Single Dose Study of PF-06815345 in Healthy Subjects

Study Overview
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Brief Summary
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The current study is the first clinical trial proposed with PF-06815345. It is designed to evaluate the safety, tolerability, and pharmacokinetics (PK) following administration of single oral doses of PF-06815345 to healthy adult subjects.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled Study To Assess Safety, Tolerability, And Pharmacokinetics Of Single Escalating Oral Doses Of Pf-06815345, As Well As Characterize The Pharmacokinetics Of Two Formulations And Effect Of Food On Pharmacokinetics Of One Formulation Of Pf-06815345 Administered To Healthy Adult Subjects

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: PF-06815345
* Other: Placebo
* Drug: PF-06815345


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and female of non-childbearing potential; Age of 18-55, inclusive; Body Mass Index 17.5-34.9 kg/m2, inclusive; Body weight >50 kg; Not on any prescription or non-prescription drugs within 7 days or 5 half-lives prior to first dose. Exclusion Criteria: - Evidence of history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergises, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1_Cohort 1_Active;<br>Single ascending dose of PF-06815345 | Drug: PF-06815345<br>* PF-06815345 will be administered as a liquid dosage formulation<br>|
| Placebo Comparator: Part 1_Cohort 1_Placebo;<br>Single dose of placebo | Other: Placebo<br>* Placebo<br>|
| Experimental: Part 1_Cohort 2_Active<br>Single ascending dose of PF-06815345 | Drug: PF-06815345<br>* PF-06815345 will be administered as a liquid dosage formulation<br>|
| Placebo Comparator: Part 1_Cohort 2_Placebo<br>Single dose of placebo | Other: Placebo<br>* Placebo<br>|
| Experimental: Part 2<br>Single dose of solid dosage formulation (test) versus liquid dosage formulation (reference) of PF-06815345 | Drug: PF-06815345<br>* PF-06815345 will be administered as either solid dosage formulation or liquid dosage formulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Treatment Emergent Treatment-Related Adverse Events (AEs) | Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject 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 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to Drug was assessed by the investigator (Yes/No). Subjects with multiple occurrences of an AE within a category were counted once within the category. | Baseline (Day 0) up to 28 days after last dose of study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06815345 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | 0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0- infinity)] for PF-06815345 | AUC (0-infinity)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-infinity). It is obtained from AUC (0-t) plus AUC (t-infinity). | 0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06815345 | Maximum Observed Plasma Concentration (Cmax) | 0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose | 
| Time to Reach Maximum Observed Concentration for PF-06815345 | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose | 
| Plasma Decay Half-Life (t1/2) for PF-06815345 | Plasma Decay Half-Life (t1/2) | 0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose | 
| Apparent Oral Clearance (CL/F) for PF-06815345 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | 0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose | 
| Apparent Volume of Distribution (Vz/F) for PF-06815345 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | 0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for the metabolite (PF-06811701) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | 0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0- infinity)] for metabolite (PF-06811701) | AUC (0-infinity)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-infinity). It is obtained from AUC (0-t) plus AUC (t-infinity). | 0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for metabolite (PF-06811701) | Maximum Observed Plasma Concentration (Cmax) | 0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose | 
| Time to Reach Maximum Observed Concentration for metabolite (PF-06811701) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose | 
| Plasma Decay Half-Life (t1/2) for metabolite (PF-06811701) | Plasma Decay Half-Life (t1/2) | 0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy subjects, Single Ascending Dose, Hyperlipidemia, Dyslipidemia