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

Purpose

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	Intervention	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 Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: Cholesterol

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

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.
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.
Change From Baseline in Heart Rate [ Time Frame: Baseline, Day 1 to 85/169 or ET ]
Diastolic Blood Pressure [ Time Frame: Baseline, Day 1 to 85/169 or ET ]
Change From Baseline in Electrocardiogram (ECG) Parameters [ Time Frame: Baseline, Day 1 to 85/169 or ET ]
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:

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).
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)
Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day1 pre-dose to Day 85/169 or ET ]
Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Day1 pre-dose to Day 85/169 or ET ]
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.
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.
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.
Absolute Bioavailability (%F) [ Time Frame: Day1 pre-dose to Day 85/169 or ET ]


Enrollment:	136
Study Start Date:	July 2012
Study Completion Date:	October 2013
Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility


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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01720537

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

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site


Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT01720537 History of Changes
Other Study ID Numbers:	B3091001
Study First Received:	August 3, 2012
Last Updated:	November 19, 2013

Keywords provided by Pfizer:


High Cholesterol Dyslipidemia

Additional relevant MeSH terms:


Hypercholesterolemia Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases

ClinicalTrials.gov processed this record on August 21, 2017