A PHASE 1, OPEN-LABEL, RANDOMIZED, SINGLE-DOSE, 4-PERIOD, 4-SEQUENCE, CROSSOVER STUDY TO EVALUATE THE RELATIVE BIOAVAILABILITY OF A MODIFIED-RELEASE FORMULATION OF PF-06865571 RELATIVE TO AN IMMEDIATE-RELEASE FORMULATION UNDER FED CONDITIONS, AND TO EVALUATE THE EFFECT OF FASTING ON THE PHARMACOKINETICS OF THE MODIFIED-RELEASE FORMULATION, IN HEALTHY WESTERN AND JAPANESE PARTICIPANTS
Overview
- Phase
- Phase 1
- Intervention
- PF-06865571 400 mg Immediate Release (IR) in Fed State
- Conditions
- Healthy Participants
- Sponsor
- Pfizer
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Single Dose Maximum Observed Plasma Concentration (Cmax) of PF-06865571 in Healthy Participants
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This study is an open-label, randomized, single-dose, 4-period, 4-sequence, crossover study in a single cohort of approximately 12 healthy adult participants. The purpose of this study is to evaluate the relative bioavailability of a newly developed modified release (MR) tablet formulation of PF-06865571 relative to an immediate release (IR) tablet formulation of PF-06865571 under fed conditions. In addition, this study will also assess the relative bioavailability of the MR formulation under fasted conditions relative to fed conditions, in healthy adult participants. Study results will be used to determine if the new MR formulation may be suitable for use in future clinical studies with PF-06865571. Healthy adult Japanese participants will also be enrolled in this study to support inclusion of Japanese participants in future clinical studies.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female participants of non-childbearing potential and male participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac tests.
- •Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
- •Participants enrolling as Japanese must have 4 biological Japanese grandparents who were born in Japan.
Exclusion Criteria
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
- •Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of investigational product.
- •Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product used in this study (whichever is longer).
- •Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest.
- •Baseline 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline corrected QT (QTc) interval \>450 msec, complete left bundle branch block \[LBBB\], signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third-degree atrioventricular \[AV\] block, or serious bradyarrhythmias or tachyarrhythmias).
- •Participants with any of the following abnormalities in clinical laboratory tests at screening: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥1.25× upper limit of normal (ULN); Total bilirubin level ≥1.5× ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.
Arms & Interventions
Relative Bioavailability
Each participant will receive 400 mg IR, 400 mg MR, and 50 mg MR in the fed state, and 400 mg MR in the fasted state
Intervention: PF-06865571 400 mg Immediate Release (IR) in Fed State
Relative Bioavailability
Each participant will receive 400 mg IR, 400 mg MR, and 50 mg MR in the fed state, and 400 mg MR in the fasted state
Intervention: PF-06865571 50 mg Modified Release (MR) in Fed State
Relative Bioavailability
Each participant will receive 400 mg IR, 400 mg MR, and 50 mg MR in the fed state, and 400 mg MR in the fasted state
Intervention: PF-06865571 400 mg MR in Fed State
Relative Bioavailability
Each participant will receive 400 mg IR, 400 mg MR, and 50 mg MR in the fed state, and 400 mg MR in the fasted state
Intervention: PF-06865571 400 mg MR in Fasted State
Fasted State
Comparison of 400 mg MR in fed and fasted states
Intervention: PF-06865571 400 mg MR in Fed State
Fasted State
Comparison of 400 mg MR in fed and fasted states
Intervention: PF-06865571 400 mg MR in Fasted State
Outcomes
Primary Outcomes
Single Dose Maximum Observed Plasma Concentration (Cmax) of PF-06865571 in Healthy Participants
Time Frame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
All study participants
Single Dose Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06865571 in Healthy Participants
Time Frame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
All study participants
Single Dose Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC(last)] of PF-06865571 in Healthy Participants
Time Frame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
All study participants
Single Dose Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC(0-∞)] of PF-06865571 in Healthy Participants
Time Frame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
All study participants
Secondary Outcomes
- Number of Participants With Clinically Significant Change From Baseline in Vital Signs(Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose)
- Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings(Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose)
- Single Dose Cmax of PF-06865571 in Healthy Japanese Participants(Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose)
- Single Dose Tmax of PF-06865571 in Healthy Japanese Participants(Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose)
- Single Dose AUC(last) of PF-06865571 in Healthy Japanese Participants(Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose)
- Single Dose AUC(0-∞) of PF-06865571 in Healthy Japanese Participants(Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose)
- Fasted State Single Dose Cmax of Modified-Release (MR) Formulation of PF-06865571 in Healthy Participants(Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose)
- Fasted State Single Dose Tmax of MR Formulation of PF-06865571 in Healthy Participants(Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose)
- Fasted State Single Dose AUC(last) of MR Formulation of PF-06865571 in Healthy Participants(Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose)
- Single Dose AUC(0-∞) of MR Formulation of PF-06865571 in Healthy Participants(Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose)
- Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)(Baseline (Day -1) up to 35 days after last dose of study medication)
- Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities(Baseline (Day -1) and Day 3 of each period)