Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-4 (GAUSS-4)

October 20, 2020 updated by: Amgen

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
61

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Aichi
      • Nagoya-shi, Aichi, Japan, 466-8560
        • Research Site
      • Nagoya-shi, Aichi, Japan, 466-8650
        • Research Site
    • Chiba
      • Chiba-shi, Chiba, Japan, 260-8677
        • Research Site
      • Kisarazu-shi, Chiba, Japan, 292-8535
        • Research Site
      • Matsudo-shi, Chiba, Japan, 271-0077
        • Research Site
    • Fukuoka
      • Chikushino-shi, Fukuoka, Japan, 818-8516
        • Research Site
      • Koga-shi, Fukuoka, Japan, 811-3195
        • Research Site
    • Fukushima
      • Sukagawa-shi, Fukushima, Japan, 962-0001
        • Research Site
      • Sukagawa-shi, Fukushima, Japan, 962-8503
        • Research Site
    • Hiroshima
      • Hiroshima-shi, Hiroshima, Japan, 734-8551
        • Research Site
    • Hyogo
      • Kobe-shi, Hyogo, Japan, 650-0017
        • Research Site
    • Ibaraki
      • Koga-shi, Ibaraki, Japan, 306-0041
        • Research Site
    • Ishikawa
      • Kahoku-gun, Ishikawa, Japan, 920-0293
        • Research Site
      • Kanazawa-shi, Ishikawa, Japan, 920-8650
        • Research Site
      • Komatsu-shi, Ishikawa, Japan, 923-8560
        • Research Site
    • Iwate
      • Morioka-shi, Iwate, Japan, 020-8505
        • Research Site
      • Morioka-shi, Iwate, Japan, 020-0866
        • Research Site
    • Kagoshima
      • Kagoshima-shi, Kagoshima, Japan, 890-8520
        • Research Site
    • Kanagawa
      • Yokohama-shi, Kanagawa, Japan, 245-8575
        • Research Site
    • Kumamoto
      • Kumamoto-shi, Kumamoto, Japan, 860-8556
        • Research Site
      • Kumamoto-shi, Kumamoto, Japan, 862-0976
        • Research Site
    • Kyoto
      • Kyoto-shi, Kyoto, Japan, 606-8507
        • Research Site
    • Miyagi
      • Ohsaki-shi, Miyagi, Japan, 989-6143
        • Research Site
    • Okinawa
      • Nakagami-gun, Okinawa, Japan, 901-2393
        • Research Site
    • Osaka
      • Osaka-Shi, Osaka, Japan, 553-0003
        • Research Site
      • Osaka-shi, Osaka, Japan, 530-0001
        • Research Site
    • Saitama
      • Fujimi-shi, Saitama, Japan, 354-0031
        • Research Site
      • Iruma-gun, Saitama, Japan, 350-0495
        • Research Site
      • Kawaguchi-shi, Saitama, Japan, 332-0012
        • Research Site
    • Shizuoka
      • Hamamatsu-shi, Shizuoka, Japan, 430-0929
        • Research Site
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-8655
        • Research Site
      • Chuo-ku, Tokyo, Japan, 103-0027
        • Research Site
      • Higashiyamato-shi, Tokyo, Japan, 207-0014
        • Research Site
      • Musashino-shi, Tokyo, Japan, 180-0022
        • Research Site
      • Shinagawa-ku, Tokyo, Japan, 142-8666
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Ezetimibe (Q2W)
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for 12 weeks. From week 12 participants received open-label evolocumab 140 mg subcutaneously once every 2 weeks until week 48.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • Repatha
  • AMG 145
Drug: Ezetimibe
Tablet for oral administration
Other Names:
  • Zetia
Drug: Placebo to Evolocumab
Administered by subcutaneous injection
Active Comparator: Ezetimibe (QM)
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for 12 weeks. From week 12 participants received open-label evolocumab 420 mg subcutaneously once a month until week 48.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • Repatha
  • AMG 145
Drug: Ezetimibe
Tablet for oral administration
Other Names:
  • Zetia
Drug: Placebo to Evolocumab
Administered by subcutaneous injection
Experimental: Evolocumab Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for 12 weeks. From week 12 participants received open-label evolocumab 140 mg subcutaneously once every 2 weeks until week 48.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • Repatha
  • AMG 145
Drug: Placebo Ezetimibe
Tablet for oral administration
Experimental: Evolocumab QM
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for 12 weeks. From week 12 participants received open-label evolocumab 420 mg subcutaneously once a month until week 48.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • Repatha
  • AMG 145
Drug: Placebo Ezetimibe
Tablet for oral administration

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12
Time Frame: Baseline and Weeks 10 and 12
For all efficacy endpoints the two dosing regimens (every 2 weeks and every month) for each treatment were pooled for analysis.
Baseline and Weeks 10 and 12
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time Frame: Baseline and week 12
Baseline and week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Time Frame: Baseline and Weeks 10 and 12
Baseline and Weeks 10 and 12
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time Frame: Baseline and weeks 10 and 12
Baseline and weeks 10 and 12
Change From Baseline in LDL-C at Week 12
Time Frame: Baseline and week 12
Baseline and week 12
Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12
Time Frame: Baseline and weeks 10 and 12
Baseline and weeks 10 and 12
Percent Change From Baseline in Non-HDL-C at Week 12
Time Frame: Baseline and week 12
Baseline and week 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Time Frame: Baseline and week 12
Baseline and week 12
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12
Time Frame: Baseline and weeks 10 and 12
Baseline and weeks 10 and 12
Percent Change From Baseline in Total Cholesterol at Week 12
Time Frame: Baseline and week 12
Baseline and week 12
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12
Time Frame: Baseline and weeks 10 and 12
Baseline and weeks 10 and 12
Percent Change From Baseline in Lipoprotein(a) at Week 12
Time Frame: Baseline and week 12
Baseline and week 12
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Time Frame: Baseline and weeks 10 and 12
Baseline and weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12
Time Frame: Baseline and week 12
Baseline and week 12
Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12
Time Frame: Baseline and weeks 10 and 12
Baseline and weeks 10 and 12
Percent Change From Baseline in HDL-C at Week 12
Time Frame: Baseline and week 12
Baseline and week 12
Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12
Time Frame: Baseline and weeks 10 and 12
Baseline and weeks 10 and 12
Percent Change From Baseline in VLDL-C at Week 12
Time Frame: Baseline and week 12
Baseline and week 12
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL
Time Frame: Weeks 10 and 12
Mean low density lipoprotein-cholesterol response was defined as LDL-C < 70 mg/dL [1.8 mol/L].
Weeks 10 and 12
Percentage of Participants Who Achieved a LDL-C of Less Than 70 mg/dL at Week 12
Time Frame: Week 12
Week 12
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12
Time Frame: Baseline and weeks 10 and 12
Baseline and weeks 10 and 12
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
Time Frame: Baseline and week 12
Baseline and week 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12
Time Frame: Baseline and weeks 10 and 12
Baseline and weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12
Time Frame: Baseline and week 12
Baseline and week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 27, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 10, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 26, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 16, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 18, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 10, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 20, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20140234

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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