Clinical trial NCT04044053: Relative Bioavailability Study of a Modified-Release Formulation of PF-06865571 in Healthy Adult Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: PF-06865571
Relative bioavailability
Modified release
Diacylglycerol acyltransferase
DGAT2
Japanese
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2019-08-02
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


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.

Primary outcomes:
measure: Single Dose Maximum Observed Plasma Concentration (Cmax) of PF-06865571 in Healthy Participants
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
measure: Single Dose Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06865571 in Healthy Participants
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
measure: Single Dose Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC(last)] of PF-06865571 in Healthy Participants
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
measure: Single Dose Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC(0-∞)] of PF-06865571 in Healthy Participants
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
Secondary outcomes:
measure: Single Dose Cmax of PF-06865571 in Healthy Japanese Participants
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
measure: Single Dose Tmax of PF-06865571 in Healthy Japanese Participants
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
measure: Single Dose AUC(last) of PF-06865571 in Healthy Japanese Participants
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
measure: Single Dose AUC(0-∞) of PF-06865571 in Healthy Japanese Participants
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
measure: Fasted State Single Dose Cmax of Modified-Release (MR) Formulation of PF-06865571 in Healthy Participants
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
measure: Fasted State Single Dose Tmax of MR Formulation of PF-06865571 in Healthy Participants
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
measure: Fasted State Single Dose AUC(last) of MR Formulation of PF-06865571 in Healthy Participants
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
measure: Single Dose AUC(0-∞) of MR Formulation of PF-06865571 in Healthy Participants
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
measure: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
timeFrame: Baseline (Day -1) up to 35 days after last dose of study medication
measure: Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities
timeFrame: Baseline (Day -1) and Day 3 of each period
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
measure: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Brussels Clinical Research Unit
state: Be-bru
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: