A Study In Adult Healthy Volunteers To Asses Once Daily (QD) Dosing With The Selected Age-Appropriate Modified Release (MR) Formulations

Pfizer

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: tofacitinib modified release (MR)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04338711

A3921262

Details and patient eligibility

About

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.

Enrollment: 23 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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:

  1. . 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;
  2. . have undergone a documented hysterectomy and/or bilateral oophorectomy;
  3. . 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.
• Positive urine drug test.
• History of regular alcohol consumption.
• Use of tobacco-or nicotine-containing products in excess of the equivalent of 5 cigarettes per day.
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of the investigational product (whichever is longer).
• Screening supine 12-lead ECG demonstrating a corrected QT (QTc) interval ˃450 msec or a QRS interval ˃120 msec.
• Nursing females or females of childbering potential. Male subjects who are unwilling or unable to use a condom plus a highly effective method of contraception as outline in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
• Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of investigational product. Herbal supplements and hormone replacement therapy must be discontinued at least 28 days prior to the first dose of investigational product.
• 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.
• Consumption of grapefruit or grapefruit-related citrus fruits (eg, Seville oranges, pomelos) or juices within 7 days prior to dosing.
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
• History of sensitivity to heparin or heparing-induced thrombocytopenia.
• History of hypersensitivity to tofacitinib or any of the components of the formulation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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23 participants in 6 patient groups

Treatment A

Experimental group

Description:

Single oral 10 mg dose of tofacitinib MR E1 administered in the fasted state.

Treatment:

Drug: tofacitinib modified release (MR)

Treatment B

Experimental group

Description:

Single oral 10 mg dose of tofacitinib MR E2 administered in the fasted state.

Treatment:

Drug: tofacitinib modified release (MR)

Treatment C

Experimental group

Description:

Single oral 10 mg dose of tofacitinib MR E3 administered in the fasted state.

Treatment:

Drug: tofacitinib modified release (MR)

Treatment D

Experimental group

Description:

Single oral 10 mg dose of tofacitinib MR E1 administered in the fed state.

Treatment:

Drug: tofacitinib modified release (MR)

Treatment E

Experimental group

Description:

Single oral 10 mg dose of tofacitinib MR E3 administered in the fed state.

Treatment:

Drug: tofacitinib modified release (MR)

Treatment F

Active Comparator group

Description:

Single oral 10 mg dose of tofacitinib IR Solution (10 mL of the 1 mg/mL solution) administered in the fasted state.

Treatment:

Drug: tofacitinib modified release (MR)