A Multiple Dose Study Of PF-04950615 (RN316) In Subjects On Maximum Doses Of Statins

A Phase 2, Double-blind, Placebo-controlled, Randomized Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 Following Multiple Intravenous Doses In Hypercholesterolemic Subjects On Maximum Dose Of Atorvastatin Or Rosuvastatin.

PF-04950615 is a new investigational hypercholesterolemic agent that is being tested in this study to evaluate if it can lower LDL cholesterol.

Study Overview

• Status: Completed
• Conditions: Dyslipidemia; Hypercholesterolemia
• Intervention / Treatment: Other: Placebo; Drug: PF-04950615 (RN316)

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4M6
    • Clinique des Maladies Lipidiques de Quebec Inc.
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 3G8
      • The Medical Arts Health Research Group
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7Y8
      • Q & T Research Chicoutimi
    • Laval, Quebec, Canada, H7T 2P5
      • Centre de Recherche Clinique de Laval
    • Montreal, Quebec, Canada, H4N 3C5
      • Diex Research Montreal Inc.
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • Diex Research Sherbrooke Inc.
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
  • California
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, Inc
    • Garden Grove, California, United States, 92845
      • Advance Outcome Management, Inc.
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network, Inc.
    • Wildomar, California, United States, 92595
      • Elite Clinical Trials, Inc.
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Miami, Florida, United States, 33185
      • Kendall South Medical Center, Inc.
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta Diabetes Associates
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research
    • Overland Park, Kansas, United States, 66209
      • Midwest Cardiology Associates
    • Overland Park, Kansas, United States, 66209
      • Stark Pharmacy
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Lipid and Diabetes Research Center
    • Saint Louis, Missouri, United States, 63128
      • Advance Clinical Research
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Internal Medicine Consultants, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Heart Hospital
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Cardiovascular Research Group
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Heart Hospital Physicians
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • DeGarmo Institute of Medical Research
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
  • Texas
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc
    • Tomball, Texas, United States, 77375
      • Martin Diagnostic Clinic
  • Utah
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research, LLC
  • Virginia
    • Richmond, Virginia, United States, 23294
      • National Clinical Research - Richmond, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body Mass Index (BMI) of 18.5 to 40 kg/m2
• On a stable maximum daily dose of a statin, defined as atorvastatin 80 mg or rosuvastatin 40 mg for a minimum of 45 days prior to Day 1.
• Lipids meet the following criteria twice during screening period:
• Fasting LDL C = or > 80 mg/dL;
• Fasting TG < 400 mg/dL.

Exclusion Criteria:

• History of a cardiovascular or cerebrovascular event or procedure (eg, MI, stroke, TIA, angioplasty) during the past year.
• Poorly controlled type 1 or type 2 diabetes mellitus.
• Poorly controlled hypertension.
• Fasting triglycerides > 400 mg/dL
• 12 lead ECG demonstrating QTcFF >455 msec at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment B	Drug: PF-04950615 (RN316); An infusion lasting approximately 60 minutes
Experimental: Treatment C	Drug: PF-04950615 (RN316); An infusion lasting approximately 60 minutes
Placebo Comparator: Treatment A	Other: Placebo; An infusion lasting approximately 60 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Day 85	Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration.	Baseline, Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Low-density Lipoprotein Cholesterol (LDL-C) Less Than 70 and Less Than 100 Milligram Per Deciliter (mg/dL)		Day 29, 57, 85
Percentage of Participants Achieving at Least 30 Percent Decrease in Low-density Lipoprotein Cholesterol (LDL-C)		Day 29, 57, 85
Change From Baseline in Lipid Parameters at Day 29, 57 and 85	Lipid parameters included: high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), non-high-density lipoprotein-cholesterol (non-HDL-C), triglyceride (TG), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1). Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration.	Baseline, Day 29, 57, 85
Percent Change From Baseline in Lipid Parameters at Day 29, 57 and 85	Lipid parameters included: high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), non-high-density lipoprotein-cholesterol (non-HDL-C), triglyceride (TG), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1). Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration.	Baseline, Day 29, 57, 85
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are events between first dose of study drug and up to Day 141 that were absent before treatment or that worsened relative to pretreatment state. Treatment related: a TEAE deemed related to the study drug by the investigator. TEAEs included SAEs (TESAEs) as well as non-serious AEs which occurred during the study. The participants with TEAEs, TESAEs and treatment-related TEAEs were reported.	Day 1 up to Day 141
Number of Treatment-Emergent Adverse Events (TEAEs) by Severity	An AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Investigator assessed adverse events as mild (does not interfere with participant's usual function), moderate (interferes to some extent with participant's usual function) or severe (interferes significantly with participant's usual function). All causality TEAEs were assessed for severity. TEAEs are events between first dose of study drug and up to Day 141 that were absent before treatment or that worsened relative to pretreatment state.	Day 1 up to Day 141
Number of Participants With Clinically Significant Laboratory Abnormalities	Criteria for clinically significant laboratory abnormalities were based on investigator's discretion. Total number of participants who met the criteria for any laboratory abnormal findings were reported. Laboratory parameters included: hematology, coagulation, liver function, renal function, electrolytes, hormones, chemistry and urinalysis. Screening was 21 days prior to start of study treatment.	Screening up to Day 141
Number of Participants With Clinically Significant Changes in Vital Signs and Electrocardiogram (ECG) Parameters	Number of participants with clinically significant changes in vital signs and ECG findings were reported. Criteria for clinical significant vital signs: maximum increase or decrease from baseline in supine systolic blood pressure (BP) greater than or equal to (>=) 30 millimeter of mercury (mmHg), maximum increase or decrease from baseline in supine diastolic BP of >=20 mmHg. Criteria for clinically significant ECG parameters: maximum increase of >=25 percent (%) for baseline value of greater than 200 millisecond (msec) or maximum increase of >=50% for baseline value of less than or equal to (<=) 200 msec for PR and QRS interval, maximum increase from baseline of greater than (>) 30 to <=60 msec and maximum increase from baseline of >60 msec for QT interval corrected using the Fridericia's formula (QTCF). Screening was 21 days prior to start of study treatment.	Screening up to Day 141
Number of Participants With Anti-drug (Anti-PF-04950615) Antibody (ADA)	Human serum samples of participants who received PF-04950615 (RN316) were analyzed for the presence of anti-PF-04950615 antibodies by using the semi quantitative enzyme-linked immunosorbent assay (ELISA). Results with titer value >=4.32 nanogram per milliliter of anti-PF-04950615 antibodies were counted as positive. Number of participants with presence of anti-PF-04950615 antibodies were reported in this outcome measure.	Day 1 up to Day 141

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Udata C, Garzone PD, Gumbiner B, Joh T, Liang H, Liao KH, Williams JH, Meng X. A Mechanism-Based Pharmacokinetic/Pharmacodynamic Model for Bococizumab, a Humanized Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, and Its Application in Early Clinical Development. J Clin Pharmacol. 2017 Jul;57(7):855-864. doi: 10.1002/jcph.867. Epub 2017 Feb 9.
• Wan H, Gumbiner B, Joh T, Riel T, Udata C, Forgues P, Garzone PD. Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition with Bococizumab on Lipoprotein Particles in Hypercholesterolemic Subjects. Clin Ther. 2017 Nov;39(11):2243-2259.e5. doi: 10.1016/j.clinthera.2017.09.009. Epub 2017 Oct 14.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2011
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: May 3, 2011
• First Submitted That Met QC Criteria: May 6, 2011
• First Posted (Estimate): May 9, 2011

Study Record Updates

• Last Update Posted (Actual): November 8, 2017
• Last Update Submitted That Met QC Criteria: October 4, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: antibody; Hypercholesterolemia; PCSK9; dyslipidemia; high cholesterol; LDL; PF-04950615; RN316
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Bococizumab
• Other Study ID Numbers: B1481012