Ezetimibe (EZ)/Atorvastatin (Ator) (MK-0653C) vs. Ator in Chinese Hypercholesterolemic Participants (MK-0653C-439)

A Phase 3 Randomized, Active-comparator-controlled Clinical Study to Evaluate the Efficacy and Safety of Ezetimibe/Atorvastatin Combination Tablet (MK-0653C) as Second Line Lipid Lowing Treatment in Chinese Participants

Sponsors

Lead Sponsor: Merck Sharp & Dohme Corp.

Source Merck Sharp & Dohme Corp.
Brief Summary

This study will evaluate the EZ/Ator fixed-dose combination (FDC) tablet (MK-0653C) as second line Low-Density Lipoprotein - Cholesterol (LDL-C) treatment in Chinese participants. The primary hypothesis is that MK-0653C 10/10 mg is superior to atorvastatin 20 mg in percent change from baseline in LDL-C to 12 weeks after treatment.

Overall Status Completed
Start Date 2019-05-27
Completion Date 2021-04-01
Primary Completion Date 2021-03-17
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Percent Change from Baseline in LDL-C at Week 12 (Cohort A) Baseline and Week 12
Percent Change from Baseline in LDL-C at Week 12 (Cohort B) Baseline and Week 12
Secondary Outcome
Measure Time Frame
Number of Participants with An Adverse Event (AE) Up to 14 weeks
Number of Participants Who Discontinued From Study Treatment Up to 12 weeks
Enrollment 454
Condition
Intervention

Intervention Type: Combination Product

Intervention Name: EZ 10 mg/Ator 10 mg

Description: FDC of EZ10 mg/Ator 10mg

Arm Group Label: EZ 10 mg/Ator 10 mg

Intervention Type: Combination Product

Intervention Name: EZ 10 mg/Ator 20 mg

Description: FDC of EZ10 mg/Ator 20mg

Arm Group Label: EZ 10 mg/Ator 20 mg

Intervention Type: Drug

Intervention Name: Atorvastatin

Description: Atorvastatin administered orally QD, either as two 10 mg tablets or as two 20 mg tablets

Other Name: Lipitor^®

Intervention Type: Drug

Intervention Name: Placebo for FDC EZ/Ator

Description: A single placebo tablet administered orally QD for 84 days

Intervention Type: Drug

Intervention Name: Placebo for atorvastatin

Description: Two placebo tablets matching atorvastatin administered orally QD for 84 days

Eligibility

Criteria:

Inclusion Criteria: - Has hypercholesterolemia diagnosed by investigator according to Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults (2016 Edition). - Has been stabilized on atorvastatin treatment at 10 mg or 20 mg (or other statins with LDL-C lowering efficacy equivalent to atorvastatin) for at least 4 weeks prior to Visit 1. - If female, is not pregnant or breastfeeding, and is either not a woman of childbearing potential (WOCBP), or is a WOCBP who has used a contraceptive consistent with local regulations. - If male, has used a contraceptive consistent with local regulations. - Agrees to maintain a stable diet and stable exercise during the study. Exclusion Criteria: - Has uncontrolled hypertriglyceridemia which needs drug intervention or a fasting triglyceride (TG) value ≥500 mg/dL (4.52 mmol/L). - Is currently treated with statin at dose of equivalent LDL-C lowering effect >20 mg atorvastatin. - Has active liver disease - Has New York Heart Association (NYHA) Class III or IV symptomatic congestive heart failure at Visit 1. - Has had uncontrolled cardiac arrhythmias, myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, unstable angina, or stroke within 3 months (12 weeks) prior to Visit 1. - Has homozygous familial hypercholesterolemia or has undergone LDL apheresis. - Has endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e., secondary causes of hyperlipidemia, e.g., hyper or hypothyroidism, Cushing's syndrome). - Has had a gastrointestinal tract bypass, or other significant intestinal malabsorption. - Has a history of cancer within the past 5 years from Visit 1 (except for successfully treated dermatological basal cell or squamous cell carcinoma or in situ cervical cancer). - Is known to be human immunodeficiency virus (HIV) positive. - Has hypersensitivity or intolerance to ezetimibe, atorvastatin, the ezetimibe/atorvastatin combination tablet, or any component of these medications or has a condition or situation, which is described as a contraindication in labeling of EZETROL or Lipitor or may interfere with participation in the study. - Has disorders of the hematologic, digestive, or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation. - Has a history of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy. - Has a history of myopathy or rhabdomyolysis with ezetimibe or any statin. - Is a WOCBP who has had a positive urine pregnancy test within 24 hours before the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. - Is currently taking medications that are potent modulators of cytochrome P-450 3A4 (CYP3A4) including: cyclosporine, systemically administered azole antifungals (e.g., ketoconazole, fluconazole, and itraconazole), macrolide antibiotics (e.g., clarithromycin, and erythromycin), protease inhibitors (e.g., ritonavir, saquinavir, and lopinavir), grapefruit or juice of grapefruit (200 ml/day for >3 times per week) - Is taking any cyclical hormones (e.g., cyclical oral contraceptives, cyclical hormone replacement), including the combination of ethinyl estradiol and norethisterone, or non-cyclical hormones, including non-cyclical hormone replacement therapy (HRT) or any estrogen antagonist/agonist within 8 weeks. - Note: If participant has been treated with a stable regimen of non-cyclical HRT for > 8 weeks and agree to continue this regimen for the duration of the trial, concomitant therapy is acceptable. - Is receiving treatment with systemic corticosteroids (intravenous, intramuscular and oral steroids). - Is treated with psyllium, other fiber-based laxatives, phytosterol margarine, and herbal medicine and/or over the counter (OTC) therapies that are known to affect serum lipids. - Note: If participant has been treated with a stable regimen for > 8 weeks and agrees to continue this regimen for the duration of the trial, concomitant therapy is acceptable. - Is treated with an anti-obesity drug (e.g. mazindol) within 12 weeks prior to Visit 1. - Is treated with warfarin or warfarin-like anticoagulants and has not been on a stable dose with a stable International Normalized Ratio (INR) for at least 6 weeks. weeks. - Has taken lipid-lowering agents (except probucol) including, Cholestin, bile acid sequestrants, ezetimibe, fibrates or niacin (>200 mg/day), proprotein convertases subtilisin/kexin type 9 (PCSK9) inhibitors within 6 weeks prior to Visit 1. - Has taken probucol within 10 weeks prior to Visit 1. - Has been treated with any other investigational drug within 30 days. - Currently follows an excessive weight reduction diet. - Currently engages in a vigorous exercise regimen (e.g., marathon training, body building training) or intends to start training during the study.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

80 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Medical Director Study Director Merck Sharp & Dohme Corp.
Location
Facility:
The First Affiliated Hospital of Baotou Medical College ( Site 0025) | Baotou, Anhui, 014010, China
Beijing Anzhen Hospital. Capital Medical University ( Site 0001) | Beijing, Anhui, 100024, China
Aero Space center hospital ( Site 0003) | Beijing, Beijing, 100049, China
Beijing Friendship Hospital ( Site 0005) | Beijing, Beijing, 100050, China
Chongqing General Hospital ( Site 0037) | Chongqing, Chongqing, 400013, China
Lanzhou University Second Hospital ( Site 0041) | Lanzhou, Gansu, 730030, China
Guangdong General Hospital ( Site 0006) | Guangzhou, Guangdong, 510080, China
The First Affiliated Hospital.Sun Yat-sen University ( Site 0007) | Guangzhou, Guangdong, 510080, China
Sun Yat-sen Memorial Hospital of Sun Yat-sen University ( Site 0008) | Guangzhou, Guangdong, 510210, China
Daqing Oilfield General Hospital ( Site 0010) | Daqing, Heilongjiang, 163001, China
The first affiliated Hospital of Harbin Medical University ( Site 0009) | Haerbin, Heilongjiang, 150001, China
The Third Xiangya Hospital of Central South University ( Site 0013) | Changsha, Hunan, 410000, China
Hunan Provincial People's Hospital ( Site 0011) | Changsha, Hunan, 410005, China
Zhongda Hospital Southeast University ( Site 0045) | Nanjing, Jiangsu, 210009, China
The Second Affiliated Hospital of Nanjing Medical University ( Site 0020) | Nanjing, Jiangsu, 210011, China
First Affiliated Hospital of Soochow University ( Site 0048) | Suzhou, Jiangsu, 215006, China
The Affiliated Hospital of Xuzhou Medical University ( Site 0017) | Xuzhou, Jiangsu, 221000, China
Subei People's Hospital ( Site 0040) | Yangzhou, Jiangsu, 225001, China
Second Affiliated Hospital of Nanchang University ( Site 0038) | Nanchang, Jiangxi, 330006, China
Ji Lin Province People Hospital ( Site 0016) | Changchun, Jilin, 130021, China
China-Japan Union Hospital of Jilin University ( Site 0015) | Changchun, Jilin, 130033, China
Central People s Hospital of Siping ( Site 0046) | Siping, Jilin, 136000, China
The People's Hospital of Liaoning Province-Cardiovascular ( Site 0022) | Shenyang, Liaoning, 110016, China
Zhongshan Hospital Fudan University ( Site 0049) | Shanghai, Shanghai, 200032, China
Shanghai Tongji Hospital ( Site 0031) | Shanghai, Shanghai, 200065, China
Tianjin Union Medicine Centre ( Site 0032) | Tianjin, Tianjin, 300121, China
People s Hospital of Lishui City ( Site 0036) | Lishui, Zhejiang, 323000, China
Ningbo First Hospital ( Site 0042) | Ningbo, Zhejiang, 315010, China
Taizhou Hospital of Zhejiang Province ( Site 0035) | Taizhou, Zhejiang, 317000, China
The First Affiliated Hospital of Wenzhou Medical University ( Site 0034) | Wenzhou, Zhejiang, 325000, China
Location Countries

China

Verification Date

2021-04-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: EZ 10 mg/Ator 10 mg

Type: Experimental

Description: Single oral dose of EZ10mg/Ator10mg FDC tablet once daily (QD) for 84 days

Label: Atorvastatin 20 mg

Type: Active Comparator

Description: 2 atorvastatin 10 mg tablets administered orally, QD for 84 days

Label: EZ 10 mg/Ator 20 mg

Type: Experimental

Description: Single oral dose of EZ10mg/Ator20mg FDC tablet QD for 84 days

Label: Atorvastatin 40 mg

Type: Active Comparator

Description: 2 atorvastatin 20 mg tablets administered orally, QD for 84 days

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

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