Clinical trial NCT01953328: Study of Low-Density Lipoprotein Cholesterol (LDL-C) Reduction Using Evolocumab (AMG 145) in Japanese Patients With Advanced Cardiovascular Risk
Official title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of Evolocumab (AMG 145) on LDL-C in Combination With Statin Therapy in Japanese Subjects With High Cardiovascular Risk and With Hyperlipidemia or Mixed Dyslipidemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperlipidemia or Mixed Dyslipidemia at High Risk for Cardiovascular Events
Keywords: Japanese, high cholesterol, LDL-C, High Cardiovascular Risk
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-09-30
Enrollment: 409
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
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 evolocumab administered every 2 weeks and once a month, compared with placebo, on percent change from baseline in LDL-C when used in combination with statin therapy in adults with high cardiovascular risk and with hyperlipidemia or mixed dyslipidemia.

Detailed description: After a screening and placebo run-in period, eligible patients were randomized in a 1:1 ratio to 1 of 2 open-label background statin treatments (atorvastatin 5 mg or 20 mg daily \[QD\]) and entered a 4-week lipid stabilization period. After the lipid stabilization period, eligible patients were randomized in a 1:1:1:1 ratio to investigational product (evolocumab or placebo) for the 12-week treatment period.

Both randomizations were stratified by subject diagnosis and lipid-lowering therapy as follows:

* current or prior diagnosis of heterozygous familial hypercholesterolemia (HeFH)
* no diagnosis of HeFH and receiving intensive lipid-lowering therapy
* no diagnosis of HeFH and receiving non-intensive lipid-lowering therapy. A participant was considered randomized into the study after successfully completing the screening period, meeting all inclusion/exclusion criteria including meeting final laboratory safety criteria, and undergoing both randomization procedures.

Eligibility criteria: Inclusion Criteria: Male or female, Japanese adult, 20-85 years of age; Subjects on stable dose of statin for greater than equal to 4 weeks; Fasting LDL-C greater than equal to 100 mg/dL; Fasting triglycerides less than equal to 400 mg/dL; Subject is at high risk for cardiovascular events. 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: 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 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 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 the Apolipoprotein B/Apolipoprotein A-1 Ratio 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 LDL-C < 70 mg/dL at Week 12
timeFrame: 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: Akita-shi
country: Japan
facility: Research Site
state: Akita
city: Noda-shi
country: Japan
facility: Research Site
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Research Site
state: Fukuoka
city: Fukuoka-shi
country: Japan
facility: Research Site
state: Fukuoka
city: Fukuoka-shi
country: Japan
facility: Research Site
state: Fukuoka
city: Kitakyusyu-shi
country: Japan
facility: Research Site
state: Fukuoka
city: Koriyama-shi
country: Japan
facility: Research Site
state: Fukushima
city: Koriyama-shi
country: Japan
facility: Research Site
state: Fukushima
city: Koriyama-shi
country: Japan
facility: Research Site
state: Fukushima
city: Koriyama-shi
country: Japan
facility: Research Site
state: Fukushima
city: Koriyama-shi
country: Japan
facility: Research Site
state: Fukushima
city: Maebashi-shi
country: Japan
facility: Research Site
state: Gunma
city: Takasaki-shi
country: Japan
facility: Research Site
state: Gunma
city: Sapporo-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Tsuchiura-shi
country: Japan
facility: Research Site
state: Ibaraki
city: Hanamaki-shi
country: Japan
facility: Research Site
state: Iwate
city: Morioka-shi
country: Japan
facility: Research Site
state: Iwate
city: Takamatsu-shi
country: Japan
facility: Research Site
state: Kagawa
city: Takamatsu-shi
country: Japan
facility: Research Site
state: Kagawa
city: Yokohama-shi
country: Japan
facility: Research Site
state: Kanagawa
city: Kyoto-shi
country: Japan
facility: Research Site
state: Kyoto
city: Sendai-shi
country: Japan
facility: Research Site
state: Miyagi
city: Sendai-shi
country: Japan
facility: Research Site
state: Miyagi
city: Sendai-shi
country: Japan
facility: Research Site
state: Miyagi
city: Tomigusuku-shi
country: Japan
facility: Research Site
state: Okinawa
city: Urasoe-shi
country: Japan
facility: Research Site
state: Okinawa
city: Ibaraki-shi
country: Japan
facility: Research Site
state: Osaka
city: Osaka-shi
country: Japan
facility: Research Site
state: Osaka
city: Toyonaka-shi
country: Japan
facility: Research Site
state: Osaka
city: Koshigaya-shi
country: Japan
facility: Research Site
state: Saitama
city: Kumagaya-shi
country: Japan
facility: Research Site
state: Saitama
city: Niiza-shi
country: Japan
facility: Research Site
state: Saitama
city: Arakawa-ku
country: Japan
facility: Research Site
state: Tokyo
city: Chiyoda-ku
country: Japan
facility: Research Site
state: Tokyo
city: Chiyoda-ku
country: Japan
facility: Research Site
state: Tokyo
city: Chofu-shi
country: Japan
facility: Research Site
state: Tokyo
city: Chuo-ku
country: Japan
facility: Research Site
state: Tokyo
city: Edogawa-ku
country: Japan
facility: Research Site
state: Tokyo
city: Hachioji-shi
country: Japan
facility: Research Site
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Research Site
state: Tokyo
city: Katsushika-ku
country: Japan
facility: Research Site
state: Tokyo
city: Koto-ku
country: Japan
facility: Research Site
state: Tokyo
city: Minato-ku
country: Japan
facility: Research Site
state: Tokyo
city: Minato-ku
country: Japan
facility: Research Site
state: Tokyo
city: Ota-ku
country: Japan
facility: Research Site
state: Tokyo
city: Setagaya-ku
country: Japan
facility: Research Site
state: Tokyo
city: Shibuya-ku
country: Japan
facility: Research Site
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Research Site
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Research Site
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Research Site
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Research Site
state: Tokyo
city: Toshima-ku
country: Japan
facility: Research Site
state: Tokyo
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: