Clinical trial NCT01513902: Pharmacokinetics Of CP-690,550 In Pediatric Patients With Juvenile Idiopathic Arthritis (JIA)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Juvenile Idiopathic Arthritis
Keywords: Arthritis
Pediatric
Tofacitinib
JIA
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-01-20
Enrollment: 26
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. 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:

1. Systemic JIA, persistent oligoarthritis, undifferentiated arthritis.
2. Current or recent history of uncontrolled clinically significant renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, or neurological disease.
3. History of any other rheumatic autoimmune disease.
4. Infections:

   1. Latent or active TB or any history of previous TB.
   2. Chronic infections.
   3. 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.
   4. Any treated infections within 2 weeks of Baseline visit.
   5. A subject known to be infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus.
   6. History of infected joint prosthesis with prosthesis still in situ.
5. History of recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
6. 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.
7. 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.
8. 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.

Primary outcomes:
measure: Apparent Oral Clearance (CL/F)
timeFrame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) All Causalities
timeFrame: Baseline up to 28 days after the last dose of study drug (Day 5)
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: Baseline up to Day 5
measure: Number of Participants With Clinically Significant Vital Signs Abnormalities
timeFrame: Baseline up to Day 5
Secondary outcomes:
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
timeFrame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
measure: Plasma Decay Half-Life (t1/2)
timeFrame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
measure: Taste Assessment
timeFrame: Day 1, Day 5
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Explorer Clinic, University of Minnesota Children's Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Clinical and Translational Science Institute Masonic Clinical Research Unit (Administration Only)
state: Minnesota
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Randall Children's Hospital at Legacy Emanuel
state: Oregon
city: Bad Bramstedt
country: Germany
facility: PRI - Pediatric Rheumatology Research Institute GmbH
city: Hamburg
country: Germany
facility: Hamburger Zentrum fuer Kinder-und Jugendrheumatologie SchoenKlinik Hamburg Eilbek
city: St. Augustin
country: Germany
facility: Asklepios Klinik Sankt Augustin Gmbh
city: Krakow
country: Poland
facility: Wojewodzki Specjalistyczny Szpital Dzieciecy im. Sw. Ludwika w Krakowie
city: Lodz
country: Poland
facility: Klinika Kardiologii i Reumatologii Dzieciecej
city: Piestany
country: Slovakia
facility: Narodny ustav reumatickych chorob
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Ruperto N, Brunner HI, Zuber Z, Tzaribachev N, Kingsbury DJ, Foeldvari I, Horneff G, Smolewska E, Vehe RK, Hazra A, Wang R, Mebus CA, Alvey C, Lamba M, Krishnaswami S, Stock TC, Wang M, Suehiro R, Martini A, Lovell DJ; Pediatric Rheumatology International Trials Organization (PRINTO); Pediatric Rheumatology Collaborative Study Group (PRCSG). Pharmacokinetic and safety profile of tofacitinib in children with polyarticular course juvenile idiopathic arthritis: results of a phase 1, open-label, multicenter study. Pediatr Rheumatol Online J. 2017 Dec 28;15(1):86. doi: 10.1186/s12969-017-0212-y.