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

Pfizer

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: tofacitinib MR 11 mg; Drug: tofacitinib IR 5 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04403776

A3921213

Details and patient eligibility

About

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.

Enrollment: 26 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

Treatment A, separated washout phase, followed Treatment B.

Experimental group

Description:

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.

Treatment:

Drug: tofacitinib IR 5 mg

Drug: tofacitinib MR 11 mg

Treatment B, separated washout phase, followed Treatment A.

Experimental group

Description:

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.

Treatment:

Drug: tofacitinib IR 5 mg

Drug: tofacitinib MR 11 mg