A Single Dose Study Of PF-06678552 In Healthy Subjects

Study Overview
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Brief Summary
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PF-06678552 is a new compound proposed for the treatment of hypercholesteremia. The primary purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of PF-06678552 in healthy subjects.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study To Assess The Safety, Tolerability, And Pharmacokinetics Of PF-06678552 After Fed And Fasted Administration Of Single Escalating Oral Doses In Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-06678552 or Placebo
* Drug: PF-06678552 or Placebo
* Drug: PF-06678552 or Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects of non childbearing potential. Body Mass Index (BMI) of 18 to 30.5 kg/m2; and a total body weight >50 kg Low density lipoprotein cholesterol between 115 mg/dL and 190 mg/dL 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
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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: Cohort 1<br>Single ascending doses of PF-06678552 or placebo to investigate the safety, tolerability, PK, and PD. | Drug: PF-06678552 or Placebo<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution once in each period.<br>|
| Experimental: Cohort 2<br>Single ascending doses of PF-06678552 or placebo to investigate the safety, tolerability, PK, and PD. | Drug: PF-06678552 or Placebo<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution once in each period.<br>|
| Experimental: Cohort 3<br>Single ascending doses of PF-06678552 or placebo to investigate the safety, tolerability, PK, and PD. | Drug: PF-06678552 or Placebo<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution once in each period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of adverse events (AEs), clinical laboratory tests, vital signs (including blood pressure and pulse rate) and cardiac conduction intervals as assessed via 12-lead electrocardiogram (ECG). |  | 0 to 72 hours 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-06678552 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - infinity)] for PF-06678552 | 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, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for for PF-06678552 | Maximum Observed Plasma Concentration (Cmax) | 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06678552 | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 
| Plasma Decay Half-Life (t1/2) for PF-06678552 | Plasma Decay Half-Life (t1/2) | 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 
| Apparent Oral Clearance (CL/F) for PF-06678552 | 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, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 
| Apparent Volume of Distribution (Vz/F) for PF-06678552 | 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, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06644927 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - infinity)] for PF-06644927 | 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, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06644927 | Maximum Observed Plasma Concentration (Cmax) | 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06644927 | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 
| Plasma Decay Half-Life (t1/2) for PF-06644927 | Plasma Decay Half-Life (t1/2) | 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose | 
| Amount of PF-06644927 excreted in the urine (Ae) | Amount of drug excreted in the urine is a measure of the degree that the kidneys filter drug from the blood to the urine. | 0-4, 4-12, and 12-24 hours post dose | 
| Percent of PF-06678552 dose excreted in the urine as PF-06644927 (Ae%) | The percent of PF-06678552 dose excreted in the urine as PF-06644927 is calculated from the mass of dose excreted in the urine compared to the total dose of PF-06678552 and corrected for the relative weight of PF-06644927 to PF-06678552. | 0-4, 4-12, and 12-24 hours post dose | 
| Renal Clearance (CLr) for PF-06644927 | Renal clearance is the measure of the rate of drug moving into the urine from blood | 0-4, 4-12, and 12-24 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single Ascending Dose, healthy subjects, Hypercholesterolemia, Hyperlipidemias, Dyslipidemias, Lipid Metabolism Disorders, Metabolic Diseases