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

Arthritis, Juvenile Rheumatoid Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00279747
• Other study ID #: 107.208
• Status: Completed
• Phase: Phase 3
• First received: January 19, 2006
• Last updated: October 31, 2013
• Start date: September 2000
• Est. completion date: January 2003

Study information

• Verified date: October 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ministry of HealthAustria: EthikkommissionRussia: Ethics CommitteeBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 226
• Est. completion date: January 2003
• Est. primary completion date: January 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 16 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Arthritis, Juvenile Rheumatoid
• Arthritis, Rheumatoid

Intervention

Drug:
• meloxicam 0.25 mg/kg

• meloxicam 0.125 mg/kg

• naproxen 10 mg/kg

Locations

Country	Name	City	State
Austria	Landes-Kinderklinik Linz	Linz
Austria	Gottfried Preyersches Kinderspital d. Stadt Wien	Wien
Austria	Univ.-Klinik für Kinder- und Jugendheilkunde Wien	Wien
Belgium	UZ Gent	Gent
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	Boehringer Ingelheim Investigational Site	Merksem
France	Boehringer Ingelheim Investigational Site	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
Germany	Rheumaklinik Bad Bramstedt GmbH	Bad Bramstedt
Germany	Neurologie	Bremen
Germany	Universität Erlangen	Erlangen
Germany	Martin-Luther-Universität Halle	Halle/Saale
Germany	Boehringer Ingelheim Investigational Site	Hamburg
Germany	Bayrische Julius-Maximilians-Universität	Würzburg
Italy	Ospedale Meyer	Firenze
Italy	Istituto G. Gaslini	Genova
Italy	Istituto Ortopedico Gaetano Pini	Milano
Italy	II Università degli Studi di Napoli	Napoli
Italy	Università Federico II	Napoli
Italy	Clinica Pediatrica I	Padova
Italy	IRCCS Policlinico San Matteo	Pavia
Italy	Ospedale Pediatrico Bambin Gesù	Roma
Italy	IRCCS Burlo Garofalo	Trieste
Russian Federation	Institute of Rheumatology of RAMN	Moscow
Russian Federation	Medical Academy Setchenov	Moscow
Russian Federation	Medical Faculty of Russian People Friendship University	Moscow
Russian Federation	Scientific Research Institute of Pediatric Hematology	Moscow
United Kingdom	Dept. of Child Health	London
United Kingdom	Booth Hall Childrens Hospital	Manchester
United Kingdom	Paediatric Department	Wolverhampton

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Italy,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rates according to ACR Ped 30		after 12 weeks of treatment	No
Secondary	Global assessment of overall disease activity by investigator		up to 12 months	No
Secondary	Parent global assessment of overall well-being		up to 12 months	No
Secondary	Assessment of functional disability by means of Childhood Health Assessment Questionnaire (CHAQ)		up to 12 months	No
Secondary	Number of joints with active arthritis		up to 12 months	No
Secondary	Number of joints with limited range of motion		up to 12 months	No
Secondary	Erythrocyte Sedimentation Rate (ESR)		up to 12 months	No
Secondary	Parent global assessment of arthritis		up to 12 months	No
Secondary	Parent global assessment of pain		up to 12 months	No
Secondary	Children's assessment of discomfort		up to 12 months	No
Secondary	Change in functional classification (Steinbrocker classification)		up to 12 months	No
Secondary	Final global assessment of efficacy by parent		week 12, 12 months	No
Secondary	Final global assessment of efficacy by investigator		week 12, 12 months	No
Secondary	Withdrawals due to inadequate efficacy		up to 12 months	No
Secondary	Paracetamol / acetaminophen consumption		up to 12 months	No
Secondary	Final global assessment of tolerability by parent		week 12, 12 months	No
Secondary	Final global assessment of tolerability by investigator		week 12, 12 months	No
Secondary	Incidence and intensity of adverse events (AEs)		12 months	No
Secondary	Incidence of laboratory adverse events		12 months	No
Secondary	Withdrawal due to adverse event		12 months	No
Secondary	Duration of hospital stay due to gastrointestinal serious adverse event (GI-SAE)		week 12, 12 months	No
Secondary	Duration of hospital stay due to adverse events related to trial drug administration		week 12, 12 months	No
Secondary	Additional visits to a physician due to gastrointestinal adverse event (GI-AE)		week 12, 12 months	No

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