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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04403776
• Other study ID #: A3921213
• Status: Completed
• Phase: Phase 1
• Start date: December 3, 2018
• Est. completion date: February 12, 2019

Study information

• Verified date: May 2020
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: February 12, 2019
• Est. primary completion date: February 12, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• tofacitinib MR 11 mg
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.
• tofacitinib IR 5 mg
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.

Locations

Country	Name	City	State
China	Shuguang Hospital Affiliated to Shanghai University of TCM/Phase I Unit	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration time profile from time zero extrapolated to infinite time (AUCinf)		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.
Primary	Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration (AUClast)		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.
Primary	Area under the concentration time profile for the 24 hour period (AUC24)		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	Single-dose PK: maximum observed concentration (Cmax)		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.
Secondary	Single-dose PK: time for Cmax (Tmax)		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.
Secondary	Single-dose PK: terminal half-life (t1/2)		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.
Secondary	Single-dose PK: area under the plasma concentration-time profile from time 0 to tau (AUCtau)		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.
Secondary	Steady-state PK: Cmax		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	Steady-state PK: lowest concentration observed (Cmin)		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	Steady-state PK: average concentration (Cav)		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	Steady-state PK: Tmax		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	Steady-state PK: concentration at 24 hours (C24)		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	Steady-state PK: peak to trough ratio (PTR)		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	Steady-state PK: peak to trough fluctuation (PTF)		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	Steady-state PK: peak to trough swing (PTS)		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	Steady-state PK: observed accumulation ratio for AUC (Rac)		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	Steady-state PK: observed accumulation ratio for Cmax (Rac,Cmax)		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	Number (%) of subjects with treatment-emergent adverse events	ECG, Clinical Laboratories, Vitals Signs and Physical Exams will be used as a safety measure to detect any AEs.	approximately 18 days

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