Efficacy, Safety, Tolerability And Actual Use Study Of Bococizumab And An Autoinjector (Pre-Filled Pen) In Subjects With Hyperlipidemia Or Dyslipidemia

Study Overview
=================
Brief Summary
-----------------
This study is a multicenter, randomized study in subjects with high cholesterol receiving statins to assess the efficacy to lower LDL-C, the safety, tolerability and actual use of bococizumab and an autoinjector (pre-filled pen).

Official Title
-----------------
A 12 Week, Phase 3, Double-blind, Randomized, Placebo-controlled, Parallel Group Study To Assess The Efficacy, Safety, Tolerability And Actual Use Of Bococizumab And An Autoinjector (Pre-filled Pen) In Subjects With Primary Hyperlipidemia Or Mixed Dyslipidemia

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

Intervention / Treatment
-----------------
* Biological: Bococizumab 150mg
* Biological: Bococizumab 75mg
* Biological: Bococizumab 150mg placebo
* Biological: Bococizumab 75mg placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Treated with a statin - Fasting LDL-C >=70mg/dL and triglycerides <=400mg/dL Exclusion Criteria: Pregnant or breastfeeding females - Cardiovascular or cerebrovascular event or procedures during the past 90 days - Congestive heart failure NYHA class IV - 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 150mg<br>Bococizumab 150mg autoinjector (pre-filled pen) | Biological: Bococizumab 150mg<br>* Bococizumab autoinjector (pre-filled pen) combination Product. 150mg every 2 weeks for 10 weeks, subcutaneous injection.<br>|
| Experimental: Bococizumab 75mg<br>Bococizumab 75mg autoinjector (pre-filled pen) | Biological: Bococizumab 75mg<br>* Bococizumab autoinjector (pre-filled pen) combination Product. 75mg every 2 weeks for 10 weeks, subcutaneous injection.<br>|
| Placebo Comparator: Bococizumab 150mg placebo<br>Bococizumab 150mg placebo autoinjector (pre-filled pen) | Biological: Bococizumab 150mg placebo<br>* Bococizumab placebo autoinjector (pre-filled pen) combination Product. 150mg placebo every 2 weeks for 10 weeks, subcutaneous injection.<br>|
| Placebo Comparator: Bococizumab 75mg placebo<br>Bococizumab 75mg autoinjector (pre-filled pen) | Biological: Bococizumab 75mg placebo<br>* Bococizumab placebo autoinjector (pre-filled pen) combination product. 75mg placebo every 2 weeks for 10 weeks, subcutaneous injection.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline at Week 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) Level for Bococizumab 150 mg Dose Group and Matched Placebo |  | Baseline, Week 12 | 
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 0 (Day 1) | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? | Week 0 (Day 1) | 
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 2 | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? | Week 2 | 
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 4 | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? | Week 4 | 
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 6 | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? | Week 6 | 
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 8 | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? | Week 8 | 
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 10 | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? | Week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? | Week 0 (Day 1), 2, 4, 6, 8, 10 | 
| Percentage of Injections That Met the Definition for Successful Assessment Using the Observer Assessment Tool (OAT) for Bococizumab 150 mg Dose, Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 4 and 8 | As per the OAT, a 'successful' injection was based on observer's response for the question - Was the administration successful?''. Observer's response being 'Yes' corresponded to a successful injection. | Week 0 (Day 1), 4, 8 | 
| Percent Change From Baseline at Week 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) Level for Bococizumab 75 mg Dose Group and Matched Placebo |  | Baseline, Week 12 | 
| Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 |  | Baseline, Week 12 | 
| Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12 |  | Baseline, Week 12 | 
| Percent Change From Baseline in Fasting Non- High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 |  | Baseline, Week 12 | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. Treatment-emergent were events between first dose of study drug up to the follow up visit (up to 18 weeks), that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. | Baseline up to 18 weeks | 
| Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. Participants with their ADA titer levels >=6.23 were considered as ADA positive and participants with their nAb titer level >=1.58 were considered as nAb positive. | Baseline up to 18 weeks | 
| Plasma Concentration of Bococizumab at Week 12 |  | Week 12 | 
| Plasma Concentration of Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) at Week 12 | PCSK9 is an enzyme encoded by the PCSK9 gene in humans on chromosome. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. | Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
mixed dyslipidemia