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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01720537
First received: August 3, 2012
Last updated: November 19, 2013
Last verified: November 2013
  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
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, 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:


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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
  • Diastolic Blood Pressure [ Time Frame: Baseline, Day 1 to 85/169 or ET ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Electrocardiogram (ECG) Parameters [ Time Frame: Baseline, Day 1 to 85/169 or ET ] [ Designated as safety issue: Yes ]
  • Number of Participants With Laboratory Test Values of Potential Clinical Importance [ Time Frame: Baseline, Day 1 to 85/169 or ET ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Day1 pre-dose to Day 85/169 or ET ] [ Designated as safety issue: No ]
  • Apparent Volume of Distribution (Vz/F) [ Time Frame: Day1 pre-dose to Day 85/169 or ET ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

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
Genders Eligible for Study:   Both
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:
No publications provided

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
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
High Cholesterol
Dyslipidemia

Additional relevant MeSH terms:
Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 22, 2014