The purpose of this study is to evaluate the pharmacokinetic (PK) and safety of an age-appropriate tofacitinib Modified Release (MR) formulation with varying level of enteric coating. The effect of food on the PK of age-appropriate tofacitinib MR formulation with the lowest and higher levels of enteric coating will also be assessed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Single oral 10 mg multi particulate dose of dose of tofacitinib MR with different levels of enteric coating (MR E1, MR E2, and MR E3) in the fasted state. Additionally, the lowest and highest enteric coating levels will also be evaluated in the fed state. Treatment F: a 10 mg oral dose of tofacitinib IR solution
New Haven Clinical Research Unit
New Haven, Connecticut, United States
Primary outcome: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] (AUCinf )
Area Under the Curve From Time Zero to Extrapolated Infinite Time \[AUC (0 - ∞)\]
Time frame: 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) of Modified Release (MR) formulation compared to Immediate Release (IR) solution
Time frame: 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose
Maximum Observed Plasma Concentration (Cmax)
Maximum (or peak) plasma concentration of MR formulation compared to IR solution
Time frame: predose, 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Maximum time to peak plasma concentration of MR formulation compared to IR solution
Time frame: predose, 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
The incidence of all-causality TEAEs is summarized by System Organ Class (SOC) and MedDRA preferred term Treatment-Emergent Adverse Events (Treatment Related) For each AE, the investigator will pursue and obtain information adequate both to determine the outcome of the AE and to assess whether it met the criteria for classification as a serious adverse event (SAE)
Time frame: Through study completion, approximately 3 months
Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Leading to Discontinuation
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Discontinuations from the study or study treatment due to AEs, temporary discontinuations or dose reductions due to AEs reported during the study
Time frame: Through study completion, approximately 3 months
Number of Participants With Clinically Significan Change from Baseline in Physical Examination Findings
Full Physical examination includes examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. A limited or abbreviated physical examination assesses the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings are considered to be clinically significant based on investigator's assesment.
Time frame: Through study completion, approximately 3 months
Number of Participants with Clinically Significant Change from Baseline in Vital Signs
The following parameters will be analyzed for examination of vital signs: oral temperature, supine blood pressure, pulse rate.
Time frame: Through study completion, approximately 3 months
Number of Participants with Clinically Significant Change in the QTC interval from Baseline in 12-lead ECGs
Criteria for potential clinical concern in ECG parameters: maximum corrected QT interval (QTc) from baseline is greater than or equal in range of 45 millisecond (msec); or an absolute QTc value of greater than or equal in range of 500 msec in any scheduled ECG.
Time frame: Through study completion, approximately 3 months
Number of Participants with Clinically Significant Laboratory Abnormalities
The following parameters will be analyzed for laboratory examination: hematology, chemistry, urinalysis, microsopy \[only if urine dipstick is positive for blood, protein, nitrites or leukocyte esterase\]; other \[only at screening\] serum follicle stimulating hormone ) for female subjects only who are amenorrheic for at least 12 consecutive months), urine drug testing hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, HIV, QuantiFERON Gold test. Clinical significance of laboratory parameters will be determined at the investigator's discretion.
Time frame: Through study completion, approximately 3 months