Rheumatoid Arthritis
Conditions
Keywords
RA, MS, Safety, Efficacy, MR prednisone
Brief summary
This study is multicenter, Ph IV, single arm, interventional study to assess relative reduction of morning stiffness of Lodotra® in Rheumatoid Arthritis patients.Study medication will start after study visit at baseline (week 0, visit 1) and follow-up visit will be after 2, 6 and 12 weeks after treatment (visit 2,3,4).
Detailed description
Test Treatment, Dose, and Mode of Administration: Starting dose is 10mg, and depending on the clinical symptoms and the patient's response, the initial dose can quickly be reduced to a lower maintenance dose. When changing over from the standard regimen (glucocorticoid administration in the morning) to Lodotra® administered at bedtime (at about 10 pm), the same dose (in mg prednisone equivalent) should be maintained, if the subject has taken stable dose within 30 days. Lodotra® dose cannot exceed more than 10mg. Lodotra® should be taken at bedtime (at about 10 pm), with or after the evening meal and be swallowed whole with sufficient liquid. If more than 2 - 3 hours have passed since the evening meal, it is recommended to take Lodotra® with a light meal or snack. Modified-release tablets are not to be broken, divided or chewed. Treatment procedure:At Visit 1(week 0), subjects who qualify for entry into the study will medicated to Lodotra® starting dose of 10 mg daily. (Written informed consent has to be obtained, and subjects will undergo complete evaluation for study eligibility) No dose increase will be allowed for more than 10mg
Interventions
DRUGLodotra®
Single arm will be received below oral 10mg tablet daily and maximum 10mg/d depending on the clinical symptoms and the patient's response
Sponsors
Mundipharma Korea Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients who are diagnosed more than 3 months * Morning stiffness on previous treatment with or without oral steroids (below or equal to 10mg per day, methylprednisolone doses were converted into prednisone doses as follows: prednisone dosed=methylprednisolone dose\*1.25), average daily duration of 45 min or more. * Average daily maximum pain intensity score (100 mm VAS) of 30mm or more. * DAS-ESR ≥3.2 * On DMARD treatment including MTX for ≥3months and stable treatment dose within the past 30 days. There are no limitations on number of DMARDs treatment.(Except patients who have experience of adverse drug reaction of MTX or difficulty to administer MTX due to disease specific condition.) * Able to perform study procedures and given written informed consent. * Naïve patients with Prednisone MR(Lodotra® ) or patients not treat with Prednisone MR(Lodotra®) within 4 weeks(28days) * Subject who keeps to administer study drug at 22±30 daily * Subject who provide signed and dated written voluntary informed consent
Exclusion criteria
* Patients who suffers from another disease, which requires glucocorticoid treatment during the study period. * Synovectomy within 4 months prior to study start. * Patients who underwent joint injections on only fingers and wrists(both sides) within 4 weeks prior to first visit. Clinically significant disease which, in the investigator's opinion, would exclude the subject from the study. * Significant renal impairment (serum creatinine\>2.0mg/dl) * Significant hepatic impairment (\>3 times the upper limit of normal range in each site) * All contra-indications for glucocorticoids.(established new osteoporotic fractures history of corticoid psychosis, herpes simplex and herpes zoster, varicella infection) * Uncontrolled DM(HbA1c\>8.0) * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. UNLESS they are: * women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner * women whose partners have been sterilized by vasectomy or other means * two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent. * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test * Participation in another clinical study within the past 30 days * Known hypersensitivity to prednisone * Infection patients without effective antimicrobial and systemic mycosis infection patients(infection might be aggravated due to suppression of immunologic function.) * Patients with immunization with live vaccines within 2 weeks of enrollment or planned during the study * Since this drug contains glucose, patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Morning Stiffness Duration at Week 12 as Assessed by Patient Diary | Baseline and 12 weeks | Data for the duration of morning stiffness will be obtained from patient diaries. Duration of morning stiffness will be from wake-up time to time of resolution of morning stiffness. Relative reduction rate of the morning stiffness duration from baseline to Week 12 of the study drug treatment was calculated for this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Baseline Severity of Morning Stiffness at Week 12 Using Visual Analog Scale (VAS) Scale | Baseline and 12 weeks | The VAS is a 100 mm line ranging from 0 mm (no pain) on the left end and 100 mm (worst pain) on the right end. Subjects marked on the line to indicate their pain severity. The distance in mm was measured from the left end to the subject's marking. |
| Change of Functional Disability Index of the Korea Health Assessment Questionnaire (KHAQ) From Baseline to Week 12 | 12 weeks | Change in KHAQ score from baseline to Week 12 post-treatment: KHAQ is composed of 8 functional disability indices. The scale for each index is from 0 (without any difficulty) to 3 (unable to do). Scores for each disability index were summed to obtain the total score for each subject, ranging between 0 to 24, with higher scores reflecting higher functional disability. The scores were then averaged across all subjects. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Modified Release Prednisone Single arm / Lodotra
Lodotra®: Single arm will be received below oral 10mg tablet daily and maximum 10mg/d depending on the clinical symptoms and the patient's response | 145 |
| Total | 145 |
Baseline characteristics
| Characteristic | Modified Release Prednisone |
|---|---|
| Age, Continuous | 55.41 participant STANDARD_DEVIATION 11.79 |
| Region of Enrollment Korea, Republic of | 145 participants |
| Sex: Female, Male Female | 113 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 51 / 145 |
| serious Total, serious adverse events | 5 / 145 |
Outcome results
Primary
Change From Baseline in Morning Stiffness Duration at Week 12 as Assessed by Patient Diary
Data for the duration of morning stiffness will be obtained from patient diaries. Duration of morning stiffness will be from wake-up time to time of resolution of morning stiffness. Relative reduction rate of the morning stiffness duration from baseline to Week 12 of the study drug treatment was calculated for this outcome measure.
Time frame: Baseline and 12 weeks
Population: ITT set = 145 patients. Missing data was handled as LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modified Release Prednisone | Change From Baseline in Morning Stiffness Duration at Week 12 as Assessed by Patient Diary | -16.76 minutes | Standard Deviation 3.352 |
Secondary
Change of Baseline Severity of Morning Stiffness at Week 12 Using Visual Analog Scale (VAS) Scale
The VAS is a 100 mm line ranging from 0 mm (no pain) on the left end and 100 mm (worst pain) on the right end. Subjects marked on the line to indicate their pain severity. The distance in mm was measured from the left end to the subject's marking.
Time frame: Baseline and 12 weeks
Population: ITT population was 145, but 3 patients were not assessed for primary efficacy parameter of morning stiffness severity. So, Last Observation Carried Forward (LOCF) was not done for these 3 patients after baseline . Other patients' missing data were handled using LOCF method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modified Release Prednisone | Change of Baseline Severity of Morning Stiffness at Week 12 Using Visual Analog Scale (VAS) Scale | -25.70 mm | Standard Deviation 25.87 |
Secondary
Change of Functional Disability Index of the Korea Health Assessment Questionnaire (KHAQ) From Baseline to Week 12
Change in KHAQ score from baseline to Week 12 post-treatment: KHAQ is composed of 8 functional disability indices. The scale for each index is from 0 (without any difficulty) to 3 (unable to do). Scores for each disability index were summed to obtain the total score for each subject, ranging between 0 to 24, with higher scores reflecting higher functional disability. The scores were then averaged across all subjects.
Time frame: 12 weeks
Population: ITT set was 145 patients, but 11 patients data was not assessed except baseline score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modified Release Prednisone | Change of Functional Disability Index of the Korea Health Assessment Questionnaire (KHAQ) From Baseline to Week 12 | -4.76 scores on a scale | Standard Deviation 8.16 |