Hypercholesterolemia and High Risk for Cardiovascular EventsPhase 2AMG145NCT01652703

A Study to Evaluate Tolerability and Efficacy of Evolocumab (AMG 145) in Japanese Subjects

A Phase 2 study testing Evolocumab in people with Hypercholesterolemia and High Risk for Cardiovascular Events, run by Amgen at 42 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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… Read more about this study

Who is it for?: Ages 20 to 80 years
Conditions the study is for: Hypercholesterolemia and High Risk for Cardiovascular Events
What is being tested?: Evolocumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 310 participants
Where: 42 sitesJapan
Study dates: 10 Jul 2012to 14 May 2013
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

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.

Trial locations and contacts

42 sites in 1 country.

City, postcode or hospital

42 sites in 1 country

Japan42 sites

Research Site
Bunkyo-ku, Tokyo, 113-8421
Research Site
Bunkyo-ku, Tokyo, 113-8519
Research Site
Chiyoda-ku, Tokyo, 101-0041
Research Site
Chuo-ku, Tokyo, 103-0027
Research Site
Fujioka-shi, Gunma, 375-0015
Research Site
Fukui-shi, Fukui, 910-0067
Research Site
Fukui-shi, Fukui, 910-0803
Research Site
Fukui-shi, Fukui, 910-0837
Research Site
Gifu, Gifu, 500-8384
Research Site
Hachioji-shi, Tokyo, 192-0918
Research Site
Hanyu-shi, Saitama, 348-8505
Research Site
Hitachi-shi, Ibaraki, 317-0077
Research Site
Ibaraki-shi, Osaka, 567-0876
Research Site
Ina-shi, Nagano, 396-8555
Research Site
Kasuga-shi, Fukuoka, 816-0864
Research Site
Kawanishi, Hyōgo, 666-0125
Research Site
Kobe, Hyōgo, 657-0068
Research Site
Kochi, Kochi, 781-8555
Research Site
Koga-shi, Ibaraki, 306-0041
Research Site
Komatsu-shi, Ishikawa-ken, 923-8560
Research Site
Kumamoto, Kumamoto, 860-8556
Research Site
Kyoto, Kyoto, 613-0911
Research Site
Kyoto, Kyoto, 615-8125
Research Site
Maebashi, Gunma, 371-0022
Research Site
Maebashi, Gunma, 371-0046
Research Site
Matsumoto-shi, Nagano, 390-0848
Research Site
Mito, Ibaraki, 311-4198
Research Site
Nagoya, Aichi-ken, 454-0933
Research Site
Nagoya, Aichi-ken, 455-8530
Research Site
Nagoya, Aichi-ken, 462-0825
Research Site
Ōtsu, Shiga, 520-0113
Research Site
Sayama-shi, Saitama, 350-1305
Research Site
Shinagawa-ku, Tokyo, 141-0001
Research Site
Suita-shi, Osaka, 565-0871
Research Site
Suwa-shi, Nagano, 392-8510
Research Site
tabashi City, Tokyo, 173-8610
Research Site
Taito-ku, Tokyo, 111-0052
Research Site
Takamatsu, Kagawa-ken, 760-8557
Research Site
Takasaki-shi, Gunma, 370-0829
Research Site
Toda-shi, Saitama, 335-0023
Research Site
Toshima-ku, Tokyo, 171-0021
Research Site
Toyonaka-shi, Osaka, 560-0082

Other trials in Japan

About this study

Official title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Stable Statin Therapy in Japanese Subjects With Hypercholesterolemia and High Cardiovascular Risk

Conditions: Hypercholesterolemia and High Risk for Cardiovascular Events
Being tested: Evolocumab, Placebo
Keywords: Japanese, hypercholesterolemia, high risk for cardiovascular events
Medical subject headings: Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EvolocumabBiological
Also called AMG 145, Repatha
Administered by subcutaneous injection
PlaceboOther
Administered by subcutaneous injection

Study groups in NCT01652703
Study group	Role	What they receive
Placebo Q2W	Placebo comparator	Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. Receives: Other: Placebo
Placebo Q4W	Placebo comparator	Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks. Receives: Other: Placebo
Evolocumab 70 mg Q2W	Experimental	Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Receives: Biological: Evolocumab
Evolocumab 140 mg Q2W	Experimental	Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Receives: Biological: Evolocumab
Evolocumab 280 mg Q4W	Experimental	Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Receives: Biological: Evolocumab
Evolocumab 420 mg Q4W	Experimental	Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Receives: Biological: Evolocumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
LDL-C was measured using ultracentrifugation.
Measured: Baseline and Week 12

Secondary outcomes (7)

Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
LDL-C was measured using ultracentrifugation.
Measured: Baseline and Week 12
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.
Measured: Week 12
Percent Change From Baseline to Week 12 in Non-HDL-C
Measured: Baseline and Week 12
Percent Change From Baseline to Week 12 in Apolipoprotein B
Measured: Baseline and Week 12
Percent Change From Baseline to Week 12 in VLDL-C
Measured: Baseline and Week 12
Percent Change From Baseline to Week 12 in Total Cholesterol/HDL-C Ratio
Measured: Baseline and Week 12
Percent Change From Baseline to Week 12 in Apolipoprotein B/Apolipoprotein A-1 Ratio
Measured: Baseline and Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Jul 201214 May 2013

First posted30 Jul 2012 (estimated)
Study start10 Jul 2012
Primary completion14 May 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Hypercholesterolemia and High Risk for Cardiovascular EventsStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 310 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01652703
Sponsor's protocol ID: 20110231
Acronym: AMG145
Status last verified: Nov 2018
First submitted: 26 Jul 2012
Last updated: 28 Nov 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 28367845
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.
PubMed 28249876
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.
PubMed 29353350

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Test 2 Treat: Can we Improve the Testing and Treatment of High Cholesterol in Patients Who Have Been Hospitalized for a Cardiac Event by Providing Education to Doctors and Patients?
ASCVD, LDL-C

All Hypercholesterolemia and High Risk for Cardiovascular Events trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Stable Statin Therapy in Japanese Subjects With Hypercholesterolemia and High Cardiovascular Risk
ClinicalTrials.gov ID: NCT01652703
Acronym / sponsor ID: AMG145 / 20110231
Conditions: Hypercholesterolemia and High Risk for Cardiovascular Events
Keywords: Japanese, hypercholesterolemia, high risk for cardiovascular events
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 310 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 10 Jul 2012 (actual)
Primary completion: 14 May 2013 (actual)
First posted: 30 Jul 2012 (estimated)
Results: Posted 5 Oct 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 6

Arm	Type	Receives
Placebo Q2W	Placebo comparator	Other: PlaceboParticipants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
Placebo Q4W	Placebo comparator	Other: PlaceboParticipants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Evolocumab 70 mg Q2W	Experimental	Biological: EvolocumabParticipants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 140 mg Q2W	Experimental	Biological: EvolocumabParticipants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 280 mg Q4W	Experimental	Biological: EvolocumabParticipants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 420 mg Q4W	Experimental	Biological: EvolocumabParticipants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Who may qualify

Ages: 20 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EvolocumabAlso: AMG 145, RepathaAdministered by subcutaneous injection	Biological	Evolocumab 140 mg Q2W, Evolocumab 280 mg Q4W, Evolocumab 420 mg Q4W, Evolocumab 70 mg Q2W
PlaceboAdministered by subcutaneous injection	Other	Placebo Q2W, Placebo Q4W

Primary outcome

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time frame: Baseline and Week 12
LDL-C was measured using ultracentrifugation.

7 secondary outcomes

Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time frame: Baseline and Week 12
Percentage of Participants With an LDL-C Response at Week 12
Time frame: Week 12
Percent Change From Baseline to Week 12 in Non-HDL-C
Time frame: Baseline and Week 12
Percent Change From Baseline to Week 12 in Apolipoprotein B
Time frame: Baseline and Week 12
Percent Change From Baseline to Week 12 in VLDL-C
Time frame: Baseline and Week 12
Percent Change From Baseline to Week 12 in Total Cholesterol/HDL-C Ratio
Time frame: Baseline and Week 12
Percent Change From Baseline to Week 12 in Apolipoprotein B/Apolipoprotein A-1 Ratio
Time frame: Baseline and Week 12

Results and safety

Results posted to the registry on 5 Oct 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo Q2W	52	52
Placebo Q4W	51	50
Evolocumab 70 mg Q2W	50	47
Evolocumab 140 mg Q2W	52	50
Evolocumab 280 mg Q4W	52	51
Evolocumab 420 mg Q4W	53	51

Primary outcome: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

Time frame: Baseline and Week 12. Least squares mean (Standard Error). Unit: percent change

Measure	Placebo Q2W n = 52	Placebo Q4W n = 50	Evolocumab 70 mg Q2W n = 49	Evolocumab 140 mg Q2W n = 52	Evolocumab 280 mg Q4W n = 51	Evolocumab 420 mg Q4W n = 53
Value	-2.71 (2.16)	0.05 (2.32)	-55.56 (2.23)	-71.32 (2.16)	-58.10 (2.33)	-63.89 (2.27)

Placebo Q2W vs Evolocumab 140 mg Q2W: LS Mean Treatment Difference: -68.61 (95% CI -74.51 to -62.71), p <0.001, ANCOVA
Placebo Q2W vs Evolocumab 70 mg Q2W: LS Mean Treatment Difference: -52.85 (95% CI -58.84 to -46.86), p <0.001, ANCOVA
Placebo Q4W vs Evolocumab 420 mg Q4W: LS Mean Treatment Difference: -63.94 (95% CI -70.23 to -57.66), p <0.001, ANCOVA

Population analysed: Full analysis set; missing ultracentrifugation (UC) LDL-C at Week 12 was imputed using last observation carried forward (LOCF) and calculated LDL-C.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Q2W	0 of 52 (0%)	6 of 52 (11.5%)	Not reported
Placebo Q4W	0 of 50 (0%)	6 of 50 (12%)	Not reported
Evolocumab Q2W 70 MG	0 of 49 (0%)	10 of 49 (20.4%)	Not reported
Evolocumab Q2W 140 MG	1 of 52 (1.9%)	9 of 52 (17.3%)	Not reported
Evolocumab Q4W 280 MG	1 of 51 (2%)	12 of 51 (23.5%)	Not reported
Evolocumab Q4W 420 MG	2 of 53 (3.8%)	8 of 53 (15.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 28367845Hirayama 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.
Background: PubMed 28249876Toth 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.
Background: PubMed 29353350Kasichayanula 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.
AmgenTrials clinical trials websiteLink provided by the sponsor.

Related trials for Hypercholesterolemia and High Risk for Cardiovascular Events

Recruiting
Test 2 Treat: Can we Improve the Testing and Treatment of High Cholesterol in Patients Who Have Been Hospitalized for a Cardiac Event by Providing Education to Doctors and Patients?
ASCVD, LDL-C

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

42 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Evolocumab in people with Hypercholesterolemia and High Risk for Cardiovascular Events, run by Amgen at 42 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01652703, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2018.

Trial summary

Key requirements

Trial locations and contacts

About this study

What participants receive

What is being measured

Timeline

Resources

More details

Publications

Study at a glance

Clinical summary

Study design

Who may qualify

Interventions

Primary outcome

Results and safety

Participant flow

Primary outcome: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

Adverse events

Research links

Related trials for Hypercholesterolemia and High Risk for Cardiovascular Events

Test 2 Treat: Can we Improve the Testing and Treatment of High Cholesterol in Patients Who Have Been Hospitalized for a Cardiac Event by Providing Education to Doctors and Patients?

Referral and contact

Questions about this trial

Participant flow

Primary outcome: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

Adverse events