A PHASE 1, RANDOMIZED, OPEN LABEL, PARTIAL CROSSOVER STUDY TO EVALUATE THE PHARMACOKINETICS AND SAFETY OF THREE AGE-APPROPRIATE MODIFIED RELEASE FORMULATIONS AND THE IMMEDIATE RELEASE SOLUTION OF TOFACITINIB IN HEALTHY ADULT VOLUNTEERS
Overview
- Phase
- Phase 1
- Intervention
- tofacitinib modified release (MR)
- Conditions
- Healthy
- Sponsor
- Pfizer
- Enrollment
- 23
- Locations
- 1
- Primary Endpoint
- Primary outcome: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] (AUCinf )
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the pharmacokinetic (PK) and safety of an age-appropriate tofacitinib Modified Release (MR) formulation with varying level of enteric coating. The effect of food on the PK of age-appropriate tofacitinib MR formulation with the lowest and higher levels of enteric coating will also be assessed.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 55 years, inclusive.
- •Female subjects of non-childbearing potential must meet at least 1 of the following criteria:
- •. Achieved postmenopausal status, defined as: cessation of regular menses for at lease 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. All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
- •Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight ˃50 kg (110 lbs) for males and ˃45 kg (99 lbs) for females
- •No evidence of active or latent or inadequately treated infection with Mycobaceterium tuberculosis (TB)
Exclusion Criteria
- •Evidence or history of clinical significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, season allergies at the time of dosing.
- •Clinically significant infections within the past 3 months (for example, those requiring hospitalization or parenteral antibiotics, or as judged by the investigator), evidence of any infection within the past 7 days, history of disseminated herpes simplex infection or recurrent (˃1 episode) herpes zoster or disseminated herpes zoster.
- •Absolute lymphocyte count at Screening or Baseline (Day -1 of Period 1) less than the lower limit of the reference range for the local laboratory (lymphocyte count ˂0.8\* 10˄3).
- •Evidence of hematopoietic disorder or hemoglobin ˂12.5 g/dL for females and ˂13 g/dL for males at Screening or Baseline ((Day -1 of Period 1).
- •Evidence or history of cyclic neutropenia.
- •Personal or family history of hereditary immunodeficiency (eg, severe combined immunodeficiency disorder \[SCID\], Wiskott-Aldrich syndrome, X-linked agammaglobulinemia).
- •Vaccination with live or attenuated vaccines within 6 weeks of dosing, or is to be vaccinated with these vaccines at any time during study treatment or within 6 weeks following discontinuation of dosing.
- •Any condition possibly affecting drug absorption (eg, gastrectomy, colon resection, etc.).
- •History of, or current positive results for any of the following serological tests: human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatits B surface antigen (HepBsAg), Hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb).
- •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.
Arms & Interventions
Treatment A
Single oral 10 mg dose of tofacitinib MR E1 administered in the fasted state.
Intervention: tofacitinib modified release (MR)
Treatment B
Single oral 10 mg dose of tofacitinib MR E2 administered in the fasted state.
Intervention: tofacitinib modified release (MR)
Treatment C
Single oral 10 mg dose of tofacitinib MR E3 administered in the fasted state.
Intervention: tofacitinib modified release (MR)
Treatment D
Single oral 10 mg dose of tofacitinib MR E1 administered in the fed state.
Intervention: tofacitinib modified release (MR)
Treatment E
Single oral 10 mg dose of tofacitinib MR E3 administered in the fed state.
Intervention: tofacitinib modified release (MR)
Treatment F
Single oral 10 mg dose of tofacitinib IR Solution (10 mL of the 1 mg/mL solution) administered in the fasted state.
Intervention: tofacitinib modified release (MR)
Outcomes
Primary Outcomes
Primary outcome: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] (AUCinf )
Time Frame: 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time \[AUC (0 - ∞)\]
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Time Frame: 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) of Modified Release (MR) formulation compared to Immediate Release (IR) solution
Maximum Observed Plasma Concentration (Cmax)
Time Frame: predose, 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose
Maximum (or peak) plasma concentration of MR formulation compared to IR solution
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: predose, 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose
Maximum time to peak plasma concentration of MR formulation compared to IR solution
Secondary Outcomes
- Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Through study completion, approximately 3 months)
- Number of Participants with Clinically Significant Laboratory Abnormalities(Through study completion, approximately 3 months)
- Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Leading to Discontinuation(Through study completion, approximately 3 months)
- Number of Participants With Clinically Significan Change from Baseline in Physical Examination Findings(Through study completion, approximately 3 months)
- Number of Participants with Clinically Significant Change from Baseline in Vital Signs(Through study completion, approximately 3 months)
- Number of Participants with Clinically Significant Change in the QTC interval from Baseline in 12-lead ECGs(Through study completion, approximately 3 months)