A One Year Double-Blind Trial to Investigate the Efficacy and Safety of Meloxicam Oral Suspension in JRA/JIA

Condition(s) targeted: Arthritis, Juvenile Rheumatoid

Intervention: meloxicam 0.25 mg/kg (Drug); meloxicam 0.125 mg/kg (Drug); naproxen 10 mg/kg (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Boehringer Ingelheim Pharmaceuticals

Official(s) and/or principal investigator(s):
Boehringer Ingelheim Study Coordinator, Study Chair, Affiliation: B.I. Pharma GmbH & Co. KG

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

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 design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Response rates according to ACR Ped 30

Secondary outcome: investigator global assessment of overall disease activity, parent global assessment of overall well-being, number of joints with active arthritis, number of joints with limited range of motion, assessment of functional disability by means of CHAQ

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.

Minimum age: 2 Years. Maximum age: 16 Years. Gender(s): Both.

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

Univ.-Klinik für Kinder- und Jugendheilkunde Wien, Wien 1090, Austria

Gottfried Preyersches Kinderspital d. Stadt Wien, Wien 1100 Wien, Austria

Landes-Kinderklinik Linz, Linz 4020, Austria

UZ Gent, Gent 9000, Belgium

U.Z. Gasthuisberg, Leuven 3000, Belgium

Boehringer Ingelheim Investigational Site, Merksem 2170, Belgium

Boehringer Ingelheim Investigational Site, Paris, France

Boehringer Ingelheim Investigational Site, Vandoeuvre les Nancy, France

Boehringer Ingelheim Investigational Site, Marseille, France

Boehringer Ingelheim Investigational Site, Strasbourg, France

Boehringer Ingelheim Investigational Site, Lille, France

Boehringer Ingelheim Investigational Site, Angers, France

Boehringer Ingelheim Investigational Site, Hamburg 22081, Germany

Rheumaklinik Bad Bramstedt GmbH, Bad Bramstedt 24572, Germany

Neurologie, Bremen 28325, Germany

Bayrische Julius-Maximilians-Universität, Würzburg 97080, Germany

Martin-Luther-Universität Halle, Halle/Saale 06097, Germany

Universität Erlangen, Erlangen 91054, Germany

IRCCS Policlinico San Matteo, PAVIA 27100, Italy

Ospedale Pediatrico Bambin Gesù, ROMA 00165, Italy

Ospedale Meyer, FIRENZE 50132, Italy

Istituto Ortopedico Gaetano Pini, MILANO 20122, Italy

IRCCS Burlo Garofalo, TRIESTE 34137, Italy

Clinica Pediatrica I, PADOVA 35128, Italy

II Università degli Studi di Napoli, NAPOLI 80129, Italy

Istituto G. Gaslini, GENOVA 16147, Italy

Università Federico II, NAPOLI 80131, Italy

Institute of Rheumatology of RAMN, Moscow 115522, Russian Federation

Medical Academy Setchenov, Moscow 119435, Russian Federation

Scientific Research Institute of Pediatric Hematology, Moscow 117513, Russian Federation

Medical Faculty of Russian People Friendship University, Moscow 117049, Russian Federation

Dept. of Child Health, London WC1N 3JH, United Kingdom

Booth Hall Childrens Hospital, Manchester M9 7AA, United Kingdom

Paediatric Department, Wolverhampton WV10 0QP, United Kingdom

Starting date: September 2000
Ending date: January 2003
Last updated: April 2, 2008