Clinical trial NCT04338711: A Study In Adult Healthy Volunteers To Asses Once Daily (QD) Dosing With The Selected Age-Appropriate Modified Release (MR) Formulations
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-04-08
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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:

  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.

Primary outcomes:
measure: Primary outcome: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] (AUCinf )
timeFrame: 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: predose, 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: predose, 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose
Secondary outcomes:
measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Through study completion, approximately 3 months
measure: Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Leading to Discontinuation
timeFrame: Through study completion, approximately 3 months
measure: Number of Participants With Clinically Significan Change from Baseline in Physical Examination Findings
timeFrame: Through study completion, approximately 3 months
measure: Number of Participants with Clinically Significant Change from Baseline in Vital Signs
timeFrame: Through study completion, approximately 3 months
measure: Number of Participants with Clinically Significant Change in the QTC interval from Baseline in 12-lead ECGs
timeFrame: Through study completion, approximately 3 months
measure: Number of Participants with Clinically Significant Laboratory Abnormalities
timeFrame: Through study completion, approximately 3 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: