Overview

This trial is active, not recruiting.

Condition hyperlipidemia
Treatments part a, atorvastatin, part a, placebo (administered orally), part b, evolocumab, part b, placebo (administered orally), part b, ezetimibe, part b, placebo (administered subcutaneously), part c, evolocumab
Phase phase 3
Sponsor Amgen
Start date December 2013
End date November 2015
Trial size 511 participants
Trial identifier NCT01984424, 20120332

Summary

The study is divided into 3 parts (A, B, C). Part A is a double-blind, placebo-controlled, two-period cross-over rechallenge of atorvastatin 20 mg. Part B is a 24-week double-blind, double-dummy comparison of evolocumab and ezetimibe. Part C is a 2-year open-label evolocumab extension. The primary hypothesis is that evolocumab will be well tolerated and will result in greater reduction of LDL-C than ezetimibe, defined by the mean percent change from baseline at Weeks 22 and 24 of Part B and percent change from baseline at Week 24 of Part B, in statin-intolerant hypercholesterolemic subjects.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Atorvastatin
part a, atorvastatin
Subjects will receive atorvastatin daily
part a, placebo (administered orally)
Subjects will receive oral placebo daily
(Placebo Comparator)
Placebo
part a, atorvastatin
Subjects will receive atorvastatin daily
part a, placebo (administered orally)
Subjects will receive oral placebo daily
(Experimental)
Evolocumab
part b, evolocumab
Subjects will receive subcutaneous evolocumab every month
part b, placebo (administered orally)
Subjects will receive oral placebo every day
(Active Comparator)
Ezetimbe
part b, ezetimibe
Subjects will receive oral ezetimibe daily
part b, placebo (administered subcutaneously)
Subjects will receive subcutaneous placebo every month.
(Experimental)
Evolocumab
part c, evolocumab
Subjects will receive subcutaneous evolocumab every 2 weeks or monthly

Primary Outcomes

Measure
Mean percent change from baseline in low density lipoprotein-cholesterol
time frame: 22 and 24 Weeks
Percent change from baseline in low density lipoprotein-cholesterol
time frame: 24 Weeks

Secondary Outcomes

Measure
Mean change from baseline in low density lipoprotein-cholesterol
time frame: 22 and 24 Weeks
Change from baseline in low density lipoprotein-cholesterol
time frame: 24 Weeks
Mean low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L])
time frame: 22 and 24 Weeks
Low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L])
time frame: 24 Weeks
Mean percent change from baseline in total cholesterol
time frame: 22 and 24 Weeks
Percent change from baseline in total cholesterol
time frame: 24 Weeks
Mean percent change from baseline in non-high density lipoprotein-cholesterol
time frame: 22 and 24 Weeks
Percent change from baseline in non-high density lipoprotein-cholesterol
time frame: 24 Weeks
Mean percent change from baseline in apolipoprotein B
time frame: 22 and 24 Weeks
Percent change from baseline in apolipoprotein B
time frame: 24 Weeks
Mean percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio
time frame: 22 and 24 Weeks
Percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio
time frame: 24 Weeks
Mean percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio
time frame: 22 and 24 Weeks
Percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio
time frame: 24 Weeks
Mean percent change from baseline in lipoprotein (a)
time frame: 22 and 24 Weeks
Percent change from baseline in lipoprotein (a)
time frame: 24 Weeks
Mean percent change from baseline in triglycerides
time frame: 22 and 24 Weeks
Percent change from baseline in triglycerides
time frame: 24 Weeks
Mean percent change from baseline in high density lipoprotein-cholesterol
time frame: 22 and 24 Weeks
Percent change from baseline in high density lipoprotein-cholesterol
time frame: 24 Weeks
Mean percent change from baseline in very low density lipoprotein-cholesterol
time frame: 22 and 24 Weeks
Percent change from baseline in very low density lipoprotein-cholesterol
time frame: 24 Weeks

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

Inclusion Criteria: - Male or female ≥ 18 to ≤ 80 years of age - Subject not at LDL-C goal - History of statin intolerance - Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks - Fasting triglycerides ≤ 400 mg/dL Exclusion Criteria: - NYHA III or IV heart failure - Uncontrolled cardiac arrhythmia - Uncontrolled hypertension - Type 1 diabetes - Poorly controlled type 2 diabetes - Uncontrolled hypothyroidism or hyperthyroidism

Additional Information

Official title A Double-blind, Randomized, Multicenter Study to Evaluate the Safety and Efficacy of Evolocumab, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor Due to Muscle Related Side Effects
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Amgen.