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Pediatr Rheumatol Online J. 2017 Dec 28;15(1):86. doi: 10.1186/s12969-017-0212-y.

Pharmacokinetic and safety profile of tofacitinib in children with polyarticular course juvenile idiopathic arthritis: results of a phase 1, open-label, multicenter study.

Author information

1
Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, PRINTO, Genoa, Italy. nicolaruperto@gaslini.org.
2
Cincinnati Children's Hospital Medical Center, PRCSG, Cincinnati, OH, USA.
3
St Louis Children's Hospital ODS Rheumatology and Neurology, Krakow, Poland.
4
Pediatric Rheumatology Research Institute, Bad Bramstedt, Germany.
5
Randall Children's Hospital, Portland, OR, USA.
6
Hamburger Zentrum für Kinder- und Jugendrheumatologie, Hamburg, Germany.
7
Centre of General Pediatrics and Neonatology, Asklepios Klinik, Sankt Augustin, Germany.
8
Department of Pediatric Rheumatology, Medical University of Lodz, Lodz, Poland.
9
University of Minnesota Masonic Children's Hospital, Minneapolis, MN, USA.
10
Pfizer Inc, Collegeville, PA, USA.
11
Pfizer Inc, Groton, CT, USA.
12
Istituto Giannina Gaslini, Direzione Scientifica, Genoa, Italy.

Abstract

BACKGROUND:

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and a leading cause of childhood disability. The objective of this study was to characterize the PK, safety, and taste acceptability of tofacitinib in patients with JIA.

METHODS:

This Phase 1, open-label, multiple-dose (twice daily [BID] for 5 days) study of tofacitinib in patients with active (≥ 5 joints) polyarticular course JIA was conducted from March 2013-December 2015. Patients were allocated to one of three age-based cohorts: Cohort 1, 12 to < 18 years; Cohort 2, 6 to < 12 years; and Cohort 3, 2 to < 6 years. Tofacitinib was administered according to age and body weight as tablets or oral solution (grape flavor). PK were assessed on Day 5; safety was assessed at screening, Day 1, and Day 5. Taste acceptability of the oral solution was evaluated.

RESULTS:

Twenty-six patients (age range 2-17 years) were enrolled: Cohort 1, N = 8; Cohort 2, N = 9; Cohort 3, N = 9; median tofacitinib doses were 5.0, 2.5, and 3.0 mg BID, respectively. The higher median tofacitinib dose in Cohort 3 versus Cohort 2 reflected implementation of an amended dosing scheme following an interim PK analysis after Cohort 2 recruitment. Geometric mean AUC at steady state (AUCtau) was 156.6 ng•h/mL in Cohort 1, 118.8 ng•h/mL in Cohort 2, and 142.5 ng•h/mL in Cohort 3; Cmax (ng/mL) was 47.0, 41.7, and 66.2, respectively. Ctrough, Cmin, and t1/2 were similar in Cohorts 2 and 3, but higher in Cohort 1. Median time to Cmax (Tmax) was similar between cohorts. Apparent clearance and volume of distribution decreased with decreasing age. Tofacitinib was well tolerated, with no serious adverse events or discontinuations due to adverse events reported. Taste acceptability was confirmed.

CONCLUSIONS:

PK findings from this study in children with polyarticular course JIA established dosing regimens and acceptable taste for use in subsequent studies within the tofacitinib pediatric development program.

TRIAL REGISTRATION:

ClinicalTrials.gov: NCT01513902 .

KEYWORDS:

Dosing; Janus kinase inhibitor; Juvenile idiopathic arthritis; Pediatric; Pharmacokinetics; Safety; Tofacitinib

PMID:
29282090
PMCID:
PMC5745974
DOI:
10.1186/s12969-017-0212-y
[Indexed for MEDLINE]
Free PMC Article

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