- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04403776
PK and Bioavailability Comparison of Tofacitinib Between a Modified Release and The Immediate Release Formulation
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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Shanghai, China, 201203
- Shuguang Hospital Affiliated to Shanghai University of TCM/Phase I Unit
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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 |
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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.
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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.
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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.
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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.
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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.
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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.
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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)
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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)
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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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)
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Number (%) of subjects with treatment-emergent adverse events
Time Frame: approximately 18 days
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ECG, Clinical Laboratories, Vitals Signs and Physical Exams will be used as a safety measure to detect any AEs.
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approximately 18 days
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- A3921213
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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