Clinical trial NCT00279747: A One Year Double-blind Trial to Investigate the Efficacy and Safety of Meloxicam Oral Suspension in Juvenile Rheumatoid Arthritis (JRA/JIA)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Juvenile Rheumatoid
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2006-01-20
Enrollment: 226
Sex: ALL
Minimum age (years): 2
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Response rates according to ACR Ped 30
timeFrame: after 12 weeks of treatment
Secondary outcomes:
measure: Global assessment of overall disease activity by investigator
timeFrame: up to 12 months
measure: Parent global assessment of overall well-being
timeFrame: up to 12 months
measure: Assessment of functional disability by means of Childhood Health Assessment Questionnaire (CHAQ)
timeFrame: up to 12 months
measure: Number of joints with active arthritis
timeFrame: up to 12 months
measure: Number of joints with limited range of motion
timeFrame: up to 12 months
measure: Erythrocyte Sedimentation Rate (ESR)
timeFrame: up to 12 months
measure: Parent global assessment of arthritis
timeFrame: up to 12 months
measure: Parent global assessment of pain
timeFrame: up to 12 months
measure: Children's assessment of discomfort
timeFrame: up to 12 months
measure: Change in functional classification (Steinbrocker classification)
timeFrame: up to 12 months
measure: Final global assessment of efficacy by parent
timeFrame: week 12, 12 months
measure: Final global assessment of efficacy by investigator
timeFrame: week 12, 12 months
measure: Withdrawals due to inadequate efficacy
timeFrame: up to 12 months
measure: Paracetamol / acetaminophen consumption
timeFrame: up to 12 months
measure: Final global assessment of tolerability by parent
timeFrame: week 12, 12 months
measure: Final global assessment of tolerability by investigator
timeFrame: week 12, 12 months
measure: Incidence and intensity of adverse events (AEs)
timeFrame: 12 months
measure: Incidence of laboratory adverse events
timeFrame: 12 months
measure: Withdrawal due to adverse event
timeFrame: 12 months
measure: Duration of hospital stay due to gastrointestinal serious adverse event (GI-SAE)
timeFrame: week 12, 12 months
measure: Duration of hospital stay due to adverse events related to trial drug administration
timeFrame: week 12, 12 months
measure: Additional visits to a physician due to gastrointestinal adverse event (GI-AE)
timeFrame: week 12, 12 months
Other outcomes:
Locations:
city: Linz
country: Austria
facility: Landes-Kinderklinik Linz
city: Wien
country: Austria
facility: Univ.-Klinik für Kinder- und Jugendheilkunde Wien
city: Wien
country: Austria
facility: Gottfried Preyersches Kinderspital d. Stadt Wien
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Merksem
country: Belgium
facility: Boehringer Ingelheim Investigational Site
city: Angers
country: France
facility: Boehringer Ingelheim Investigational Site
city: Lille
country: France
facility: Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: Boehringer Ingelheim Investigational Site
city: Strasbourg
country: France
facility: Boehringer Ingelheim Investigational Site
city: Vandoeuvre les Nancy
country: France
facility: Boehringer Ingelheim Investigational Site
city: Bad Bramstedt
country: Germany
facility: Rheumaklinik Bad Bramstedt GmbH
city: Bremen
country: Germany
facility: Neurologie
city: Erlangen
country: Germany
facility: Universität Erlangen
city: Halle/Saale
country: Germany
facility: Martin-Luther-Universität Halle
city: Hamburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Würzburg
country: Germany
facility: Bayrische Julius-Maximilians-Universität
city: Firenze
country: Italy
facility: Ospedale Meyer
city: Genova
country: Italy
facility: Istituto G. Gaslini
city: Milano
country: Italy
facility: Istituto Ortopedico Gaetano Pini
city: Napoli
country: Italy
facility: II Università degli Studi di Napoli
city: Napoli
country: Italy
facility: Università Federico II
city: Padova
country: Italy
facility: Clinica Pediatrica I
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambin Gesù
city: Trieste
country: Italy
facility: IRCCS Burlo Garofalo
city: Moscow
country: Russian Federation
facility: Institute of Rheumatology of RAMN
city: Moscow
country: Russian Federation
facility: Medical Faculty of Russian People Friendship University
city: Moscow
country: Russian Federation
facility: Scientific Research Institute of Pediatric Hematology
city: Moscow
country: Russian Federation
facility: Medical Academy Setchenov
city: London
country: United Kingdom
facility: Dept. of Child Health
city: Manchester
country: United Kingdom
facility: Booth Hall Childrens Hospital
city: Wolverhampton
country: United Kingdom
facility: Paediatric Department
Study officials:
affiliation: B.I. Pharma GmbH & Co. KG
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: