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

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

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).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tofacitinib tablet; Drug: Tofacitinib Oral Solution

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 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; Single dose of tofacitinib 5 mg tablet; Drug: Tofacitinib Oral Solution; Single 5 mL dose of tofacitinib oral solution (1 mg/mL)
Experimental: Arm 2; 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; Single dose of tofacitinib 5 mg tablet; Drug: Tofacitinib Oral Solution; Single 5 mL dose of tofacitinib oral solution (1 mg/mL)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2019
• Primary Completion (Actual): December 12, 2019
• Study Completion (Actual): December 12, 2019

Study Registration Dates

• First Submitted: September 30, 2019
• First Submitted That Met QC Criteria: September 30, 2019
• First Posted (Actual): October 1, 2019

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 8, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: A3921354

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No