Back to resultsPharmacokinetics Of CP-690,550 In Pediatric Patients With Juvenile Idiopathic Arthritis (JIA)
Primary Purpose
Juvenile Idiopathic Arthritis
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CP-690,550
CP-690,550
CP-690,550
Sponsored by
About this trial
This is an interventional basic science trial for Juvenile Idiopathic Arthritis focused on measuring Arthritis, Pediatric, Tofacitinib, JIA
Eligibility Criteria
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.
Sites / Locations
- Explorer Clinic, University of Minnesota Children's Hospital
- Clinical and Translational Science Institute Masonic Clinical Research Unit (Administration Only)
- Cincinnati Children's Hospital Medical Center
- Randall Children's Hospital at Legacy Emanuel
- PRI - Pediatric Rheumatology Research Institute GmbH
- Hamburger Zentrum fuer Kinder-und Jugendrheumatologie SchoenKlinik Hamburg Eilbek
- Asklepios Klinik Sankt Augustin Gmbh
- Wojewodzki Specjalistyczny Szpital Dzieciecy im. Sw. Ludwika w Krakowie
- Klinika Kardiologii i Reumatologii Dzieciecej
- Narodny ustav reumatickych chorob
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Corhort 3
Arm Description
Ages 12 to less than 18
Ages 6 to less than 12
Ages 2 to less than 6
Outcomes
Primary Outcome Measures
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.
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.
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]).
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.
Secondary Outcome Measures
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Maximum Observed Plasma Concentration (Cmax)
Time to Reach Maximum Observed Plasma Concentration (Tmax)
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.
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01513902
Brief Title
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
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Juvenile Idiopathic Arthritis
Keywords
Arthritis, Pediatric, Tofacitinib, JIA
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Ages 12 to less than 18
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Ages 6 to less than 12
Arm Title
Corhort 3
Arm Type
Experimental
Arm Description
Ages 2 to less than 6
Intervention Type
Drug
Intervention Name(s)
CP-690,550
Other Intervention Name(s)
Tofacitinib
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
CP-690,550
Other Intervention Name(s)
Tofacitinib
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
CP-690,550
Other Intervention Name(s)
Tofacitinib
Intervention Description
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
Primary Outcome Measure Information:
Title
Apparent Oral Clearance (CL/F)
Description
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.
Time Frame
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) All Causalities
Description
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.
Time Frame
Baseline up to 28 days after the last dose of study drug (Day 5)
Title
Number of Participants With Laboratory Test Abnormalities
Description
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]).
Time Frame
Baseline up to Day 5
Title
Number of Participants With Clinically Significant Vital Signs Abnormalities
Description
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.
Time Frame
Baseline up to Day 5
Secondary Outcome Measure Information:
Title
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
Title
Maximum Observed Plasma Concentration (Cmax)
Time Frame
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
Title
Apparent Volume of Distribution (Vz/F)
Description
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.
Time Frame
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
Title
Plasma Decay Half-Life (t1/2)
Description
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame
Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose
Title
Taste Assessment
Description
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.
Time Frame
Day 1, Day 5
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Explorer Clinic, University of Minnesota Children's Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55454
Country
United States
Facility Name
Clinical and Translational Science Institute Masonic Clinical Research Unit (Administration Only)
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Randall Children's Hospital at Legacy Emanuel
City
Portland
State/Province
Oregon
ZIP/Postal Code
97227
Country
United States
Facility Name
PRI - Pediatric Rheumatology Research Institute GmbH
City
Bad Bramstedt
ZIP/Postal Code
24576
Country
Germany
Facility Name
Hamburger Zentrum fuer Kinder-und Jugendrheumatologie SchoenKlinik Hamburg Eilbek
City
Hamburg
ZIP/Postal Code
22081
Country
Germany
Facility Name
Asklepios Klinik Sankt Augustin Gmbh
City
St. Augustin
ZIP/Postal Code
53757
Country
Germany
Facility Name
Wojewodzki Specjalistyczny Szpital Dzieciecy im. Sw. Ludwika w Krakowie
City
Krakow
ZIP/Postal Code
31-503
Country
Poland
Facility Name
Klinika Kardiologii i Reumatologii Dzieciecej
City
Lodz
ZIP/Postal Code
91-738
Country
Poland
Facility Name
Narodny ustav reumatickych chorob
City
Piestany
ZIP/Postal Code
921 12
Country
Slovakia
12. IPD Sharing Statement
Citations:
PubMed Identifier
29282090
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.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A3921103&StudyName=Pharmacokinetics%20Of%20CP-690%2C550%20In%20Pediatric%20Patients%20With%20Juvenile%20Idiopathic%20Arthritis%20%28JIA%29
Description
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Pharmacokinetics Of CP-690,550 In Pediatric Patients With Juvenile Idiopathic Arthritis (JIA)
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