Efficacy of Lodotra®(Prednisone) in Reduction of Morning Stiffness Duration(K-IMPROvE)

A New Modified-Release Tablet Formulation of Prednisone in Patients With Rheumatoid Arthritis- Multicenter, Phase IV, Interventional Study to Assess Reduction of Morning Stiffness

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).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Lodotra®

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

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Kyungkido
    • Pyeongchon, Kyungkido, Korea, Republic of
      • Hallym University Sacred Heart Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Modified release prednisone; Single arm / Lodotra	Drug: 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; Other Names: Modified Release Prednisone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 12 weeks
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.	12 weeks

Collaborators and Investigators

• Sponsor: Mundipharma Korea Ltd
• Investigators: Principal Investigator: Seungjae Hong, PhD, KyungHee University Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: February 14, 2014
• First Submitted That Met QC Criteria: February 24, 2014
• First Posted (Estimate): February 26, 2014

Study Record Updates

• Last Update Posted (Estimate): August 8, 2016
• Last Update Submitted That Met QC Criteria: August 5, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: RA, MS, Safety, Efficacy, MR prednisone
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: LOD13-KR-401