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

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ClinicalTrials.gov Identifier: NCT01513902
Recruitment Status : Completed
First Posted : January 20, 2012
Results First Posted : July 4, 2016
Last Update Posted : July 4, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE January 17, 2012
First Posted Date  ICMJE January 20, 2012
Results First Submitted Date  ICMJE May 24, 2016
Results First Posted Date  ICMJE July 4, 2016
Last Update Posted Date July 4, 2016
Study Start Date  ICMJE March 2013
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2016)
  • Apparent Oral Clearance (CL/F) [ Time Frame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose ]
    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.
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) All Causalities [ Time Frame: Baseline up to 28 days after the last dose of study drug (Day 5) ]
    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.
  • Number of Participants With Laboratory Test Abnormalities [ Time Frame: Baseline up to Day 5 ]
    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]).
  • Number of Participants With Clinically Significant Vital Signs Abnormalities [ Time Frame: Baseline up to Day 5 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 17, 2012)
  • Apparent Oral Clearance (CL/F) [ Time Frame: Day 5 predose, 0.5, 1, 2, 4 and 8 hours post morning dose ]
  • Number of participants with adverse events [ Time Frame: Baseline up to Day 5 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2016)
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) [ Time Frame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose ]
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose ]
  • Apparent Volume of Distribution (Vz/F) [ Time Frame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose ]
    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.
  • Plasma Decay Half-Life (t1/2) [ Time Frame: Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Taste Assessment [ Time Frame: Day 1, Day 5 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2012)
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) [ Time Frame: Day 5 predose, 0.5, 1, 2, 4 and 8 hours post morning dose ]
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day 5 predose, 0.5, 1, 2, 4 and 8 hours post morning dos, 0.5, 1, 2, 4 and 8 hours post morning dose ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Day 5 predose, 0.5, 1, 2, 4 and 8 hours post morning dose ]
  • Plasma Decay Half-Life (t1/2) [ Time Frame: Day 5 predose, 0.5, 1, 2, 4 and 8 hours post morning dose ]
  • Taste acceptability assessment questionnaire [ Time Frame: Baseline, Day 5 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics Of CP-690,550 In Pediatric Patients With Juvenile Idiopathic Arthritis (JIA)
Official Title  ICMJE 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)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Juvenile Idiopathic Arthritis
Intervention  ICMJE
  • Drug: CP-690,550
    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
    Other Name: Tofacitinib
  • Drug: CP-690,550
    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
    Other Name: Tofacitinib
  • Drug: CP-690,550
    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
    Other Name: Tofacitinib
Study Arms  ICMJE
  • Experimental: Cohort 1
    Ages 12 to less than 18
    Intervention: Drug: CP-690,550
  • Experimental: Cohort 2
    Ages 6 to less than 12
    Intervention: Drug: CP-690,550
  • Experimental: Corhort 3
    Ages 2 to less than 6
    Intervention: Drug: CP-690,550
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 30, 2016)
26
Original Estimated Enrollment  ICMJE
 (submitted: January 17, 2012)
24
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Poland,   Slovakia,   United States
Removed Location Countries Hungary
 
Administrative Information
NCT Number  ICMJE NCT01513902
Other Study ID Numbers  ICMJE A3921103
2011-004914-40 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP