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

May 24, 2016 updated by: Pfizer

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)

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bad Bramstedt, Germany, 24576
        • PRI - Pediatric Rheumatology Research Institute GmbH
      • Hamburg, Germany, 22081
        • Hamburger Zentrum fuer Kinder-und Jugendrheumatologie SchoenKlinik Hamburg Eilbek
      • St. Augustin, Germany, 53757
        • Asklepios Klinik Sankt Augustin GmbH
  • Poland
      • Krakow, Poland, 31-503
        • Wojewódzki Specjalistyczny Szpital Dziecięcy im. św. Ludwika w Krakowie
      • Lodz, Poland, 91-738
        • Klinika Kardiologii i Reumatologii Dzieciecej
  • Slovakia
      • Piestany, Slovakia, 921 12
        • Narodny ustav reumatickych chorob
  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55454
        • Explorer Clinic, University of Minnesota Children's Hospital
      • Minneapolis, Minnesota, United States, 55455
        • Clinical and Translational Science Institute Masonic Clinical Research Unit (Administration Only)
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
    • Oregon
      • Portland, Oregon, United States, 97227
        • Randall Children's Hospital at Legacy Emanuel

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1
Ages 12 to less than 18
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 Names:
  • 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 Names:
  • 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 Names:
  • Tofacitinib
Experimental: Cohort 2
Ages 6 to less than 12
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 Names:
  • 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 Names:
  • 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 Names:
  • Tofacitinib
Experimental: Corhort 3
Ages 2 to less than 6
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 Names:
  • 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 Names:
  • 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 Names:
  • Tofacitinib

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
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.
Baseline up to 28 days after the last dose of study drug (Day 5)
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]).
Baseline up to Day 5
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.
Baseline up to Day 5

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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
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
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.
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
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.
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
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.
Day 1, Day 5

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 17, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 17, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 20, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 4, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 24, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • A3921103
  • 2011-004914-40 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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