Relative Bioavailability Study of a Modified-Release Formulation of PF-06865571 in Healthy Adult Participants

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: PF-06865571 400 mg Immediate Release (IR) in Fed State
* Drug: PF-06865571 50 mg Modified Release (MR) in Fed State
* Drug: PF-06865571 400 mg MR in Fed State
* Drug: PF-06865571 400 mg MR in Fasted State


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Relative Bioavailability<br>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 | Drug: PF-06865571 400 mg Immediate Release (IR) in Fed State<br>* 400 mg IR dose in fed state<br>Drug: PF-06865571 50 mg Modified Release (MR) in Fed State<br>* 50 mg MR in fed state<br>Drug: PF-06865571 400 mg MR in Fed State<br>* 400 mg MR in fed state<br>Drug: PF-06865571 400 mg MR in Fasted State<br>* 400 mg MR in fasted state<br>|
| Experimental: Fasted State<br>Comparison of 400 mg MR in fed and fasted states | Drug: PF-06865571 400 mg MR in Fed State<br>* 400 mg MR in fed state<br>Drug: PF-06865571 400 mg MR in Fasted State<br>* 400 mg MR in fasted state<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Dose Maximum Observed Plasma Concentration (Cmax) of PF-06865571 in Healthy Participants | All study participants | Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose | 
| Single Dose Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06865571 in Healthy Participants | All study participants | Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose | 
| Single Dose Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC(last)] of PF-06865571 in Healthy Participants | All study participants | Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose | 
| Single Dose Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC(0-∞)] of PF-06865571 in Healthy Participants | All study participants | Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Dose Cmax of PF-06865571 in Healthy Japanese Participants | Japanese participants only | 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 | Japanese participants only | 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 | Japanese participants only | 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 | Japanese participants only | 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 | All study 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 | All study 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 | All study 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 | All study 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) | Treatment-related AEs are any untoward medical occurrences attributed to study drug in a participant who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Y days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to Drug X was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. | 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 | Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test [for all female participants]) and urine (urine pregnancy test [for all female participants]). Clinical significance of laboratory parameters was determined at the investigator's discretion. | Baseline (Day -1) and Day 3 of each period | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Vital signs (temperature, respiratory rate, pulse, systolic and diastolic blood pressure) were obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Clinical significance of vital signs was determined at the investigator's discretion. | 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 | Criteria for potentially clinically important (PCI) changes in ECG (12-lead) were defined as: no sinus rhythm; PR interval >=220 msec and increase of >=20 msec; QRS interval >=120 msec; QT interval corrected using the Fridericia formula (QTcF) and QT interval corrected using the Bazett's formula (QTcB) >500 msec or increase of >60 msec; heart rate <=45 beats per minute (bpm) or >=120 bpm or decrease/increase of >=15 bpm. | Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PF-06865571, Relative bioavailability, Modified release, Diacylglycerol acyltransferase, DGAT2, Japanese