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

NCT01513902 | Completed Phase 1 Results

• 2 other identifiers: A39211032011-004914-40
• Study Type: interventional
• Target: 26
• Locations: 4 countries
• Sites: 10

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).

Conditions

Juvenile Idiopathic Arthritis

Keywords

Arthritis; Pediatric; Tofacitinib; JIA

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (6)

• 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)

  Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose

• Plasma Decay Half-Life (t1/2)

  Day 5: Pre-dose, 0.5, 1, 2, 4, 8 hours post dose

Study Arms (3)

Cohort 1

EXPERIMENTAL

Ages 12 to less than 18

Drug: CP-690,550

Cohort 2

EXPERIMENTAL

Ages 6 to less than 12

Drug: CP-690,550

Corhort 3

EXPERIMENTAL

Ages 2 to less than 6

Drug: CP-690,550

Interventions

CP-690,550 DRUG

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

Also known as: Tofacitinib

Cohort 1

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (10)

Explorer Clinic, University of Minnesota Children's Hospital

Minneapolis, Minnesota, 55454, United States

Location

Clinical and Translational Science Institute Masonic Clinical Research Unit (Administration Only)

Minneapolis, Minnesota, 55455, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Randall Children's Hospital at Legacy Emanuel

Portland, Oregon, 97227, United States

Location

PRI - Pediatric Rheumatology Research Institute GmbH

Bad Bramstedt, 24576, Germany

Location

Hamburger Zentrum fuer Kinder-und Jugendrheumatologie SchoenKlinik Hamburg Eilbek

Hamburg, 22081, Germany

Location

Asklepios Klinik Sankt Augustin Gmbh

Sankt Augustin, 53757, Germany

Location

Wojewodzki Specjalistyczny Szpital Dzieciecy im. Sw. Ludwika w Krakowie

Krakow, 31-503, Poland

Location

Klinika Kardiologii i Reumatologii Dzieciecej

Lodz, 91-738, Poland

Location

Narodny ustav reumatickych chorob

Piešťany, 921 12, Slovakia

Location

Related Publications (2)

• Chang C, Vong C, Wang X, Hazra A, Diehl A, Nicholas T, Mukherjee A. Tofacitinib pharmacokinetics in children and adolescents with juvenile idiopathic arthritis. CPT Pharmacometrics Syst Pharmacol. 2024 Apr;13(4):599-611. doi: 10.1002/psp4.13104. Epub 2024 Jan 31.

  PMID: 38298058 DERIVED

• 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.

  PMID: 29282090 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Arthritis, Juvenile; Arthritis

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1--800--718--1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2012
• First Posted: January 20, 2012
• Study Start: March 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: July 4, 2016
• Results First Posted: July 4, 2016

Record last verified: 2016-05

Locations

DE (3); US (4); SL (1); PL (2)