A Single Oral Dose Study Of PF-06427878 In Healthy Adult Subjects

Study Overview
=================
Brief Summary
-----------------
PF-06427878 is a new compound proposed for the treatment of hyperlipidemia. The primary purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of single oral doses of PF-06427878 in healthy adult subjects.

Official Title
-----------------
A Phase 1, Randomized, Double-blind, Placebo-controlled Study To Assess The Safety, Tolerability, And Pharmacokinetics Of Single Escalating Oral Doses Of Pf-06427878 Co-administered With Meal In Healthy Adult Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: PF-06427878
* Drug: Placebo
* Drug: PF-06427878
* Drug: Placebo
* Drug: PF-06427878
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male and/or female subjects of non childbearing potential. Body Mass Index (BMI) of 17.5 to 35.4 kg/m2; and a total body weight >50 kg Subjects with fasting TG level of >=90 mg/dL and <=500 mg/dL following an overnight fast Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1-PF-06427878 or placebo<br>Single ascending doses of PF-06427878 or placebo to investigate the safety, tolerability, and PK. | Drug: PF-06427878<br>* PF-06427878 or placebo will be administered once in each period as an extemporaneously prepared suspension.<br>Drug: Placebo<br>* PF-06427878 or placebo will be administered once in each period as an extemporaneously prepared suspension.<br>|
| Experimental: Cohort 2-PF-06427878 or placebo<br>Single ascending doses of PF-06427878 or placebo to investigate the safety, tolerability, and PK. | Drug: PF-06427878<br>* PF-06427878 or placebo will be administered once in each period as an extemporaneously prepared suspension.<br>Drug: Placebo<br>* PF-06427878 or placebo will be administered once in each period as an extemporaneously prepared suspension.<br>|
| Experimental: Cohort 3-PF-06427878 or placebo<br>Single ascending doses of PF-06427878 or placebo to investigate the safety, tolerability, and PK. | Drug: PF-06427878<br>* PF-06427878 or placebo will be administered once in each period as an extemporaneously prepared suspension.<br>Drug: Placebo<br>* PF-06427878 or placebo will be administered once in each period as an extemporaneously prepared suspension.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of adverse events (AEs). |  | 0-48 h post dose | 
| Assessment of clinical laboratory tests. |  | 0-48 h post dose | 
| Assessment of vital signs (including blood pressure and pulse rate). |  | 0-48 h post dose | 
| Assessment of cardiac conduction intervals as assessed via 12-lead electrocardiogram (ECG). |  | 0-48 h post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06427878 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf)] for PF-06427878 | AUC (0 - inf)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06427878 |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post dose | 
| Apparent Oral Clearance (CL/F) for PF-06427878 | 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. Clearance was estimated from population pharmacokinetic (PK) modeling. 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, 8, 10, 12, 24, 48 hours post dose | 
| Apparent Volume of Distribution (Vz/F) for PF-06427878 | 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, 8, 10, 12, 24, 48 hours post dose | 
| Plasma Decay Half-Life (t1/2) for PF-06427878 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Single Ascending Dose, healthy subjects, Hyperlipidemia, Lipid Metabolism Disorders, Metabolic Diseases