A Study To Assess The Safety Of PF-05335810 In Hypercholesterolemic Subjects

Study Overview
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Brief Summary
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This study is to evaluate the safety, tolerability and immunogenicity of single, ascending or multiple fixed subcutaneous and intravenous administrations of PF 05335810 to hypercholesterolemic subjects when added on to a daily statin dose.

Official Title
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A Phase I, Placebo-Controlled, Randomized Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Following Single, Ascending Doses Of PF-05335810 In Hypercholesterolemic Subjects, With One, Open-Label, Multiple Fixed Dosage Cohort

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Biological: PF-05335810 Dose A
* Biological: PF-05335810 Dose B
* Biological: Placebo
* Biological: PF-05335810 Dose B
* Biological: Placebo
* Biological: PF-04950615 Dose A
* Biological: PF-04950615 Dose A
* Biological: PF-05335810 Dose C
* Biological: Placebo
* Biological: PF-05335810 Dose C
* Biological: Placebo
* Biological: PF-04950615
* Biological: PF-05335810 Dose D
* Biological: Placebo
* Biological: PF-05335810 Dose E
* Biological: PF-05335810 Dose D
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: On stable daily doses of a statin for 45 days prior to receiving study treatment. Fasting LDL C equal or greater than 80 mg/dL at screening and visit approximately 1 week prior to randomization. Exclusion Criteria: History of a cardiovascular or cerebrovascular event or procedure within one year of randomization. Poorly controlled type 1 or type 2 diabetes mellitus (defined as HbA1c >9%).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br> | Biological: PF-05335810 Dose A<br>* Single SC Injection<br>|
| Experimental: Cohort 2<br> | Biological: PF-05335810 Dose B<br>* Single Subcutaneous Injection(s)<br>Biological: Placebo<br>* Single Subcutaneous Injection(s)<br>Biological: PF-05335810 Dose B<br>* Single Intravenous Infusion<br>Biological: Placebo<br>* Single Intravenous Infusion<br>Biological: PF-04950615 Dose A<br>* Single Subcutaneous Injection(s)<br>Biological: PF-04950615 Dose A<br>* Single Intravenous Infusion<br>|
| Experimental: Cohort 3<br> | Biological: PF-05335810 Dose C<br>* Single Subcutaneous Injection(s)<br>Biological: Placebo<br>* Single Subcutaneous Injection(s)<br>Biological: PF-05335810 Dose C<br>* Single Intravenous Infusion<br>Biological: Placebo<br>* Single Intravenous Infusion<br>Biological: PF-04950615<br>* Single Subcutaneous Injection(s)<br>|
| Experimental: Cohort 4<br> | Biological: PF-05335810 Dose D<br>* Single Subcutaneous Injection(s)<br>Biological: Placebo<br>* Single Subcutaneous Injection(s)<br>|
| Experimental: Cohort 5<br> | Biological: PF-05335810 Dose E<br>* Multiple fixed dosages administered in subcutaneous injections, monthly for 3 months.<br>|
| Experimental: Cohort 6<br> | Biological: PF-05335810 Dose D<br>* Single Intravenous Infusion<br>Biological: Placebo<br>* Single Intravenous Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to [study drug] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. | Baseline up to Day 85/169 or Early Termination (ET) | 
| Number of Participants With Laboratory Test Values of Potential Clinical Importance | Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance. | Baseline up to Day 85/169 or Early Termination (ET) | 
| Change From Baseline in Heart Rate |  | Baseline, Day 1 to 85/169 or ET | 
| Diastolic Blood Pressure |  | Baseline, Day 1 to 85/169 or ET | 
| Change From Baseline in Electrocardiogram (ECG) Parameters |  | Baseline, Day 1 to 85/169 or ET | 
| Number of Participants With Laboratory Test Values of Potential Clinical Importance | Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance. | Baseline, Day 1 to 85/169 or ET | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] | AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). | Day1 pre-dose to Day 85/169 or ET | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) | Day1 pre-dose to Day 85/169 or ET | 
| Maximum Observed Plasma Concentration (Cmax) |  | Day1 pre-dose to Day 85/169 or ET | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | Day1 pre-dose to Day 85/169 or ET | 
| Apparent Volume of Distribution (Vz/F) | 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. | Day1 pre-dose to Day 85/169 or ET | 
| Apparent Oral Clearance (CL/F) | 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. | Day1 pre-dose to Day 85/169 or ET | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day1 pre-dose to Day 85/169 or ET | 
| Absolute Bioavailability (%F) |  | Day1 pre-dose to Day 85/169 or ET | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High Cholesterol, Dyslipidemia