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

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

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00637780

Enrollment

Registered

2008-03-18

Start date

2010-06-30

Completion date

2014-01-31

Last updated

2017-02-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Arthritis, Juvenile Rheumatoid

Keywords

Sulfasalazine delayed release tablets, azulfidine entabs, Pharmacokinetics, Juvenile Idiopathic Arthritis (JIA)

Brief summary

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.

Interventions

DRUGSulfasalazine

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

6 Years to 17 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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	Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose	Sulfapyridine and 5-aminosalicylic acid (5-ASA) are primary metabolites of sulfasalazine, the study drug.
Sulfapyridine Tmax at Steady State	Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose	Sulfapyridine and 5-ASA are primary metabolites of sulfasalazine, the study drug.
Sulfapyridine AUCtau at Steady State	Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose	Sulfapyridine and 5-ASA are primary metabolites of sulfasalazine, the study drug.
5-aminosalicylic Acid (5-ASA) Steady State Cmax and Cmin	Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose	Sulfapyridine and 5-ASA are primary metabolites of sulfasalazine, the study drug.
5-aminosalicylic Acid (5-ASA) Tmax at Steady State	Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose	Sulfapyridine and 5-ASA are primary metabolites of sulfasalazine, the study drug.
5-aminosalicylic Acid (5-ASA) AUCtau at Steady State	Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose	Sulfapyridine and 5-ASA are primary metabolites of sulfasalazine, the study drug.

Secondary

Measure	Time frame	Description
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs	Screening through to and including 28 calendar days after the last administration of the investigational product	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.
Number of Participants With Laboratory Test Abnormalities	Screening, Day 0, and Day 7	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).
Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria	Screening, Day 0, and Day 7	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.

Countries

Mexico, United States

Participant flow

Recruitment details

The last participant enrolled in 2014 but the study was kept open for another 2 years and enrollment was not stopped. However, by 2016, no additional participants were enrolled and thus the study was closed. As such, the basic results for this study are only prepared in 2016 though last participant's last visit was in 2014.

Participants by arm

Arm	Count
Sulfasalazine in Juvenile Idiopathic Arthritis All participants received sulfasalazine 30-50 milligrams (mg)/kilograms (kg)/day, divided into twice daily (BID) doses, for 6 days. On Day 7, the morning dose was administered at the site in presence of site staff. Sulfasalazine was administered orally in the form of 500-mg tablets.	2
Total	2

Baseline characteristics

Characteristic	Sulfasalazine in Juvenile Idiopathic Arthritis
Age, Continuous	15.0 years STANDARD_DEVIATION 1.4
Gender Female	1 Participants
Gender Male	1 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	0 / 2
serious Total, serious adverse events	0 / 2

Outcome results

Primary