A Multiple 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 multiple 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 Administration Of Multiple Escalating Oral Doses In Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-06678552
* Drug: Placebo
* Drug: PF-06678552
* Drug: Placebo
* Drug: PF-06678552
* Drug: Placebo
* Drug: PF-06678552
* Drug: Placebo
* Drug: PF-06678552
* Drug: Placebo
* Drug: PF-06678552
* Drug: 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Single dose level of PF-06678552 or placebo every 12 hours (Q12H) for 14 days to investigate the safety, tolerability, and pharmacokinetics. | Drug: PF-06678552<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.<br>Drug: Placebo<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.<br>|
| Experimental: Cohort 2<br>Single dose level of PF-06678552 or placebo every 12 hours (Q12H) for 14 days to investigate the safety, tolerability, and pharmacokinetics. | Drug: PF-06678552<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.<br>Drug: Placebo<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.<br>|
| Experimental: Cohort 3<br>Single dose level of PF-06678552 or placebo every 12 hours (Q12H) for 14 days to investigate the safety, tolerability, and pharmacokinetics. | Drug: PF-06678552<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.<br>Drug: Placebo<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.<br>|
| Experimental: Cohort 4<br>Single dose level of PF-06678552 or placebo every 12 hours (Q12H) for 14 days to investigate the safety, tolerability, and pharmacokinetics. | Drug: PF-06678552<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.<br>Drug: Placebo<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.<br>|
| Experimental: Cohort 5<br>Single dose level of PF-06678552 or placebo will be provided either once daily (QD), every 12 hours (Q12H), or every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics. | Drug: PF-06678552<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution either once daily (QD), every 12 hours (Q12H), or every 8 hours (Q8H) for 14 days.<br>Drug: Placebo<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution either once daily (QD), every 12 hours (Q12H), or every 8 hours (Q8H) for 14 days.<br>|
| Experimental: Cohort 6<br>Single dose level of PF-06678552 or placebo will be provided either once daily (QD), every 12 hours (Q12H), or every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics. | Drug: PF-06678552<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution either once daily (QD), every 12 hours (Q12H), or every 8 hours (Q8H) for 14 days.<br>Drug: Placebo<br>* PF-06678552 or placebo will be administered as an extemporaneously prepared solution either once daily (QD), every 12 hours (Q12H), or every 8 hours (Q8H) for 14 days.<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 by 12 lead ECG. |  | 0 to 24 days 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-06644927 on day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06644927 on day 7 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06644927 on day 14 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Area Under the Curve during the dosing interval (AUCtau) for PF-06644927 on day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Area Under the Curve during the dosing interval (AUCtau) for PF-06644927 on day 7 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Area Under the Curve during the dosing interval (AUCtau) for PF-06644927 on day 14 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06644927 on day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06644927 on day 7 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06644927 on day 14 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06644927 on day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06644927 on day 7 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06644927 on day 14 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Plasma Decay Half-Life (t1/2) for PF-06644927 on day 14 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48 hours post dose | 
| Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06644927 on day 7 relative to day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06644927 on day 14 relative to day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUC)) for PF-06644927 on day 7 relative to day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUC)) for PF-06644927 on day 14 relative to day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Amount of PF-06644927 excreted in urine (Ae) on day 14 |  | 0-12 hours post dose | 
| Percent of dose excreted in urine as PF-06644927 (Ae%) on day 14 |  | 0-12 hours post dose | 
| Renal clearance of PF-06644927 (CLr) on day 14 |  | 0-12 hours post dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06678552 on day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06678552 on day 7 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06678552 on day 14 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Area Under the Curve during the dosing interval (AUCtau) for PF-06678552 on day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Area Under the Curve during the dosing interval (AUCtau) for PF-06678552 on day 7 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Area Under the Curve during the dosing interval (AUCtau) for PF-06678552 on day 14 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06678552 on day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06678552 on day 7 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06678552 on day 14 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06678552 on day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06678552 on day 7 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Plasma Decay Half-Life (t1/2) for PF-06678552 on day 14 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48 hours post dose | 
| Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06678552 on day 7 relative to day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06678552 on day 14 relative to day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUC)) for PF-06678552 on day 7 relative to day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUC)) for PF-06678552 on day 14 relative to day 1 |  | 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Apparent Oral Clearance (CL/F) of PF-06678552 on day 7 | 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, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Apparent Oral Clearance (CL/F) of PF-06678552 on day 14 | 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, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Apparent Volume of Distribution (Vz/F) of PF-06678552 on day 7 | 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, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 
| Apparent Volume of Distribution (Vz/F) of PF-06678552 on day 14 | 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, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose | 

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