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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia	Biological: PF-05335810 Dose A; Biological: PF-05335810 Dose B; Biological: Placebo; Biological: PF-04950615 Dose A; Biological: PF-05335810 Dose C; Biological: PF-04950615; Biological: PF-05335810 Dose D; Biological: PF-05335810 Dose E	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	136 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Basic Science
Official Title:	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
Study Start Date :	July 2012
Actual Primary Completion Date :	October 2013
Actual Study Completion Date :	October 2013

Arms and Interventions

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

Outcome Measures

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Primary Outcome Measures :

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Day 85/169 or Early Termination (ET) ]
   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.
2. Number of Participants With Laboratory Test Values of Potential Clinical Importance [ Time Frame: Baseline up to Day 85/169 or Early Termination (ET) ]
   Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance.
3. Change From Baseline in Heart Rate [ Time Frame: Baseline, Day 1 to 85/169 or ET ]
4. Diastolic Blood Pressure [ Time Frame: Baseline, Day 1 to 85/169 or ET ]
5. Change From Baseline in Electrocardiogram (ECG) Parameters [ Time Frame: Baseline, Day 1 to 85/169 or ET ]
6. Number of Participants With Laboratory Test Values of Potential Clinical Importance [ Time Frame: Baseline, Day 1 to 85/169 or ET ]
   Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance.

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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%).

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Connecticut
Pfizer Investigational Site
New Haven, Connecticut, United States, 06511
United States, Florida
Pfizer Investigational Site
Miami, Florida, United States, 33169
Pfizer Investigational Site
South Miami, Florida, United States, 33143
United States, Kansas
Pfizer Investigational Site
Overland Park, Kansas, United States, 66212
United States, Michigan
Pfizer Investigational Site
Kalamazoo, Michigan, United States, 49007
United States, Ohio
Pfizer Investigational Site
Cincinnati, Ohio, United States, 45227
United States, Texas
Pfizer Investigational Site
San Antonio, Texas, United States, 78209

Sponsors and Collaborators

Pfizer

Investigators

Study Director:	Pfizer CT.gov Call Center	Pfizer

More Information

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Additional Information:

To obtain contact information for a study center near you, click here. 

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT01720537 History of Changes
Other Study ID Numbers:	B3091001
First Posted:	November 2, 2012
Last Update Posted:	November 20, 2013
Last Verified:	November 2013

Keywords provided by Pfizer:

High Cholesterol; Dyslipidemia

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases