A Study to Demonstrate the Equivalence of the Tofacitinib Oral Solution to the Tablet Formulation in Healthy Participants.

Study Overview
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Brief Summary
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This is a Phase 1, randomized, open label, 2 period, 2 sequence, cross over, single dose study to evaluate the AUC equivalence, and safety of tofacitinib 5 mL oral solution (1 mg/mL) and 5 mg tablet in healthy participants. Participants will be randomized to 1 of the 2 treatment sequences. A total of approximately 12 healthy male and/or female (non-childbearing potential) participants will be enrolled in the study so that approximately 6 participants will be enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods. In both sequences, participants will remain in the CRU for a total of 5 days and 4 nights (including Period 1 and Period 2).

Official Title
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A PHASE 1, RANDOMIZED, OPEN LABEL, 2 PERIOD, CROSS OVER, SINGLE DOSE STUDY TO DEMONSTRATE THE AREA UNDER THE CURVE EQUIVALENCE BETWEEN TOFACITINIB ORAL SOLUTION FORMULATION AND TABLET FORMULATION UNDER FASTED CONDITION IN HEALTHY PARTICIPANTS

Conditions
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Healthy

Intervention / Treatment
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* Drug: Tofacitinib tablet
* Drug: Tofacitinib Oral Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants of non childbearing potential must be 18 to 55 years of age, inclusive, at the time of signing the informed consent document (ICD). Male and female participants of non-childbearing potential who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, blood pressure (BP), pulse rate, oral temperature, and 12 lead electrocardiogram (ECG). Body mass index (BMI) of 17.5 to 30.5 kg/m^2; and a total body weight greater than 50 kg (110 lb). Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic (including alcoholic liver disease, nonalcoholic steatohepatitis (NASH), autoimmune hepatitis, and hereditary liver diseases), psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Clinically significant infections within the past 3 months prior to the baseline visit (for example, those requiring hospitalization or parenteral antibiotics, or as judged by the investigator), evidence of any infection within the past 7 days prior to the baseline visit, history of disseminated herpes simplex infection or recurrent (>1 episode) herpes zoster or disseminated herpes zoster. Any condition possibly affecting drug absorption (eg, gastrectomy). History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed. Malignancy or 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. A positive urine drug test.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Single dose of 5 mL tofacitinib oral solution on Day 1 of Period 1 and Singe dose of 5 mg tofacitinib tablet on Day 1 of Period 2 | Drug: Tofacitinib tablet<br>* Single dose of tofacitinib 5 mg tablet<br>Drug: Tofacitinib Oral Solution<br>* Single 5 mL dose of tofacitinib oral solution (1 mg/mL)<br>|
| Experimental: Arm 2<br>Single dose of 5 mg tofacitinib tablet on Day 1 of Period 1 and Singe dose of 5 mL tofacitinib oral solution on Day 1 of Period 2 | Drug: Tofacitinib tablet<br>* Single dose of tofacitinib 5 mg tablet<br>Drug: Tofacitinib Oral Solution<br>* Single 5 mL dose of tofacitinib oral solution (1 mg/mL)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCinf for tofacitinib oral solution and tofacitinib tablet | Area under the curve from time zero to extrapolated infinite time for both oral solution and tofacitinib. | 24 hrs after study drug administration in Period 1 and Period 2 | 
| AUClast for tofacitinib oral solution and tofacitinib tablet | Area under the plasma concentration time curve from 0 to time of the last measurement of both the tofacitinib oral solution and tofacitinib tablet. | 24 hrs after study drug administration in Period 1 and Period 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax for tofacitinib oral solution and tofacitinib tablet | Maximum observed plasma concentration for tofacitinib oral solution and tofacitinib tablet | 24 hrs after study drug administration in Period 1 and Period 2 | 
| Number of subjects with adverse events (AEs). | Number of subjects with adverse events (AEs). | Screening to up to 28-35 days after the last dose of study medication in Period 2. | 
| Number of subjects with laboratory tests findings of potential clinical importance | Number of subjects with laboratory tests findings of potential clinical importance | Screening through Day 2 of Period 2 | 
| Number of subjects with clinically significant abnormal vital signs | Number of subjects with clinically significant abnormal vital signs | Screening through Day 2 of Period 2 | 
| Number of subjects with clinically significant physical examination findings | Number of subjects with clinically significant physical examination findings. | Screening to Day 2 of Period 2 |