A Single Dose Study To Test Two Pediatric Forms Of Ritlecitinib Compared With Adult Ritlecitinib In Healthy Adults

Study Overview
=================
Brief Summary
-----------------
A phase I, single dose study to test two forms of pediatric ritlecitinib compared to adult ritlecitinib in healthy adults aged 18-55 years old. Approximately 12 adults will participate for approximately 2.5 months.

Official Title
-----------------
A PHASE 1, RANDOMIZED, OPEN-LABEL, CROSS-OVER, SINGLE DOSE STUDY TO ESTIMATE THE RELATIVE BIOAVAILABILITY OF PEDIATRIC RITLECITINIB (PF-06651600) CAPSULES AND SPRAY CONGEALED BEADS RELATIVE TO ADULT CAPSULES IN HEALTHY ADULT PARTICIPANTS

Conditions
-----------------
Healthy Participants

Intervention / Treatment
-----------------
* Drug: ritlecitinib
* Drug: ritlecitinib
* Drug: ritlecitinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female participants who are healthy as determined by medical evaluation including a detailed medical history, complete (full) physical examination, which includes BP and pulse rate measurement, clinical laboratory tests, and 12-lead ECG. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, dermatological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). Known immunodeficiency disorder, including positive serology for HIV at screening, or a first degree relative with a hereditary immunodeficiency Infection with hepatitis B or hepatitis C viruses. History of any lymphoproliferative disorder Known present or a history of malignancy other than a successfully treated or excised nonmetastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence 1<br>Treatment sequence 1 will receive a single 30 milligrams (mg) ritlecitinib intact adult capsule during the first period, three 10 mg ritlecitinib pediatric capsules during the second period and 30 mg ritlecitinib spray congealed beads in the third period. | Drug: ritlecitinib<br>* 30 mg intact adult capsule<br>Drug: ritlecitinib<br>* 10 mg pediatric capsule<br>Drug: ritlecitinib<br>* 30 mg spray congealed beads<br>|
| Experimental: Treatment Sequence 2<br>Treatment sequence 2 will receive three 10 mg ritlecitinib pediatric capsules during the first period, a single 30 mg intact adult capsule during the second period and 30 mg ritlecitinib spray congealed beads in the third period. | Drug: ritlecitinib<br>* 30 mg intact adult capsule<br>Drug: ritlecitinib<br>* 10 mg pediatric capsule<br>Drug: ritlecitinib<br>* 30 mg spray congealed beads<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for Ritlecitinib | Plasma AUCinf for ritlecitinib is reported. AUCinf was calculated as [AUClast+(Clast*/kel)], where AUClast is the area under the plasma concentration-time profile from time 0 to the time of the Clast, Clast is the last quantifiable concentration, Clast* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, and 24 hours post dose on Day 1 in each period | 
| Maximum Plasma Concentration (Cmax) for Ritlecitinib | Plasma Cmax for ritlecitinib is reported. | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, and 24 hours post dose on Day 1 in each period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Treatment-emergent AEs (TEAEs) = between first dose of study treatment and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A serious AE (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-related AEs and SAEs were determined by the investigator. Severe=an event that prevents normal everyday activities. | Post first dose of study intervention on Period 1 Day 1 up to 35 days post last dose of study intervention on Period 3 Day 1 (maximum of 40 days) | 
| Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality | Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, etc), chemistry (fasting glucose, calcium, sodium, potassium, chloride, total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, uric acid, total protein, albumin, etc), and urinalysis (glucose, protein, blood, ketones, nitrites, leukocyte esterase, etc). Baseline = the last pre-dose measurement before Period 1 Day 1 (ie, first dose of study intervention). Laboratory abnormalities meeting pre-defined criteria are reported for this outcome measure. ULN=upper limit of normal. LLN=lower limit of normal. HPF=high-powered field. mEq=milliequivalent. L=liter. | Baseline up to Period 3 Day 2 (maximum of 7 days) |