PK and Bioavailability Comparison of Tofacitinib Between a Modified Release and The Immediate Release Formulation

May 22, 2020 updated by: Pfizer

A Phase 1, Randomized, Open-Label, 2-Way Crossover Study To Evaluate Single Dose And Steady State PK And Bioavailability Between A Modified Release Tofacitinib (11 Mg QD) And The Immediate Release Tofacitinib (5 Mg BID) In Chinese Healthy Subjects

A study to characterize the single-dose and steady-state pharmacokinetics of tofacitinib Modified Release (MR) formulation as well as to compare the extent of absorption of the MR 11 mg formulation (once daily) to that of the Immediate Release (IR) 5 mg formulation (twice daily) of tofacitinib in Chinese healthy subjects under fasted conditions.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Shanghai, China, 201203
        • Shuguang Hospital Affiliated to Shanghai University of TCM/Phase I Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects must be of Chinese ethnicity (individuals currently residing in mainland China who were born in China and have both parents of Chinese descent).
  • Healthy male and/or female subjects of non-childbearing potential
  • Female subjects of non-childbearing potential must meet at least one of the following criteria:
  • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state;
  • Have undergone a documented hysterectomy and/or bilateral oophorectomy;
  • Have medically confirmed ovarian failure.
  • Body Mass Index (BMI) of 19.0 to 26.0 kg/m2; and a total body weight >50 kg (110 lbs).

Exclusion Criteria:

Subjects presenting with any of the following will not be included in the study:

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, 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 first dosing (eg, those requiring hospitalization or parenteral antibiotics, or as judged by the Investigator), evidence of any infection within the past 7 days prior to first dosing, history of disseminated herpes simplex infection or recurrent (>1 episode) or disseminated herpes zoster.
  • Any condition possibly affecting drug absorption (eg, gastrectomy, colon resection, etc.).
  • Use of CYP3A4 inhibitors (eg, ketoconazole, ciprofloxacin, diltiazem) or inducers (eg, phenytoin, carbamazepine, rifampin) within 14 days or 5 half lives (whichever is longer) prior to dosing.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment A, separated washout phase, followed Treatment B.

Treatment A:

Single oral dose of tofacitinib MR 11mg, administered as 1xMR 11mg tablet, in a fasting state on Day 1 followed by once daily dosing (QD) on Days 3, 4, 5, 6 and 7.

washout phase: no later than 72 hours

Treatment B:

Two separate oral doses (12 hours apart) of tofacitinib IR 5mg, administered one in the morning in a fasting state and one in the evening at least 2 hours after dinner on Day 1 followed by 5 mg IR every 12 hours on Days 3, 4, 5, 6 and 7.

Single oral dose of tofacitinib MR 11 mg, administered as 1 x MR 11 mg tablet, in a fasting state on Day 1 followed by once daily dosing (QD) on Days 3, 4, 5, 6 and 7.
Two separate oral doses (12 hours apart) of tofacitinib IR 5 mg, administered one in the morning in a fasting state and one in the evening at least 2 hours after dinner on Day 1 followed by 5 mg IR every 12 hours on Days 3, 4, 5, 6 and 7.
EXPERIMENTAL: Treatment B, separated washout phase, followed Treatment A.

Treatment A:

Single oral dose of tofacitinib MR 11mg, administered as 1xMR 11mg tablet, in a fasting state on Day 1 followed by once daily dosing (QD) on Days 3, 4, 5, 6 and 7.

Washout phase: no later than 72 hours

Treatment B:

Two separate oral doses (12 hours apart) of tofacitinib IR 5mg, administered one in the morning in a fasting state and one in the evening at least 2 hours after dinner on Day 1 followed by 5 mg IR every 12 hours on Days 3, 4, 5, 6 and 7.

Single oral dose of tofacitinib MR 11 mg, administered as 1 x MR 11 mg tablet, in a fasting state on Day 1 followed by once daily dosing (QD) on Days 3, 4, 5, 6 and 7.
Two separate oral doses (12 hours apart) of tofacitinib IR 5 mg, administered one in the morning in a fasting state and one in the evening at least 2 hours after dinner on Day 1 followed by 5 mg IR every 12 hours on Days 3, 4, 5, 6 and 7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Area under the plasma concentration time profile from time zero extrapolated to infinite time (AUCinf)
Time Frame: Plasma PK samples will be collected pre dose and after the Day 1 AM dose of MR and IR treatments and the PM dose of the IR treatment.
Plasma PK samples will be collected pre dose and after the Day 1 AM dose of MR and IR treatments and the PM dose of the IR treatment.
Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration (AUClast)
Time Frame: Plasma PK samples will be collected pre dose and after the Day 1 AM dose of MR and IR treatments and the PM dose of the IR treatment.
Plasma PK samples will be collected pre dose and after the Day 1 AM dose of MR and IR treatments and the PM dose of the IR treatment.
Area under the concentration time profile for the 24 hour period (AUC24)
Time Frame: Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Single-dose PK: maximum observed concentration (Cmax)
Time Frame: Plasma PK samples will be collected pre dose and after the Day 1 AM dose of MR and IR treatments and the PM dose of the IR treatment.
Plasma PK samples will be collected pre dose and after the Day 1 AM dose of MR and IR treatments and the PM dose of the IR treatment.
Single-dose PK: time for Cmax (Tmax)
Time Frame: Plasma PK samples will be collected pre dose and after the Day 1 AM dose of MR and IR treatments and the PM dose of the IR treatment.
Plasma PK samples will be collected pre dose and after the Day 1 AM dose of MR and IR treatments and the PM dose of the IR treatment.
Single-dose PK: terminal half-life (t1/2)
Time Frame: Plasma PK samples will be collected pre dose and after the Day 1 AM dose of MR and IR treatments and the PM dose of the IR treatment.
Plasma PK samples will be collected pre dose and after the Day 1 AM dose of MR and IR treatments and the PM dose of the IR treatment.
Single-dose PK: area under the plasma concentration-time profile from time 0 to tau (AUCtau)
Time Frame: Plasma PK samples will be collected pre dose and after the Day 1 AM dose of MR and IR treatments and the PM dose of the IR treatment.
Plasma PK samples will be collected pre dose and after the Day 1 AM dose of MR and IR treatments and the PM dose of the IR treatment.
Steady-state PK: Cmax
Time Frame: Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Steady-state PK: lowest concentration observed (Cmin)
Time Frame: Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Steady-state PK: average concentration (Cav)
Time Frame: Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Steady-state PK: Tmax
Time Frame: Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Steady-state PK: concentration at 24 hours (C24)
Time Frame: Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Steady-state PK: peak to trough ratio (PTR)
Time Frame: Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Steady-state PK: peak to trough fluctuation (PTF)
Time Frame: Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Steady-state PK: peak to trough swing (PTS)
Time Frame: Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Steady-state PK: observed accumulation ratio for AUC (Rac)
Time Frame: Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Steady-state PK: observed accumulation ratio for Cmax (Rac,Cmax)
Time Frame: Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Blood samples for assessing steady state PK will be collected prior to dosing on Days 5, 6 and 7 and after dosing on Day 7 (up to 24 hours post Day 7 AM dose)
Number (%) of subjects with treatment-emergent adverse events
Time Frame: approximately 18 days
ECG, Clinical Laboratories, Vitals Signs and Physical Exams will be used as a safety measure to detect any AEs.
approximately 18 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 3, 2018

Primary Completion (ACTUAL)

February 12, 2019

Study Completion (ACTUAL)

February 12, 2019

Study Registration Dates

First Submitted

May 4, 2020

First Submitted That Met QC Criteria

May 22, 2020

First Posted (ACTUAL)

May 27, 2020

Study Record Updates

Last Update Posted (ACTUAL)

May 27, 2020

Last Update Submitted That Met QC Criteria

May 22, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • A3921213

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

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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