A Multiple Dose Study of PF-04950615 (RN316) in Subjects on High 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 High Doses Of Atorvastatin, Rosuvastatin Or Simvastatin.

This study will investigate the effect of PF-04950615, a new investigational lipid lowering agent, on LDL-C and other lipids.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 93
• 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
  • California
    • Tustin, California, United States, 92780
      • Orange County Research Center
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Doral, Florida, United States, 33166
      • In Vivo Clinical Research, Inc.
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Miami, Florida, United States, 33185
      • Kendall South Medical Center
  • Georgia
    • Woodstock, Georgia, United States, 30189
      • North Georgia Clinical Research
    • Woodstock, Georgia, United States, 30189
      • North Georgia Internal Medicine
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
    • Madisonville, Kentucky, United States, 42431
      • Commonwealth Biomedical Research, LLC
  • Maine
    • Auburn, Maine, United States, 04210
      • Maine Research Associates
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Infinity Medical Research
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research, P.C.
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Lipid and Diabetes Research Center
    • Saint Louis, Missouri, United States, 63117
      • Medex Healthcare Research, Inc.
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • New Mexico Clinical Research & Osteoporosis Center, Incorporated
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • North Carolina Clinical Research
    • Salisbury, North Carolina, United States, 28144
      • PMG Research of Salisbury
  • 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 Heart Hospital Physicians
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Cardiovascular Research Group (OCRG)
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman Center for Advanced Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • Translational Research Center
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center for Clinical Research
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group
  • Texas
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
    • San Antonio, Texas, United States, 78205
      • Paragon Research Center, LLC
    • San Antonio, Texas, United States, 78229
      • San Antonio Preventive & Diagnostic Medicine, PA
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • National Clinical Research - Norfolk, Inc.
    • 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:

• On a stable daily dose of atorvastatin, rosuvastatin or simvastatin.
• Lipids meet the following criteria at screening and prior to dosing: Fasting LDL-C greater than 100 mg/dL and fasting TG less than 400 mg/dL

Exclusion Criteria:

• History of a cardiovascular or cerebrovascular event or procedure during the past year.
• Poorly controlled type 1 or type 2 diabetes mellitus.
• Poorly controlled hypertension.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment B	Drug: Statin; Single daily dose of atorvastatin (40 or 80 mg), rosuvastatin (20 or 40 mg) or simvastatin (40 or 80 mg) from Day 1 to Day 141/ET.; Biological: PF-04950615 (RN316); Intravenous 10mg/mL based on weight monthly during treatment phase.
Experimental: Treatment C	Drug: Statin; Single daily dose of atorvastatin (40 or 80 mg), rosuvastatin (20 or 40 mg) or simvastatin (40 or 80 mg) from Day 1 to Day 141/ET.; Biological: PF-04950615 (RN316); Intravenous 10mg/mL based on weight monthly during treatment phase.
Experimental: Treatment D	Biological: PF-04950615 (RN316); Intravenous 10mg/mL based on weight monthly during treatment phase.; Drug: Satin; Single daily dose of atorvastatin (40 or 80 mg), rosuvastatin (20 or 40 mg) or simvastatin (40 or 80 mg) from Day 1 to Day 141/ET.
Placebo Comparator: Treatment A	Biological: Placebo; Intravenous placebo monthly during treatment phase.; Drug: Statin; Single daily dose of atorvastatin (40 or 80 mg), rosuvastatin (20 or 40 mg) or simvastatin (40 or 80 mg) from Day 1 to Day 141/ET.
Experimental: Treatment E	Drug: Statin; Single daily dose of atorvastatin (40 or 80 mg), rosuvastatin (20 or 40 mg) or simvastatin (40 or 80 mg) from Day 1 to Day 141/ET.; Biological: PF-04950615 (RN316); Intravenous 10mg/mL based on weight monthly during treatment phase.

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 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
Percentage of Participants Achieving Low-density Lipoprotein Cholesterol (LDL-C) Less Than (<) 70 and <100 Milligram Per Deciliter (mg/dL)		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, SAEs 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 attributed to study drug in a participant who received study drug. Investigator assessed TEAEs as mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) or severe (interfered significantly with participant's usual function). 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 Relevant Laboratory Abnormalities	Hematology (hemoglobin[hgb],hematocrit,red blood cell[RBC]<0.8*lower limit of normal[LLN],mean cell[MC] volume,MC hgb,MC hg concentration <0.9*LLN, greater than[>] 1.1*upper limit of normal[ULN], platelet <0.5*LLN,>1.75*ULN, white blood cell[WBC]<0.6*LLN,>1.5*ULN,neutrophil,lymphocyte <0.8*LLN,>1.2*ULN,eosinophil,basophil,monocyte >1.2*ULN);chemistry(total, direct, indirect bilirubin[BR]>1.5*ULN,aspartate aminotransferase[AT],alanine AT,alkaline phosphatase,gamma-glutyl transferase>3.0*ULN,protein,lactate dehydrogenase <0.8*LLN,>1.2*ULN,creatinine,blood urea nitrogen>1.3*ULN,uric acid >1.2*ULN,potassium,chloride,calcium,bicarbonate<0.9*LLN,>1.1*ULN, sodium<0.95*LLN,>1.05*ULN,glucose[GL]<0.6*LLN,>1.5*ULN,amylase,lipase >1.5*ULN,creatinine kinase>2.0*ULN);urinalysis(pH <4.5,>8,specific gravity<1.003 , >1.030, GL,ketone,protein,hgb,BR,nitrite,leukocyte greater than or equal to [>=]1, RBC, WBC >=20);coagulation(prothrombin[PT],PT international ratio,partial thromboplastin time>1.1*ULN).	Day 1 up to Day 141
Number of Participants With Clinically Significant Changes in Vital Signs and Electrocardiogram (ECG) Parameters	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 >200 millisecond (msec) and 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 >30 to <=60 msec and maximum increase from baseline of >60 msec for QT interval corrected using the Fridericia's formula (QTCF).	Day 1 up to Day 141
Number of Participants With Anti-drug Antibody (ADA)	Human serum ADA samples of participants who received PF-04950615 (RN316) were analyzed for the presence of anti-PF-04950615 (RN316) 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Lipoprotein (a) (Lp[a]) at Day 29, 57, 71, 85, 99, 127 and 141	Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration.	Baseline, Day 29, 57, 71, 85, 99, 127, 141
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Day 29, 57, 71, 85, 99, 127 and 141	Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration.	Baseline, Day 29, 57, 71, 85, 99, 127, 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): July 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: April 25, 2011
• First Submitted That Met QC Criteria: April 25, 2011
• First Posted (Estimate): April 27, 2011

Study Record Updates

• Last Update Posted (Actual): October 11, 2017
• Last Update Submitted That Met QC Criteria: September 11, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: PF-04950615; RN316
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Bococizumab
• Other Study ID Numbers: B1481005