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

NCT02634580 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 20140234
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 35

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.

Conditions

Hypercholesterolemia

Keywords

Japanese; High cholesterol; Treatment of high cholesterol; Lowering cholesterol; Lowering high cholesterol; Hypercholesterolemia; Statin intolerant

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of 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

  Baseline and week 12

Secondary Outcomes (22)

• Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

  Baseline and weeks 10 and 12

• Change From Baseline in LDL-C at 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

  Weeks 10 and 12

• Percentage of Participants Who Achieved a LDL-C of Less Than 70 mg/dL at Week 12

  Week 12

• Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12

  Baseline and weeks 10 and 12

Study Arms (4)

Ezetimibe (Q2W)

ACTIVE COMPARATOR

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; Drug: Ezetimibe; Drug: Placebo to Evolocumab

Ezetimibe (QM)

ACTIVE COMPARATOR

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; Drug: Ezetimibe; Drug: Placebo to Evolocumab

Evolocumab Q2W

EXPERIMENTAL

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; Drug: Placebo Ezetimibe

Evolocumab QM

EXPERIMENTAL

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; Drug: Placebo Ezetimibe

Interventions

Evolocumab BIOLOGICAL

Administered by subcutaneous injection

Also known as: AMG 145, Repatha

Evolocumab Q2W; Evolocumab QM; Ezetimibe (Q2W); Ezetimibe (QM)

Ezetimibe DRUG

Tablet for oral administration

Also known as: Zetia

Ezetimibe (Q2W); Ezetimibe (QM)

Placebo to Evolocumab DRUG

Administered by subcutaneous injection

Ezetimibe (Q2W); Ezetimibe (QM)

Placebo Ezetimibe DRUG

Tablet for oral administration

Evolocumab Q2W; Evolocumab QM

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (35)

Research Site

Nagoya, Aichi-ken, 466-8560, Japan

Location

Research Site

Nagoya, Aichi-ken, 466-8650, Japan

Location

Research Site

Chiba, Chiba, 260-8677, Japan

Location

Research Site

Kisarazu-shi, Chiba, 292-8535, Japan

Location

Research Site

Matsudo-shi, Chiba, 271-0077, Japan

Location

Research Site

Chikushino-shi, Fukuoka, 818-8516, Japan

Location

Research Site

Koga-shi, Fukuoka, 811-3195, Japan

Location

Research Site

Sukagawa-shi, Fukushima, 962-0001, Japan

Location

Research Site

Sukagawa-shi, Fukushima, 962-8503, Japan

Location

Research Site

Hiroshima, Hiroshima, 734-8551, Japan

Location

Research Site

Kobe, Hyōgo, 650-0017, Japan

Location

Research Site

Koga-shi, Ibaraki, 306-0041, Japan

Location

Research Site

Kahoku-gun, Ishikawa-ken, 920-0293, Japan

Location

Research Site

Kanazawa, Ishikawa-ken, 920-8650, Japan

Location

Research Site

Komatsu-shi, Ishikawa-ken, 923-8560, Japan

Location

Research Site

Morioka, Iwate, 020-0866, Japan

Location

Research Site

Morioka, Iwate, 020-8505, Japan

Location

Research Site

Kagoshima, Kagoshima-ken, 890-8520, Japan

Location

Research Site

Yokohama, Kanagawa, 245-8575, Japan

Location

Research Site

Kumamoto, Kumamoto, 860-8556, Japan

Location

Research Site

Kumamoto, Kumamoto, 862-0976, Japan

Location

Research Site

Kyoto, Kyoto, 606-8507, Japan

Location

Research Site

Ohsaki-shi, Miyagi, 989-6143, Japan

Location

Research Site

Nakagami-gun, Okinawa, 901-2393, Japan

Location

Research Site

Osaka, Osaka, 530-0001, Japan

Location

Research Site

Osaka, Osaka, 553-0003, Japan

Location

Research Site

Fujimi-shi, Saitama, 354-0031, Japan

Location

Research Site

Iruma-gun, Saitama, 350-0495, Japan

Location

Research Site

Kawaguchi-shi, Saitama, 332-0012, Japan

Location

Research Site

Hamamatsu, Shizuoka, 430-0929, Japan

Location

Research Site

Bunkyo-ku, Tokyo, 113-8655, Japan

Location

Research Site

Chuo-ku, Tokyo, 103-0027, Japan

Location

Research Site

Higashiyamato-shi, Tokyo, 207-0014, Japan

Location

Research Site

Musashino-shi, Tokyo, 180-0022, Japan

Location

Research Site

Shinagawa-ku, Tokyo, 142-8666, Japan

Location

Related Publications (1)

• Koba S, Inoue I, Cyrille M, Lu C, Inomata H, Shimauchi J, Kajinami K. Evolocumab vs. Ezetimibe in Statin-Intolerant Hyperlipidemic Japanese Patients: Phase 3 GAUSS-4 Trial. J Atheroscler Thromb. 2020 May 1;27(5):471-484. doi: 10.5551/jat.50963. Epub 2019 Nov 21.

  PMID: 31748467 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

evolocumab; Ezetimibe

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: December 18, 2015
• Study Start: February 27, 2016
• Primary Completion: August 10, 2017
• Study Completion: May 26, 2018
• Last Updated: November 10, 2020
• Results First Posted: August 31, 2018

Record last verified: 2020-10

Locations

JP (35)