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

NCT04338711 | Completed Phase 1 FDA Drug

• 1 other identifier: A3921262
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Primary outcome: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] (AUCinf )

  Area Under the Curve From Time Zero to Extrapolated Infinite Time \[AUC (0 - ∞)\]

  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 Last Quantifiable Concentration (AUClast)

  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

  0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose

• Maximum Observed Plasma Concentration (Cmax)

  Maximum (or peak) plasma concentration of MR formulation compared to IR solution

  predose, 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  Maximum time to peak plasma concentration of MR formulation compared to IR solution

  predose, 0.5, 1, 2, 3, 4, 5, 6, 9, 21, 24, 36, and 48 hours post dose

Secondary Outcomes (6)

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  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

Study Arms (6)

Treatment A

EXPERIMENTAL

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

Drug: tofacitinib modified release (MR)

Treatment B

EXPERIMENTAL

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

Drug: tofacitinib modified release (MR)

Treatment C

EXPERIMENTAL

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

Drug: tofacitinib modified release (MR)

Treatment D

EXPERIMENTAL

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

Drug: tofacitinib modified release (MR)

Treatment E

EXPERIMENTAL

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

Drug: tofacitinib modified release (MR)

Treatment F

ACTIVE COMPARATOR

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

Drug: tofacitinib modified release (MR)

Interventions

tofacitinib modified release (MR) DRUG

Single oral 10 mg multi particulate dose of dose of tofacitinib MR with different levels of enteric coating (MR E1, MR E2, and MR E3) in the fasted state. Additionally, the lowest and highest enteric coating levels will also be evaluated in the fed state. Treatment F: a 10 mg oral dose of tofacitinib IR solution

Treatment A; Treatment B; Treatment C; Treatment D; Treatment E; Treatment F

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2020
• First Posted: April 8, 2020
• Study Start: June 17, 2020
• Primary Completion: September 15, 2020
• Study Completion: September 15, 2020
• Last Updated: October 29, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)