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A Multiple Dose Study of PF-04950615 (RN316) in Subjects on High Doses of Statins

Phase 2
Completed
Conditions
Hypercholesterolemia
Dyslipidemia
Interventions
Biological: Placebo
Biological: PF-04950615 (RN316)
Drug: Satin
Registration Number
NCT01342211
Lead Sponsor
Pfizer
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
93
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Treatment EStatin-
Treatment APlacebo-
Treatment AStatin-
Treatment BPF-04950615 (RN316)-
Treatment BStatin-
Treatment CPF-04950615 (RN316)-
Treatment CStatin-
Treatment DPF-04950615 (RN316)-
Treatment DSatin-
Treatment EPF-04950615 (RN316)-
Primary Outcome Measures
NameTimeMethod
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Day 85Baseline, Day 85

Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)Day 1 up to Day 141

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.

Number of Participants With Clinically Relevant Laboratory AbnormalitiesDay 1 up to Day 141

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).

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 Anti-drug Antibody (ADA)Day 1 up to Day 141

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.

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 85Baseline, Day 29, 57, 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.

Percent Change From Baseline in Lipid Parameters at Day 29, 57 and 85Baseline, Day 29, 57, 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.

Number of Treatment-Emergent Adverse Events (TEAEs) by SeverityDay 1 up to Day 141

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.

Number of Participants With Clinically Significant Changes in Vital Signs and Electrocardiogram (ECG) ParametersDay 1 up to Day 141

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).

Trial Locations

Locations (44)

Kendall South Medical Center

🇺🇸

Miami, Florida, United States

Texas Center for Drug Development, Inc.

🇺🇸

Houston, Texas, United States

Heartland Research Associates, LLC

🇺🇸

Wichita, Kansas, United States

Vince and Associates Clinical Research

🇺🇸

Overland Park, Kansas, United States

Lynn Health Science Institute

🇺🇸

Oklahoma City, Oklahoma, United States

Oklahoma Cardiovascular Research Group (OCRG)

🇺🇸

Oklahoma City, Oklahoma, United States

Oklahoma Heart Hospital Physicians

🇺🇸

Oklahoma City, Oklahoma, United States

Oklahoma Heart Hospital

🇺🇸

Oklahoma City, Oklahoma, United States

Diablo Clinical Research, Inc.

🇺🇸

Walnut Creek, California, United States

Orange County Research Center

🇺🇸

Tustin, California, United States

Innovative Research of West Florida, Inc.

🇺🇸

Clearwater, Florida, United States

Avail Clinical Research, LLC

🇺🇸

DeLand, Florida, United States

In Vivo Clinical Research, Inc.

🇺🇸

Doral, Florida, United States

Jacksonville Center for Clinical Research

🇺🇸

Jacksonville, Florida, United States

North Georgia Internal Medicine

🇺🇸

Woodstock, Georgia, United States

North Georgia Clinical Research

🇺🇸

Woodstock, Georgia, United States

L-MARC Research Center

🇺🇸

Louisville, Kentucky, United States

Commonwealth Biomedical Research, LLC

🇺🇸

Madisonville, Kentucky, United States

Maine Research Associates

🇺🇸

Auburn, Maine, United States

Infinity Medical Research

🇺🇸

North Dartmouth, Massachusetts, United States

The Center for Pharmaceutical Research, P.C.

🇺🇸

Kansas City, Missouri, United States

Saint Luke's Hospital

🇺🇸

Kansas City, Missouri, United States

Saint Luke's Lipid and Diabetes Research Center

🇺🇸

Kansas City, Missouri, United States

North Carolina Clinical Research

🇺🇸

Raleigh, North Carolina, United States

New Mexico Clinical Research & Osteoporosis Center, Incorporated

🇺🇸

Albuquerque, New Mexico, United States

PMG Research of Salisbury

🇺🇸

Salisbury, North Carolina, United States

Perelman Center for Advanced Medicine

🇺🇸

Philadelphia, Pennsylvania, United States

Translational Research Center

🇺🇸

Philadelphia, Pennsylvania, United States

Spartanburg Medical Research

🇺🇸

Spartanburg, South Carolina, United States

New Orleans Center for Clinical Research

🇺🇸

Knoxville, Tennessee, United States

Volunteer Research Group

🇺🇸

Knoxville, Tennessee, United States

Paragon Research Center, LLC

🇺🇸

San Antonio, Texas, United States

Clinical Trials of Texas, Inc.

🇺🇸

San Antonio, Texas, United States

National Clinical Research - Norfolk, Inc.

🇺🇸

Norfolk, Virginia, United States

San Antonio Preventive & Diagnostic Medicine, PA

🇺🇸

San Antonio, Texas, United States

Diex Research Sherbrooke Inc.

🇨🇦

Sherbrooke, Quebec, Canada

The Medical Arts Health Research Group

🇨🇦

Kelowna, British Columbia, Canada

Centre de Recherche Clinique de Laval

🇨🇦

Laval, Quebec, Canada

Q & T Research Chicoutimi

🇨🇦

Chicoutimi, Quebec, Canada

Diex Research Montreal Inc.

🇨🇦

Montreal, Quebec, Canada

Clinique des Maladies Lipidiques de Quebec Inc.

🇨🇦

Quebec, Canada

National Clinical Research - Richmond, Inc.

🇺🇸

Richmond, Virginia, United States

Altoona Center for Clinical Research

🇺🇸

Duncansville, Pennsylvania, United States

Medex Healthcare Research, Inc.

🇺🇸

Saint Louis, Missouri, United States

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