total duration of double blind treatment will be 12 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- All contra-indications for glucocorticoids
- Pregnancy
- Concomitant treatment with biologics
- Intra-articular injections or synovectomy within the previous 4 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MR PrednisoneParticipants will receive tablets containing MR prednisone (to achieve the appropriate dose of 3-10 milligrams [mg] prednisone per day) at bed time. | Drug | MR Prednisone |
| IR PrednisoneParticipants will receive tablets containing IR prednisone (to achieve the appropriate dose of 3-10 mg prednisone per day) in the morning. | Drug | IR Prednisone |
| Placebo - MR PrednisoneParticipants will receive placebo matching to MR prednisone tablet at bed time. | Drug | IR Prednisone |
| Placebo - IR PrednisoneParticipants will receive placebo matching to IR prednisone tablet in the morning. | Drug | MR Prednisone |
Primary outcome
Relative Change From Baseline in Duration of Morning Stiffness at Week 12
Time frame: 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.
7 secondary outcomes
Relative Change From Baseline in 28-Joint Disease Activity Score (DAS28) at Week 12
Time frame: Baseline, Week 12
Percentage of Participants With Recurrence of Joint Stiffness at Week 12
Time frame: Week 12
Relative Change From Baseline in Pain Intensity at Week 12
Time frame: Baseline, Week 12
Relative Change From Baseline in Quality of Sleep at Week 12
Time frame: Baseline, Week 12
Relative Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12
Time frame: Baseline, Week 12
Relative Change From Baseline in Short-Form 36 (SF36) Mental Component Score (MCS) at Week 12
Time frame: Baseline, Week 12
Relative Change From Baseline in SF36 Physical Component Score (PCS) at Week 12
Time frame: Baseline, Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20682671Alten R, Doring 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/jrheum.100051. Epub 2010 Aug 3.
- Results publication: PubMed 18207016Buttgereit 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 (CAPRA-1): a double-blind, randomised controlled trial. Lancet. 2008 Jan 19;371(9608):205-14. doi: 10.1016/S0140-6736(08)60132-4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck KGaA, Darmstadt, Germany
24 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing MR Prednisone and IR Prednisone in people with Rheumatoid Arthritis, run by Merck KGaA, Darmstadt, Germany at 24 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Germany, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative Change From Baseline in Duration of Morning Stiffness at Week 12 (time frame: Baseline, Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00146640, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2018.