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

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00637780
• Collaborator: (none)
• Enrollment: 2
• Locations: 2
• Arm: 1
• Duration (Months): 43
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Arthritis, Juvenile Rheumatoid	Drug: Sulfasalazine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Non-randomized Study To Characterize The Steady State Pharmacokinetics Of Sulfasalazine Delayed Release Tablets In Children With Juvenile Idiopathic Arthritis
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Sulfasalazine delayed release tablets 30-60 mg/kg/day (divided into BID doses) for 6 days	Drug: Sulfasalazine; 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; Other Names: AZULFIDINE EN-tabs Tablets

Outcome Measures

Primary Outcome Measures

1. Sulfasalazine Steady State Maximum Plasma Concentration (Cmax) and Predose Concentration (Cmin) [Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose]

2. Sulfasalazine Time for Cmax (Tmax) at Steady State [Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose]

3. 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]

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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 Outcome Measures

1. 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.

2. 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).

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
2	Private Office	Guadalajara	Jalisco	Mexico	44650

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00637780
• Other Study ID Numbers: A0031005
• First Posted: Mar 18, 2008
• Last Update Posted: Feb 23, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Pfizer: Sulfasalazine delayed release tablets; azulfidine entabs; Pharmacokinetics; Juvenile Idiopathic Arthritis (JIA)
• Additional relevant MeSH terms: Arthritis; Arthritis, Juvenile; Sulfasalazine

Study Results

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.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Overall Participants	2
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.0 (1.4)
Gender (Count of Participants)
Female	1 50%
Male	1 50%

Outcome Measures

1. Primary Outcome

Title	Sulfasalazine Steady State Maximum Plasma Concentration (Cmax) and Predose Concentration (Cmin)
Time Frame	Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose

Outcome Measure Data

Analysis Population Description

The 2 participants who were enrolled and completed the study at the time of study termination were included in all analyses.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Measure Participants	2
Cmax - Value 1	17.6
Cmax - Value 2	4.51
Cmin - Value 1	4.28
Cmin - Value 2	0.988

2. Primary Outcome

Title	Sulfasalazine Time for Cmax (Tmax) at Steady State
Time Frame	Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose

Outcome Measure Data

Analysis Population Description

The 2 participants who were enrolled and completed the study at the time of study termination were included in all analyses.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Measure Participants	2
Value 1	2.02
Value 2	5.92

3. Primary Outcome

Title	Sulfasalazine Area Under the Concentration-time Profile From Time 0 to Time Tau, the Dosing Interval (AUCtau) at Steady State
Time Frame	Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose

Outcome Measure Data

Analysis Population Description

The 2 participants who were enrolled and completed the study at the time of study termination were included in all analyses.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Measure Participants	2
Value 1	110
Value 2	34.7

4. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The 2 participants who were enrolled and completed the study at the time of study termination were included in all analyses.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Measure Participants	2
Cmax - Value 1	21.7
Cmax - Value 2	7.68
Cmin - Value 1	14.7
Cmin - Value 2	4.79

5. Primary Outcome

Title	Sulfapyridine Tmax at Steady State
Description	Sulfapyridine and 5-ASA are primary metabolites of sulfasalazine, the study drug.
Time Frame	Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose

Outcome Measure Data

Analysis Population Description

The 2 participants who were enrolled and completed the study at the time of study termination were included in all analyses.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Measure Participants	2
Value 1	4.00
Value 2	11.9

6. Primary Outcome

Title	Sulfapyridine AUCtau at Steady State
Description	Sulfapyridine and 5-ASA are primary metabolites of sulfasalazine, the study drug.
Time Frame	Day 7 predose, and 2, 4, 6, 10, and 12 hours postdose

Outcome Measure Data

Analysis Population Description

The 2 participants who were enrolled and completed the study at the time of study termination were included in all analyses.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Measure Participants	2
Value 1	232
Value 2	67.3

7. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The 2 participants who were enrolled and completed the study at the time of study termination were included in all analyses.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Measure Participants	2
Cmax - Value 1	0.208
Cmax - Value 2	0.0982
Cmin - Value 1	0.0439
Cmin - Value 2	0.0816

8. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The 2 participants who were enrolled and completed the study at the time of study termination were included in all analyses.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Measure Participants	2
Value 1	0.000
Value 2	11.9

9. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The 2 participants who were enrolled and completed the study at the time of study termination were included in all analyses.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Measure Participants	2
Value 1	1.63
Value 2	1.04

10. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs
Description	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.
Time Frame	Screening through to and including 28 calendar days after the last administration of the investigational product

Outcome Measure Data

Analysis Population Description

The 2 participants who were enrolled and completed the study at the time of study termination were included in all analyses.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Measure Participants	2
TEAEs	0 0%
SAEs	0 0%
Withdrawals due to TEAEs	0 0%

11. Secondary Outcome

Title	Number of Participants With Laboratory Test Abnormalities
Description	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).
Time Frame	Screening, Day 0, and Day 7

Outcome Measure Data

Analysis Population Description

The 2 participants who were enrolled and completed the study at the time of study termination were included in all analyses.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Measure Participants	2
Number [participants]	1 50%

12. Secondary Outcome

Title	Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria
Description	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.
Time Frame	Screening, Day 0, and Day 7

Outcome Measure Data

Analysis Population Description

The 2 participants who were enrolled and completed the study at the time of study termination were included in all analyses.

Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
Measure Participants	2
Number [participants]	0 0%

Adverse Events

Time Frame	Screening through to and including 28 calendar days after the last administration of the investigational product.
Adverse Event Reporting Description	All treated participants were analyzed for AEs. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Sulfasalazine in Juvenile Idiopathic Arthritis
Arm/Group Description	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.
All Cause Mortality
	Sulfasalazine in Juvenile Idiopathic Arthritis
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sulfasalazine in Juvenile Idiopathic Arthritis
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Sulfasalazine in Juvenile Idiopathic Arthritis
	Affected / at Risk (%)	# Events
Total	0/2 (0%)

Limitations/Caveats

The study was terminated prematurely and only 2 participants were enrolled and completed the study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.