Pharmacokinetics Of CP-690,550 In Pediatric Patients With Juvenile Idiopathic Arthritis (JIA)

Study Overview
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Brief Summary
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Phase 1 study to describe pharmacokinetics of CP-690,550 in pediatric patients 2 to less than 18 years of age with Juvenile Idiopathic Rheumatoid Arthritis (JIA).

Detailed Description
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This is an open-label, non-randomized, multi-center, oral CP-690,550, multiple-dose (twice daily for 5 days [except Day 5 when only morning dose will be given]) study in pediatric subjects with JIA aged from 2 to less than 18 years. Baseline visit will occur within 1 month of the completion of the Screening Visit. The study will consist of three cohorts based on the age of the subjects, Cohort 3: 2 to less than 6 years, Cohort 2: 6 to less than 12 years and Cohort 1: 12 to less than 18 years. In each cohort, at least 8 pediatric subjects with JIA will participate in the study ensuring a total number of at least 24 pediatric evaluable subjects completing the PK period.

Official Title
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An Open-label Multiple Dose Study To Evaluate The Pharmacokinetics, Safety And Tolerability Of CP-690,550 In Pediatric Patients From 2 To Less Than 18 Years Of Age With Juvenile Idiopathic Arthritis (JIA)

Conditions
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Juvenile Idiopathic Arthritis

Intervention / Treatment
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* Drug: CP-690,550
* Drug: CP-690,550
* Drug: CP-690,550


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric patients with JIA aged from 2 to less than 18 years with active JIA (extended oligoarthritis, polyarthritis rheumatoid factor positive or negative, psoriatic arthritis, enthesitis related arthritis), in 5 or more joints (using American College Rheumatology definition of active joint) at the time of the first study drug administration. For subjects receiving MTX treatment, minimum duration of therapy is 4 months and dose stable for at least 6 weeks prior to first dose of study drug. MTX may be administered either orally or parenterally at doses not to exceed 20 mg/wk or 15 mg/m2/week. A negative QuantiFERON-TB Gold In-Tube test performed within the 3 months prior to screening. A negative PPD test can be substituted for the QuantiFERON-TB Gold In-Tube test only if the central laboratory is unable to perform the test or cannot determine the results to be positive or negative and the Pfizer medical monitor approves it, on a case-by-case basis. Exclusion Criteria: Systemic JIA, persistent oligoarthritis, undifferentiated arthritis. Current or recent history of uncontrolled clinically significant renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, or neurological disease. History of any other rheumatic autoimmune disease. Infections: Latent or active TB or any history of previous TB. Chronic infections. Any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within the 6 months prior to the first dose of study drug. Any treated infections within 2 weeks of Baseline visit. A subject known to be infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus. History of infected joint prosthesis with prosthesis still in situ. History of recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex. The biologic agents and DMARDs are disallowed at any time during this study. If a subject needs to be treated with one of these agents, the subject should be discontinued from the study. Subjects who have been vaccinated with live or attenuated vaccines within the 6 weeks prior to the first dose of study medication or is to be vaccinated with these vaccines at any time during treatment or within 6 weeks following discontinuation of study drug. Subjects with a malignancy or with a history of malignancy with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.

Ages Eligible for Study
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Minimum Age: 2 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Ages 12 to less than 18 | Drug: CP-690,550<br>* CP-690,550 will be administered orally twice daily according to the dosing regimen provided below. Oral solution will be used for children weighing <40 kg. Oral tablets will be used for children weighing ≥40 kg. Children aged 12 to less than 18 years who are unable to swallow tablets will have the option of taking oral solution. Body Weight (kg) Dose (mg) Volume (mL) 5-11 1 1; 12-18 1.5 1.5; 19-24 2 2; 25-31 2.5 2.5; 32-39 3 3; ≥40 5 5<br>* Other names: Tofacitinib;|
| Experimental: Cohort 2<br>Ages 6 to less than 12 | Drug: CP-690,550<br>* CP-690,550 will be administered orally twice daily according to the dosing regimen provided below. Oral solution will be used for children weighing <40 kg. Oral tablets will be used for children weighing ≥40 kg. Children less than 12 years of age with a body weight of ≥40 kg will have the option of taking oral solution or tablets. Body Weight (kg) Dose (mg) Volume (mL) 5-11 1 1; 12-18 1.5 1.5; 19-24 2 2; 25-31 2.5 2.5; 32-39 3 3; ≥40 5 5<br>* Other names: Tofacitinib;|
| Experimental: Corhort 3<br>Ages 2 to less than 6 | Drug: CP-690,550<br>* CP-690,550 will be administered orally twice daily according to the dosing regimen provided below. Children with a body weight ≥30 kg will have the option of taking oral solution or tablets, and children weighing <30 kg will be dosed with the oral solution. Body Weight (kg) Dose (mg) Volume (mL) 5-6 1 1; 7-9 1.5 1.5; 10-12 2 2; 21-15 2.5 2.5; 16-19 3 3; 20-22 3.5 3.5; 23-26 4 4; 27-29 4.5 4.5; ≥30 5 5<br>* Other names: Tofacitinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apparent Oral Clearance (CL/F) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is also influenced by the fraction of the dose absorbed. Clearance was estimated by non compartmental analysis (NCA) of PK data. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. It was calculated by dividing the given oral dose by AUCtau. AUCtau is the area under the plasma concentration time-curve from time zero to end of dosing interval. | Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs) All Causalities | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (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. Treatment emergent AEs included both serious and non-serious AEs. | Baseline up to 28 days after the last dose of study drug (Day 5) | 
| Number of Participants With Laboratory Test Abnormalities | Participants with laboratory test abnormalities of potential clinical concern without regard to baseline abnormality were reported. Criteria: Hematology(hemoglobin,hematocrit,red blood cell[RBC] count:<0.8*lower limit of normal [LLN], platelets:<0.5*LLN/greater than [>]1.75*upper limit of normal[ULN], white blood cell [WBC] count:<0.6*LLN></0>1.5*ULN, lymphocytes, total neutrophils:<0.8*LLN or >1.2*ULN, basophils, eosinophil, monocytes:>1.2*ULN); Liver Function (total bilirubin: >1.5*ULN, aspartate aminotransferase,alanine aminotransferase, alkaline phosphatase:>3.0*ULN, total protein, albumin:<0.8*LLN or >1.2*ULN);Renal Function (blood urea nitrogen, creatinine:>1.3*ULN, uric acid:>1.2*ULN); Electrolytes (sodium:<0.95*LLN or >1.05*ULN,potassium,chloride,calcium,bicarbonate:<0.9*LLN or >1.1*ULN);Clinical chemistry (glucose <0.6*LLN or >1.5*ULN, creatine kinase:>3.0*ULN); Urinalysis (Urine WBC and RBC: greater than or equal to [>=] 6/High Power Field [HPF]). | Baseline up to Day 5 | 
| Number of Participants With Clinically Significant Vital Signs Abnormalities | Criteria for vital signs of potentially clinical concern included supine/sitting pulse rate of <40 beats per minute (bpm) or >120 bpm, standing pulse rate of <40 bpm or >140 bpm, systolic blood pressure of >=30 millimeters of mercury (mmHg) change from baseline and systolic blood pressure <90 mmHg, diastolic blood pressure >=20 mmHg change from baseline and diastolic blood pressure <50 mm Hg. | Baseline up to Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) |  | Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) |  | Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose | 
| Apparent Volume of Distribution (Vz/F) | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose | 
| Taste Assessment | Participants were evaluated for taste assessment using a 5 categories questionnaire. Participants were asked to answer one of the following to describe the taste of oral solution of tofacitinib: Dislike very much, dislike a little, not sure, like a little, or like very much. The taste assessment was only performed for participants who received the oral solution. Number of participants within each category are reported. | Day 1, Day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arthritis, Pediatric, Tofacitinib, JIA