Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    20140234
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02634580
Recruitment Status : Completed
First Posted : December 18, 2015
Results First Posted : August 31, 2018
Last Update Posted : August 31, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

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.

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Biological: Evolocumab Drug: Ezetimibe Drug: Placebo to Evolocumab Drug: Placebo Ezetimibe Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : February 27, 2016
Actual Primary Completion Date : August 10, 2017
Actual Study Completion Date : May 26, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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:
  • AMG 145
  • Repatha

Drug: Ezetimibe
Tablet for oral administration
Other Name: 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:
  • AMG 145
  • Repatha

Drug: Ezetimibe
Tablet for oral administration
Other Name: 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:
  • AMG 145
  • Repatha

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:
  • AMG 145
  • Repatha

Drug: Placebo Ezetimibe
Tablet for oral administration




Primary Outcome Measures :
  1. 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.

  2. Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline and week 12 ]

Secondary Outcome Measures :
  1. Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and weeks 10 and 12 ]
  2. Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and week 12 ]
  3. 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].

  4. Percentage of Participants Who Achieved a LDL-C of Less Than 70 mg/dL at Week 12 [ Time Frame: Week 12 ]
  5. Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and weeks 10 and 12 ]
  6. Percent Change From Baseline in Total Cholesterol at Week 12 [ Time Frame: Baseline and week 12 ]
  7. Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and weeks 10 and 12 ]
  8. Percent Change From Baseline in Non-HDL-C at Week 12 [ Time Frame: Baseline and week 12 ]
  9. Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
  10. Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and week 12 ]
  11. 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 ]
  12. Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 [ Time Frame: Baseline and week 12 ]
  13. 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 ]
  14. Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 [ Time Frame: Baseline and week 12 ]
  15. Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and weeks 10 and 12 ]
  16. Percent Change From Baseline in Lipoprotein(a) at Week 12 [ Time Frame: Baseline and week 12 ]
  17. Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and weeks 10 and 12 ]
  18. Percent Change From Baseline in Triglycerides at Week 12 [ Time Frame: Baseline and week 12 ]
  19. Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and weeks 10 and 12 ]
  20. Percent Change From Baseline in HDL-C at Week 12 [ Time Frame: Baseline and week 12 ]
  21. Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and weeks 10 and 12 ]
  22. Percent Change From Baseline in VLDL-C at Week 12 [ Time Frame: Baseline and week 12 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02634580


Locations
Layout table for location information
Japan
Research Site
Nagoya-shi, Aichi, Japan, 466-8560
Research Site
Nagoya-shi, Aichi, Japan, 466-8650
Research Site
Chiba-shi, Chiba, Japan, 260-8677
Research Site
Kisarazu-shi, Chiba, Japan, 292-8535
Research Site
Matsudo-shi, Chiba, Japan, 271-0077
Research Site
Chikushino-shi, Fukuoka, Japan, 818-8516
Research Site
Koga-shi, Fukuoka, Japan, 811-3195
Research Site
Sukagawa-shi, Fukushima, Japan, 962-0001
Research Site
Sukagawa-shi, Fukushima, Japan, 962-8503
Research Site
Hiroshima-shi, Hiroshima, Japan, 734-8551
Research Site
Kobe-shi, Hyogo, Japan, 650-0017
Research Site
Koga-shi, Ibaraki, Japan, 306-0041
Research Site
Kahoku-gun, Ishikawa, Japan, 920-0293
Research Site
Kanazawa-shi, Ishikawa, Japan, 920-8650
Research Site
Komatsu-shi, Ishikawa, Japan, 923-8560
Research Site
Morioka-shi, Iwate, Japan, 020-0866
Research Site
Morioka-shi, Iwate, Japan, 020-8505
Research Site
Kagoshima-shi, Kagoshima, Japan, 890-8520
Research Site
Yokohama-shi, Kanagawa, Japan, 245-8575
Research Site
Kumamoto-shi, Kumamoto, Japan, 860-8556
Research Site
Kumamoto-shi, Kumamoto, Japan, 862-0976
Research Site
Kyoto-shi, Kyoto, Japan, 606-8507
Research Site
Ohsaki-shi, Miyagi, Japan, 989-6143
Research Site
Nakagami-gun, Okinawa, Japan, 901-2393
Research Site
Osaka-shi, Osaka, Japan, 530-0001
Research Site
Osaka-Shi, Osaka, Japan, 553-0003
Research Site
Fujimi-shi, Saitama, Japan, 354-0031
Research Site
Iruma-gun, Saitama, Japan, 350-0495
Research Site
Kawaguchi-shi, Saitama, Japan, 332-0012
Research Site
Hamamatsu-shi, Shizuoka, Japan, 430-0929
Research Site
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
Sponsors and Collaborators
Amgen
Investigators
Layout table for investigator information
Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] March 21, 2017
Statistical Analysis Plan  [PDF] May 16, 2018


Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02634580    
Other Study ID Numbers: 20140234
First Posted: December 18, 2015    Key Record Dates
Results First Posted: August 31, 2018
Last Update Posted: August 31, 2018
Last Verified: August 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Japanese
High cholesterol
Treatment of high cholesterol
Lowering cholesterol
Lowering high cholesterol
Hypercholesterolemia
Statin intolerant
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Ezetimibe
Evolocumab
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Immunologic Factors
Physiological Effects of Drugs