Study To Determine The Pharmacokinetics Of Sulfasalazine In Children With Juvenile Idiopathic Arthritis

Study Overview
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Brief Summary
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This study will characterize the steady state pharmacokinetics of sulfasalazine delayed release tablets in pediatric Juvenile Idiopathic Arthritis patients. Data from this study will fulfill the post approval commitment to the FDA.

Official Title
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An Open Label Non-randomized Study To Characterize The Steady State Pharmacokinetics Of Sulfasalazine Delayed Release Tablets In Children With Juvenile Idiopathic Arthritis

Conditions
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Arthritis, Juvenile Rheumatoid

Intervention / Treatment
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* Drug: Sulfasalazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis of oligoarticular, polyarticular, psoriatic or enthesitis-related JIA as determined by ILAR criteria. Patients who have been continuously treated with generic sulfasalazine delayed release formulation and have tolerated the product for at least 3 months prior to study enrolment and who are switched to Azulfidine-EN at least 8 days prior to Day 0 are eligible. Patients must be at least 6 years of age and has not reached his/her 18th birthday prior to the Baseline Visit (Day 0). Onset of JIA must have occurred prior to the patient's 16th birthday. Patients must weigh at least 20 kg. Patients must be on sulfasalazine 500 mg delayed release tablets and the total daily dose must be within the specified range of 30-60 mg/kg/day with a maximum daily dose of 3 g/day Exclusion Criteria: Patient currently with systemic features of systemic JIA. Hypersensitivity to sulfasalazine , its metabolites, sulfonamides or salicylates. History of sensitivity to heparin or heparin-induced thrombocytopenia. Inability to swallow whole (uncrushed) sulfasalazine 500 mg delayed release tablets as required by protocol

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Sulfasalazine delayed release tablets 30-60 mg/kg/day (divided into BID doses) for 6 days | Drug: Sulfasalazine<br>* Sulfasalazine delayed release tablets 30-60 mg/kg/day (divided into BID doses) for 7 days. Blood sampling for Pharmacokinetic assessment to be performed on Day 7<br>* Other names: AZULFIDINE EN-tabs Tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sulfasalazine Steady State Maximum Plasma Concentration (Cmax) and Predose Concentration (Cmin) |  | Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose | 
| Sulfasalazine Time for Cmax (Tmax) at Steady State |  | Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose | 
| Sulfasalazine Area Under the Concentration-time Profile From Time 0 to Time Tau, the Dosing Interval (AUCtau) at Steady State |  | Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose | 
| Sulfapyridine Steady State Cmax and Cmin | Sulfapyridine and 5-aminosalicylic acid (5-ASA) are primary metabolites of sulfasalazine, the study drug. | Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose | 
| Sulfapyridine Tmax at Steady State | Sulfapyridine and 5-ASA are primary metabolites of sulfasalazine, the study drug. | Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose | 
| Sulfapyridine AUCtau at Steady State | Sulfapyridine and 5-ASA are primary metabolites of sulfasalazine, the study drug. | Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose | 
| 5-aminosalicylic Acid (5-ASA) Steady State Cmax and Cmin | Sulfapyridine and 5-ASA are primary metabolites of sulfasalazine, the study drug. | Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose | 
| 5-aminosalicylic Acid (5-ASA) Tmax at Steady State | Sulfapyridine and 5-ASA are primary metabolites of sulfasalazine, the study drug. | Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose | 
| 5-aminosalicylic Acid (5-ASA) AUCtau at Steady State | Sulfapyridine and 5-ASA are primary metabolites of sulfasalazine, the study drug. | Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAEs are defined as newly occurring AEs or those worsening after first dose. AEs comprised both SAEs and non-SAEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Screening through to and including 28 calendar days after the last administration of the investigational product | 
| Number of Participants With Laboratory Test Abnormalities | Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes,clinical chemistry, and urinalysis (dipstick and microscopy). | Screening, Day 0, and Day 7 | 
| Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Vital sign values which met categorical summarization criteria included: supine/sitting pulse rate less than (<) 40 or more than (>) 120 beats per minute (bpm); erect pulse rate <40 or >140 bpm; changes from baseline in same posture of systolic blood pressure (SBP) more than or equal to (>=) 30 millimeters of mercury (mm Hg) or diastolic blood pressure (DBP) >=20 mm Hg; SBP <90 mm Hg; and DBP <50 mm Hg. | Screening, Day 0, and Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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azulfidine entabs, Pharmacokinetics, Juvenile Idiopathic Arthritis (JIA), Sulfasalazine delayed release tablets