A One Year Double-blind Trial to Investigate the Efficacy and Safety of Meloxicam Oral Suspension in Juvenile Rheumatoid Arthritis (JRA/JIA)

A One Year Double-blind Trial to Investigate the Efficacy and Safety of Meloxicam Oral Suspension 0.25mg/kg and 0.125 mg/kg Administered Once Daily in Comparison to Naproxen Oral Suspension 5mg/kg Administered Twice Daily in Children With Juvenile Rheumatoid Arthritis.

A one year double-blind trial to investigate the efficacy and safety of meloxicam oral suspension 0.25 mg/kg and 0.125 mg/kg administered once daily in comparison to naproxen oral suspension 5 mg/kg administered twice daily in children with Juvenile Rheumatoid Arthritis.

Study Overview

• Status: Completed
• Conditions: Arthritis, Juvenile Rheumatoid
• Intervention / Treatment: Drug: meloxicam 0.25 mg/kg; Drug: meloxicam 0.125 mg/kg; Drug: naproxen 10 mg/kg

Detailed Description

Objective: In an international, multicenter, double-blind, randomized clinical trial we evaluated the short-term (3 months) and long term (12 months) efficacy and safety of two doses of meloxicam oral suspension compared with naproxen in children with oligo and polyarticular course juvenile idiopathic arthritis (JIA).

Methods: Children with active oligo or polyarticular course JIA, requiring therapy with an NSAID were eligible for this trial. Patients were randomly allocated to therapy with meloxicam oral suspension 0.125 mg/kg body weight in single daily dose, meloxicam 0.25 mg/kg body weight in single daily dose, or naproxen 10 mg/kg body weight in two daily doses. The trial drugs were administered in a double-blind, double-dummy design for up to 12 months. Response rates were determined according to the American College of Rheumatology Pediatric 30% definition of improvement (ACR Ped 30). Safety parameters were assessed by evaluation of the adverse events in the 3 groups.

Study Hypothesis:

The null hypothesis of interest is that the magnitude of response with regard to the primary endpoint is equivalent between the treatment groups. The alternative is that there is any difference (two-sided) between any of the treatment groups.

Comparison(s):

Naproxen oral suspension 10 mg/kg body weight.

• Study Type: Interventional
• Enrollment: 226
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, 4020
    • Landes-Kinderklinik Linz
  • Wien, Austria, 1090
    • Univ.-Klinik für Kinder- und Jugendheilkunde Wien
  • Wien, Austria, 1100 Wien
    • Gottfried Preyersches Kinderspital d. Stadt Wien
• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • U.Z. Gasthuisberg
  • Merksem, Belgium, 2170
    • Boehringer Ingelheim Investigational Site
• France
  • Angers, France
    • Boehringer Ingelheim Investigational Site
  • Lille, France
    • Boehringer Ingelheim Investigational Site
  • Marseille, France
    • Boehringer Ingelheim Investigational Site
  • Paris, France
    • Boehringer Ingelheim Investigational Site
  • Strasbourg, France
    • Boehringer Ingelheim Investigational Site
  • Vandoeuvre les Nancy, France
    • Boehringer Ingelheim Investigational Site
• Germany
  • Bad Bramstedt, Germany, 24572
    • Rheumaklinik Bad Bramstedt GmbH
  • Bremen, Germany, 28325
    • Neurologie
  • Erlangen, Germany, 91054
    • Universitat Erlangen
  • Halle/Saale, Germany, 06097
    • Martin-Luther-Universität Halle
  • Hamburg, Germany, 22081
    • Boehringer Ingelheim Investigational Site
  • Würzburg, Germany, 97080
    • Bayrische Julius-Maximilians-Universität
• Italy
  • Firenze, Italy, 50132
    • Ospedale Meyer
  • Genova, Italy, 16147
    • Istituto G. Gaslini
  • Milano, Italy, 20122
    • Istituto Ortopedico Gaetano Pini
  • Napoli, Italy, 80131
    • Università Federico II
  • Napoli, Italy, 80129
    • II Universita degli Studi di Napoli
  • Padova, Italy, 35128
    • Clinica Pediatrica I
  • Pavia, Italy, 27100
    • IRCCS Policlinico San Matteo
  • Roma, Italy, 00165
    • Ospedale Pediatrico Bambin Gesù
  • Trieste, Italy, 34137
    • IRCCS Burlo Garofalo
• Russian Federation
  • Moscow, Russian Federation, 115522
    • Institute of Rheumatology of RAMN
  • Moscow, Russian Federation, 117049
    • Medical Faculty of Russian People Friendship University
  • Moscow, Russian Federation, 117513
    • Scientific Research Institute of Pediatric Hematology
  • Moscow, Russian Federation, 119435
    • Medical Academy Setchenov
• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Dept. of Child Health
  • Manchester, United Kingdom, M9 7AA
    • Booth Hall Childrens Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • Paediatric Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female outpatients and inpatients aged 2 to 16 years

• Diagnosis of idiopathic arthritis of childhood by ILAR criteria:

  • Age of onset less than 16 years
  • Arthritis in one or more joints defined as swelling, or - if no swelling is present - limitation in range of joint movement with joint pain or tenderness, which is not due to primary mechanical disorders
  • Duration of the disease > 6 weeks
  • Type of onset of disease during the first 6 months classified as polyarthritis (5 joints or more; rheumatoid factor positive or negative), oligoarthritis (4 joints or fewer) or systemic arthritis
• Oligoarthritic, extended oligoarthritic or polyarthritic current course of disease
• Active arthritis as defined above of at least 2 joints
• At least 2 other abnormal variables of any of the 5 remaining core set parameters. The physician and the parent ratings must be at least 10 mm on a 100 mm VAS scale and the CHAQ score more than 0.

• Patients requiring therapy with NSAIDs, i.e., the patient fits into one of the following categories:

  • New onset patient
  • Patient in remission, but experiencing a flare and now requiring an NSAID
  • Patient with insufficient therapeutic effect (ITE) or intolerability to another NSAID (other than Naproxen) and now must be changed
• Written informed permission given by the parent(s) or the subjects legally authorised representative in accordance with local legislation and ICH GCP
• Active assent given by the patient if the child is capable of understanding the given information (applies to children who have reached an intellectual age of 7 years or greater)

Exclusion Criteria:

• Patients with systemic course of JRA (intermittent fever with or without rash or other organ involvement) or with current systemic involvement
• All rheumatic diseases not covered by the inclusion criteria
• Any finding indicating that the patient has a clinically significant other disease than JRA at the time of enrollment
• Patients with abnormal, clinically relevant laboratory values not related to their JRA
• Pregnancy or breast feeding
• Women of childbearing potential not using adequate contraception precaution: attention should be drawn to reports that NSAIDs were reported to decrease the effectiveness of intrauterine devices (R95-0164)
• History of bleeding disorders, gastrointestinal bleeding or cerebrovascular bleeding
• Active peptic ulcer within the last 6 months
• Treatment with more than one SAARD/DMARD (slow-acting antirheumatic drug/disease-modifying antirheumatic drug) during the last 3 months prior to study entry
• Change in treatment with SAARDs/DMARDs during the last 3 months prior to study entry or intended change during the trial duration
• Change in treatment with corticosteroids during the last month prior to study entry or intended change during the trial duration with exception of local therapy for uveitis

• One of the following therapies during the last 3 months prior to study entry or their intended use during the trial treatment period

  • Systemic treatment (except for intra-articular injections) with corticosteroids at a dose higher than 10 mg/day or 0.2 mg/kg/day (prednisone equivalent), respectively (whichever is lower)
  • Treatment with hydroxychloroquine at a dose higher than 10 mg/kg/day
  • Treatment with cyclosporine at a dose higher than 5 mg/kg/day
  • Treatment with methotrexate at a dose higher than 15 mg/m2/week
  • Treatment with other cytotoxic agents, gold compounds, D-penicillamine, Enbrel (etanercept), biologic agents and experimentals
• Intra-articular injections of corticosteroids during the last month prior to study entry and intended injections during the first 4 weeks of the trial treatment period
• Concomitant administration of other NSAIDs (including topical forms for skin with exception of local therapy for uveitis) or analgesic agents except paracetamol or acetaminophen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rates according to ACR Ped 30	after 12 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Global assessment of overall disease activity by investigator	up to 12 months
Parent global assessment of overall well-being	up to 12 months
Assessment of functional disability by means of Childhood Health Assessment Questionnaire (CHAQ)	up to 12 months
Number of joints with active arthritis	up to 12 months
Number of joints with limited range of motion	up to 12 months
Erythrocyte Sedimentation Rate (ESR)	up to 12 months
Parent global assessment of arthritis	up to 12 months
Parent global assessment of pain	up to 12 months
Children's assessment of discomfort	up to 12 months
Change in functional classification (Steinbrocker classification)	up to 12 months
Final global assessment of efficacy by parent	week 12, 12 months
Final global assessment of efficacy by investigator	week 12, 12 months
Withdrawals due to inadequate efficacy	up to 12 months
Paracetamol / acetaminophen consumption	up to 12 months
Final global assessment of tolerability by parent	week 12, 12 months
Final global assessment of tolerability by investigator	week 12, 12 months
Incidence and intensity of adverse events (AEs)	12 months
Incidence of laboratory adverse events	12 months
Withdrawal due to adverse event	12 months
Duration of hospital stay due to gastrointestinal serious adverse event (GI-SAE)	week 12, 12 months
Duration of hospital stay due to adverse events related to trial drug administration	week 12, 12 months
Additional visits to a physician due to gastrointestinal adverse event (GI-AE)	week 12, 12 months

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2000
• Primary Completion (Actual): January 1, 2003
• Study Completion (Actual): January 1, 2003

Study Registration Dates

• First Submitted: January 19, 2006
• First Submitted That Met QC Criteria: January 19, 2006
• First Posted (Estimate): January 20, 2006

Study Record Updates

• Last Update Posted (Estimate): November 1, 2013
• Last Update Submitted That Met QC Criteria: October 31, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Juvenile; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Gout Suppressants; Naproxen; Meloxicam
• Other Study ID Numbers: 107.208