Randomized Clinical Trial of Bococizumab (PF-04950615; RN316) in Subjects Who Are Intolerant to Statins

Study Overview
=================
Brief Summary
-----------------
This study is a multicenter, double blinded, active and placebo controlled randomized clinical trial to demonstrate a superior lipid lowering effect of Bococizumab (PF-04950615; RN316) compared to placebo in subjects who are statin intolerant.

Official Title
-----------------
A Phase 3, Double-blind, Double-dummy, Randomized, Placebo And Active Controlled, Parallel-group Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 In Subjects With Dyslipidemia Who Are Intolerant To Statins

Conditions
-----------------
Hyperlipidemia

Intervention / Treatment
-----------------
* Drug: Bococizumab (PF-04950615;RN316)
* Drug: Atorvastatin
* Other: Placebo for Bococizumab (PF-04950615;RN316)
* Other: Placebo for atorvastatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Hyperlipidemia Statin Intolerant Fasting LDL-C > = 70 mg/dL Fasting TG < = 400 mg/dL Exclusion Criteria: Pregnant or breastfeeding females Cardiovascular or cerebrovascular event or procedure within 90 days Severe or life-threatening adverse events with past use of statins Poorly controlled hypertension

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bococizumab (PF-04950615;RN316)<br>Bococizumab (PF-04950615;RN316) | Drug: Bococizumab (PF-04950615;RN316)<br>* 150 mg every 2 weeks by subcutaneous injection for 24 weeks<br>|
| Active Comparator: Atorvastatin<br> | Drug: Atorvastatin<br>* Atorvastatin PO QD<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo for Bococizumab (PF-04950615;RN316)<br>* 150 mg every 2 weeks by subcutaneous injection for 24 weeks<br>Other: Placebo for atorvastatin<br>* PO QD<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 |  | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Fasting Total Cholesterol (TC) at Weeks 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Weeks 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Weeks 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Weeks 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24 |  | Baseline, Week 24 | 
| Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Weeks 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Weeks 12 and 24 |  | Baseline, Week 12, 24 | 
| Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Weeks 12 and 24 |  | Baseline, Week 12, 24 | 
| Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting Triglycerides (TG) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Apolipoprotein B (ApoB) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Lipoprotein (A) (Lp[A]) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting Total Cholesterol (TC)/ High Density Lipoprotein Cholesterol (HDL-C) Ratio at Weeks 12 and 24 |  | Baseline, Week 12, 24 | 
| Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB)/Apolipoprotein A-I (ApoA-I) Ratio at Weeks 12 And 24 |  | Baseline, Week 12, 24 | 
| Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Weeks 12 and 24 |  | Week 12, 24 | 
| Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Weeks 12 and 24 |  | Week 12, 24 | 
| Plasma PF-04950615 Concentrations at Weeks 12 and 24 | Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ =0.4 micrograms per milliliter [mcg/mL]) to zero. Participants who received PF-04950615 150 mg were evaluable for this outcome measure. | Week 12 and 24 | 
| Number of Participants With Adverse Events Related to Type 1 and 3 Hypersensitivity Reactions, Injection Site Reactions, Myalgia, Myopathy, Creatinine Kinase (CK) and Liver Function Tests (LFT) Elevations |  | Baseline (Day 1) up to Week 30 | 
| Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | Participants with at least one positive ADA titer greater than or equal to (>=) 6.23 or positive nAb titer >=4.32 were reported. Titers are expressed as log2 reciprocal dilution at assay cutpoint. | Baseline up to Week 30 | 
| Anti-drug Antibody (ADA) and Neutralizing Anti-body (nAb) Titer Level in Participants Who Tested Positive for ADA and nAb Respectively | Titer levels of participants who tested positive for ADA and nAb are reported. Titers are expressed as log2 reciprocal dilution at assay cutpoint. | Week 4, 12, 24 and 30 (Follow-up) | 
| Percentage of Participants Discontinued Due to Myalgia, Myopathy, Creatinine Kinase (CK) and Liver Function Tests (LFT) Elevations |  | Baseline (Day 1) up to Week 30 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hyperlipidemia, statin intolerance