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

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

Official Title
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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.

Conditions
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Hypercholesterolemia, Dyslipidemia

Intervention / Treatment
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* Biological: Placebo
* Drug: Statin
* Biological: PF-04950615 (RN316)
* Drug: Statin
* Biological: PF-04950615 (RN316)
* Drug: Statin
* Biological: PF-04950615 (RN316)
* Drug: Satin
* Biological: PF-04950615 (RN316)
* Drug: Statin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Treatment A<br> | Biological: Placebo<br>* Intravenous placebo monthly during treatment phase.<br>Drug: Statin<br>* 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.<br>|
| Experimental: Treatment B<br> | Biological: PF-04950615 (RN316)<br>* Intravenous 10mg/mL based on weight monthly during treatment phase.<br>Drug: Statin<br>* 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.<br>|
| Experimental: Treatment C<br> | Biological: PF-04950615 (RN316)<br>* Intravenous 10mg/mL based on weight monthly during treatment phase.<br>Drug: Statin<br>* 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.<br>|
| Experimental: Treatment D<br> | Biological: PF-04950615 (RN316)<br>* Intravenous 10mg/mL based on weight monthly during treatment phase.<br>Drug: Satin<br>* 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.<br>|
| Experimental: Treatment E<br> | Biological: PF-04950615 (RN316)<br>* Intravenous 10mg/mL based on weight monthly during treatment phase.<br>Drug: Statin<br>* 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.<br>|

What is the study measuring?
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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 <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, 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PF-04950615, RN316