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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Be-bru
    • Brussels, Be-bru, Belgium, B-1070
      • Brussels Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2019
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): October 31, 2019

Study Registration Dates

• First Submitted: August 1, 2019
• First Submitted That Met QC Criteria: August 1, 2019
• First Posted (Actual): August 2, 2019

Study Record Updates

• Last Update Posted (Actual): November 27, 2019
• Last Update Submitted That Met QC Criteria: November 25, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Japanese; Relative bioavailability; Modified release; PF-06865571; Diacylglycerol acyltransferase; DGAT2
• Other Study ID Numbers: C2541012; 2019-001426-96 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes