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The primary objective is to evaluate the effect of 12 weeks of subcutaneous evolocumab every 2 weeks or every 4 weeks, compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) when used in addition to statin therapy in Japanese adults with hypercholesterolemia and high cardiovascular risk.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo Q2W | Placebo Comparator | Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. |
|
| Placebo Q4W | Placebo Comparator | Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks. |
|
| Evolocumab 70 mg Q2W | Experimental | Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. |
|
| Evolocumab 140 mg Q2W | Experimental | Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. |
|
| Evolocumab 280 mg Q4W | Experimental | Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
|
| Evolocumab 420 mg Q4W |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Evolocumab | Biological | Administered by subcutaneous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was measured using ultracentrifugation. | Baseline and Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was measured using ultracentrifugation. | Baseline and Week 12 |
| Percentage of Participants With an LDL-C Response at Week 12 |
Not provided
Inclusion Criteria: Japanese adult, on statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks, fasting LDL-C greater than or equal to 115 mg/dL (3.0 mmol/L), fasting triglycerides less than or equal to 400 mg/dL (4.5 mmol/L); Exclusion Criteria: New York Heart Association (NYHA) class III or IV, poorly controlled hypertension, recently diagnosed or poorly controlled type 2 diabetes, last known left ventricular ejection fraction < 30%, myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), stroke, planned cardiac surgery or revascularization within 6 months of randomization, uncontrolled cardiac arrhythmia.
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Nagoya | Aichi-ken | 454-0933 | Japan | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28367845 | Background | Hirayama A, Yamashita S, Inomata H, Kassahun H, Cyrille M, Ruzza A, Yoshida M, Kiyosue A, Ma Y, Teramoto T. One-Year Efficacy and Safety of Evolocumab in Japanese Patients - A Pooled Analysis From the Open-Label Extension OSLER Studies. Circ J. 2017 Jun 23;81(7):1029-1035. doi: 10.1253/circj.CJ-16-1016. Epub 2017 Mar 29. | |
| 28249876 |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
Not provided
Randomization was stratified by screening LDL-C level (< 130 mg/dL [3.4 mmol/L] vs
≥ 130 mg/dL) and by diagnosis of heterozygous familial hypercholesterolemia (HeFH) (yes vs no).
Japanese men or women ≥ 20 to ≤ 80 years of age and who were at high risk for cardiovascular events, on a stable dose of an approved statin (with or without ezetimibe) and fasting low-density lipoprotein cholesterol (LDL-C) ≥ 115 mg/dL.
First patient enrolled on 10 July 2012; last patient enrolled 19 February 2013.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo Q2W | Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. |
| FG001 | Placebo Q4W | Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
|
|
| Placebo | Other | Administered by subcutaneous injection |
|
An LDL-C response was defined as LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12. LDL-C was measured using ultracentrifugation.
| Week 12 |
| Percent Change From Baseline to Week 12 in Non-HDL-C | Baseline and Week 12 |
| Percent Change From Baseline to Week 12 in Apolipoprotein B | Baseline and Week 12 |
| Percent Change From Baseline to Week 12 in VLDL-C | Baseline and Week 12 |
| Percent Change From Baseline to Week 12 in Total Cholesterol/HDL-C Ratio | Baseline and Week 12 |
| Percent Change From Baseline to Week 12 in Apolipoprotein B/Apolipoprotein A-1 Ratio | Baseline and Week 12 |
| Nagoya |
| Aichi-ken |
| 455-8530 |
| Japan |
| Research Site | Nagoya | Aichi-ken | 462-0825 | Japan |
| Research Site | Fukui-shi | Fukui | 910-0067 | Japan |
| Research Site | Fukui-shi | Fukui | 910-0803 | Japan |
| Research Site | Fukui-shi | Fukui | 910-0837 | Japan |
| Research Site | Kasuga-shi | Fukuoka | 816-0864 | Japan |
| Research Site | Gifu | Gifu | 500-8384 | Japan |
| Research Site | Fujioka-shi | Gunma | 375-0015 | Japan |
| Research Site | Maebashi | Gunma | 371-0022 | Japan |
| Research Site | Maebashi | Gunma | 371-0046 | Japan |
| Research Site | Takasaki-shi | Gunma | 370-0829 | Japan |
| Research Site | Kawanishi | Hyōgo | 666-0125 | Japan |
| Research Site | Kobe | Hyōgo | 657-0068 | Japan |
| Research Site | Hitachi-shi | Ibaraki | 317-0077 | Japan |
| Research Site | Koga-shi | Ibaraki | 306-0041 | Japan |
| Research Site | Mito | Ibaraki | 311-4198 | Japan |
| Research Site | Komatsu-shi | Ishikawa-ken | 923-8560 | Japan |
| Research Site | Takamatsu | Kagawa-ken | 760-8557 | Japan |
| Research Site | Kochi | Kochi | 781-8555 | Japan |
| Research Site | Kumamoto | Kumamoto | 860-8556 | Japan |
| Research Site | Kyoto | Kyoto | 613-0911 | Japan |
| Research Site | Kyoto | Kyoto | 615-8125 | Japan |
| Research Site | Ina-shi | Nagano | 396-8555 | Japan |
| Research Site | Matsumoto-shi | Nagano | 390-0848 | Japan |
| Research Site | Suwa-shi | Nagano | 392-8510 | Japan |
| Research Site | Ibaraki-shi | Osaka | 567-0876 | Japan |
| Research Site | Suita-shi | Osaka | 565-0871 | Japan |
| Research Site | Toyonaka-shi | Osaka | 560-0082 | Japan |
| Research Site | Hanyu-shi | Saitama | 348-8505 | Japan |
| Research Site | Sayama-shi | Saitama | 350-1305 | Japan |
| Research Site | Toda-shi | Saitama | 335-0023 | Japan |
| Research Site | Ōtsu | Shiga | 520-0113 | Japan |
| Research Site | Bunkyo-ku | Tokyo | 113-8421 | Japan |
| Research Site | Bunkyo-ku | Tokyo | 113-8519 | Japan |
| Research Site | Chiyoda-ku | Tokyo | 101-0041 | Japan |
| Research Site | Chuo-ku | Tokyo | 103-0027 | Japan |
| Research Site | Hachioji-shi | Tokyo | 192-0918 | Japan |
| Research Site | Itabashi-ku | Tokyo | 173-8610 | Japan |
| Research Site | Shinagawa-ku | Tokyo | 141-0001 | Japan |
| Research Site | Taito-ku | Tokyo | 111-0052 | Japan |
| Research Site | Toshima-ku | Tokyo | 171-0021 | Japan |
| Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1. |
| 29353350 | Background | Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7. |
| FG002 | Evolocumab 70 mg Q2W | Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. |
| FG003 | Evolocumab 140 mg Q2W | Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. |
| FG004 | Evolocumab 280 mg Q4W | Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| FG005 | Evolocumab 420 mg Q4W | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| Received Treatment |
|
| COMPLETED |
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| NOT COMPLETED |
|
|
Full analysis set (all randomized participants who received at least 1 dose of investigational product).
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo Q2W | Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. |
| BG001 | Placebo Q4W | Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks. |
| BG002 | Evolocumab 70 mg Q2W | Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. |
| BG003 | Evolocumab 140 mg Q2W | Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. |
| BG004 | Evolocumab 280 mg Q4W | Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| BG005 | Evolocumab 420 mg Q4W | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| ||||||||||||||||
| Stratification Factor: LDL Level | Number | participants |
| ||||||||||||||||
| Stratification Factor: Diagnosis of Heterozygous Familial Hypercholesterolemia (HeFH) | Number | participants |
| ||||||||||||||||
| LDL-C Concentration | LDL-C was measured using ultracentrifugation. | Mean | Standard Deviation | mg/dL |
| ||||||||||||||
| Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| Apolipoprotein B Concentration | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| Very Low-Density Lipoprotein Cholesterol (VLDL-C) Concentration | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| Total Cholesterol/HDL-C Ratio | Mean | Standard Deviation | ratio |
| |||||||||||||||
| Apolipoprotein B/Apolipoprotein A-1 Ratio | Mean | Standard Deviation | ratio |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was measured using ultracentrifugation. | Full analysis set; missing ultracentrifugation (UC) LDL-C at Week 12 was imputed using last observation carried forward (LOCF) and calculated LDL-C. | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was measured using ultracentrifugation. | Full analysis set; missing data were imputed using LOCF. | Posted | Least Squares Mean | Standard Error | mg/dL | Baseline and Week 12 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With an LDL-C Response at Week 12 | An LDL-C response was defined as LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12. LDL-C was measured using ultracentrifugation. | Full analysis set | Posted | Number | percentage of participants | Week 12 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline to Week 12 in Non-HDL-C | Full analysis set; missing data were imputed using LOCF. | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline to Week 12 in Apolipoprotein B | Full analysis set; missing data were imputed using LOCF. | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline to Week 12 in VLDL-C | Full analysis set; missing data were imputed using LOCF. | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline to Week 12 in Total Cholesterol/HDL-C Ratio | Full analysis set; missing data were imputed using LOCF. | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline to Week 12 in Apolipoprotein B/Apolipoprotein A-1 Ratio | Full analysis set; missing data were imputed using LOCF. | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
|
12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo Q2W | Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. | 0 | 52 | 6 | 52 | ||
| EG001 | Placebo Q4W | Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks. | 0 | 50 | 6 | 50 | ||
| EG002 | Evolocumab Q2W 70 MG | Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. | 0 | 49 | 10 | 49 | ||
| EG003 | Evolocumab Q2W 140 MG | Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. | 1 | 52 | 9 | 52 | ||
| EG004 | Evolocumab Q4W 280 MG | Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | 1 | 51 | 12 | 51 | ||
| EG005 | Evolocumab Q4W 420 MG | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | 2 | 53 | 8 | 53 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fracture | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Carcinoid tumour of the caecum | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
| |
| Arteriosclerosis | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 |
| ID | Term |
|---|---|
| D006937 | Hypercholesterolemia |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C577155 | evolocumab |
Not provided
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| Male |
|
| Asian |
|
| Black or African American |
|
| Native Hawaiian or Other Pacific Islander |
|
| White |
|
| ≥ 130 mg/dL |
|
| Yes |
|
| Superiority or Other |
| The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist. | ANCOVA | The ANCOVA model included treatment group and stratification factor of screening LDL-C level. | <0.001 | Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05. | LS Mean Treatment Difference | -52.85 | Standard Error of the Mean | 3.03 | 2-Sided | 95 | -58.84 | -46.86 | Placebo is the reference | Superiority or Other |
| The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist. | ANCOVA | The ANCOVA model included treatment group and stratification factor of screening LDL-C level. | <0.001 | Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05. | LS Mean Treatment Difference | -63.94 | Standard Error of the Mean | 3.18 | 2-Sided | 95 | -70.23 | -57.66 | Placebo is the reference | Superiority or Other |
| The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist. | ANCOVA | The ANCOVA model included treatment group and stratification factor of screening LDL-C level. | <0.001 | Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05. | LS Mean Treatment Difference | -58.16 | Standard Error of the Mean | 3.21 | 2-Sided | 95 | -64.51 | -51.81 | Placebo is the reference | Superiority or Other |
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| OG005 | Evolocumab 420 mg Q4W | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
|
|
|
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| OG005 | Evolocumab 420 mg Q4W | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
|
|
|
| OG005 | Evolocumab 420 mg Q4W | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
|
|
|
| OG005 | Evolocumab 420 mg Q4W | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
|
|
|
| OG005 | Evolocumab 420 mg Q4W | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
|
|
|
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
| OG005 | Evolocumab 420 mg Q4W | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
|
|
|
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
| OG005 | Evolocumab 420 mg Q4W | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
|
|
|