Clinical trial NCT02634580: Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-4
Official title: A Double-blind, Randomized, Multicenter Study to Evaluate the Safety and Efficacy of Evolocumab, Compared With Ezetimibe, in Hypercholesterolemic Japanese Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor Due to Muscle Related Side Effects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Keywords: Japanese
High cholesterol
Treatment of high cholesterol
Lowering cholesterol
Lowering high cholesterol
Hypercholesterolemia
Statin intolerant
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2015-12-18
Enrollment: 61
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study was to evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin.

Detailed description: After screening participants who met all inclusion/exclusion criteria were randomized with an allocation ratio of 2:2:1:1 into 4 groups: evolocumab (AMG 145) 420 mg administered by subcutaneous injection monthly and placebo pill daily; evolocumab 140 mg administered by subcutaneous injection every two weeks and placebo pill by mouth daily; placebo 420 mg administered by subcutaneous injection monthly and ezetimibe 10 mg pill daily; placebo 140 mg administered subcutaneous injection every two weeks and ezetimibe 10 mg pill daily. Randomization was stratified by screening LDL-C level and baseline statin use. Participants on low or atypical statin dose therapy must have been on a stable dose for at least 4 weeks prior to screening and throughout the blinded portion of the study; the dose could not be adjusted during screening and for the duration of the study. After Week 12, ezetimibe was discontinued and participants moved to an open-label dose of evolocumab administered by subcutaneous injection either every two weeks or monthly and their standard of care.

Eligibility criteria: Inclusion Criteria:

* Male or female ≥ 20 to ≤ 80 years of age
* Japanese by self-identification
* Not on a statin or on a low dose statin with stable dose for at least 4 weeks.
* Subject not at LDL-C goal
* History of statin intolerance to at least 2 statins
* Lipid lowering therapy has been stable prior to screening for at least 4 weeks
* Fasting triglycerides ≤ 400 mg/dL

Exclusion Criteria:

* New York Heart Association (NYHA) III or IV heart failure
* Uncontrolled cardiac arrhythmia
* Uncontrolled hypertension
* Type 1 diabetes
* Poorly controlled type 2 diabetes
* Uncontrolled hypothyroidism or hyperthyroidism

Primary outcomes:
measure: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
timeFrame: Baseline and week 12
Secondary outcomes:
measure: Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
timeFrame: Baseline and weeks 10 and 12
measure: Change From Baseline in LDL-C at Week 12
timeFrame: Baseline and week 12
measure: Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL
timeFrame: Weeks 10 and 12
measure: Percentage of Participants Who Achieved a LDL-C of Less Than 70 mg/dL at Week 12
timeFrame: Week 12
measure: Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12
timeFrame: Baseline and weeks 10 and 12
measure: Percent Change From Baseline in Total Cholesterol at Week 12
timeFrame: Baseline and week 12
measure: Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12
timeFrame: Baseline and weeks 10 and 12
measure: Percent Change From Baseline in Non-HDL-C at Week 12
timeFrame: Baseline and week 12
measure: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in Apolipoprotein B at Week 12
timeFrame: Baseline and week 12
measure: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12
timeFrame: Baseline and weeks 10 and 12
measure: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
timeFrame: Baseline and week 12
measure: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12
timeFrame: Baseline and weeks 10 and 12
measure: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12
timeFrame: Baseline and week 12
measure: Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12
timeFrame: Baseline and weeks 10 and 12
measure: Percent Change From Baseline in Lipoprotein(a) at Week 12
timeFrame: Baseline and week 12
measure: Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
timeFrame: Baseline and weeks 10 and 12
measure: Percent Change From Baseline in Triglycerides at Week 12
timeFrame: Baseline and week 12
measure: Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12
timeFrame: Baseline and weeks 10 and 12
measure: Percent Change From Baseline in HDL-C at Week 12
timeFrame: Baseline and week 12
measure: Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12
timeFrame: Baseline and weeks 10 and 12
measure: Percent Change From Baseline in VLDL-C at Week 12
timeFrame: Baseline and week 12
Other outcomes:
Locations:
city: Nagoya-shi
country: Japan
facility: Research Site
state: Aichi
city: Nagoya-shi
country: Japan
facility: Research Site
state: Aichi
city: Chiba-shi
country: Japan
facility: Research Site
state: Chiba
city: Kisarazu-shi
country: Japan
facility: Research Site
state: Chiba
city: Matsudo-shi
country: Japan
facility: Research Site
state: Chiba
city: Chikushino-shi
country: Japan
facility: Research Site
state: Fukuoka
city: Koga-shi
country: Japan
facility: Research Site
state: Fukuoka
city: Sukagawa-shi
country: Japan
facility: Research Site
state: Fukushima
city: Sukagawa-shi
country: Japan
facility: Research Site
state: Fukushima
city: Hiroshima-shi
country: Japan
facility: Research Site
state: Hiroshima
city: Kobe-shi
country: Japan
facility: Research Site
state: Hyogo
city: Koga-shi
country: Japan
facility: Research Site
state: Ibaraki
city: Kahoku-gun
country: Japan
facility: Research Site
state: Ishikawa
city: Kanazawa-shi
country: Japan
facility: Research Site
state: Ishikawa
city: Komatsu-shi
country: Japan
facility: Research Site
state: Ishikawa
city: Morioka-shi
country: Japan
facility: Research Site
state: Iwate
city: Morioka-shi
country: Japan
facility: Research Site
state: Iwate
city: Kagoshima-shi
country: Japan
facility: Research Site
state: Kagoshima
city: Yokohama-shi
country: Japan
facility: Research Site
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Research Site
state: Kumamoto
city: Kumamoto-shi
country: Japan
facility: Research Site
state: Kumamoto
city: Kyoto-shi
country: Japan
facility: Research Site
state: Kyoto
city: Ohsaki-shi
country: Japan
facility: Research Site
state: Miyagi
city: Nakagami-gun
country: Japan
facility: Research Site
state: Okinawa
city: Osaka-shi
country: Japan
facility: Research Site
state: Osaka
city: Osaka-Shi
country: Japan
facility: Research Site
state: Osaka
city: Fujimi-shi
country: Japan
facility: Research Site
state: Saitama
city: Iruma-gun
country: Japan
facility: Research Site
state: Saitama
city: Kawaguchi-shi
country: Japan
facility: Research Site
state: Saitama
city: Hamamatsu-shi
country: Japan
facility: Research Site
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: Research Site
state: Tokyo
city: Chuo-ku
country: Japan
facility: Research Site
state: Tokyo
city: Higashiyamato-shi
country: Japan
facility: Research Site
state: Tokyo
city: Musashino-shi
country: Japan
facility: Research Site
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Research Site
state: Tokyo
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Koba S, Inoue I, Cyrille M, Lu C, Inomata H, Shimauchi J, Kajinami K. Evolocumab vs. Ezetimibe in Statin-Intolerant Hyperlipidemic Japanese Patients: Phase 3 GAUSS-4 Trial. J Atheroscler Thromb. 2020 May 1;27(5):471-484. doi: 10.5551/jat.50963. Epub 2019 Nov 21.