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

NCT ID: NCT03768427

Last Updated: 2024-05-16

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

454 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-27

Study Completion Date

2021-04-01

Brief Summary

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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.

Detailed Description

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Conditions

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Hypercholesterolemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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EZ 10 mg/Ator 10 mg

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

Group Type EXPERIMENTAL

EZ 10 mg/Ator 10 mg

Intervention Type COMBINATION_PRODUCT

FDC of EZ10 mg/Ator 10mg

Placebo for FDC EZ/Ator

Intervention Type DRUG

A single placebo tablet administered orally QD for 84 days

Atorvastatin 20 mg

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

Group Type ACTIVE_COMPARATOR

Atorvastatin

Intervention Type DRUG

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

Placebo for atorvastatin

Intervention Type DRUG

Two placebo tablets matching atorvastatin administered orally QD for 84 days

EZ 10 mg/Ator 20 mg

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

Group Type EXPERIMENTAL

EZ 10 mg/Ator 20 mg

Intervention Type COMBINATION_PRODUCT

FDC of EZ10 mg/Ator 20mg

Placebo for FDC EZ/Ator

Intervention Type DRUG

A single placebo tablet administered orally QD for 84 days

Atorvastatin 40 mg

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

Group Type ACTIVE_COMPARATOR

Atorvastatin

Intervention Type DRUG

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

Placebo for atorvastatin

Intervention Type DRUG

Two placebo tablets matching atorvastatin administered orally QD for 84 days

Interventions

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EZ 10 mg/Ator 10 mg

FDC of EZ10 mg/Ator 10mg

Intervention Type COMBINATION_PRODUCT

EZ 10 mg/Ator 20 mg

FDC of EZ10 mg/Ator 20mg

Intervention Type COMBINATION_PRODUCT

Atorvastatin

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

Intervention Type DRUG

Placebo for FDC EZ/Ator

A single placebo tablet administered orally QD for 84 days

Intervention Type DRUG

Placebo for atorvastatin

Two placebo tablets matching atorvastatin administered orally QD for 84 days

Intervention Type DRUG

Other Intervention Names

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Lipitor^®

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Organon and Co

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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The First Affiliated Hospital of Baotou Medical College ( Site 0025)

Baotou, Anhui, China

Site Status

Beijing Anzhen Hospital. Capital Medical University ( Site 0001)

Beijing, Anhui, China

Site Status

Aero Space center hospital ( Site 0003)

Beijing, Beijing Municipality, China

Site Status

Beijing Friendship Hospital ( Site 0005)

Beijing, Beijing Municipality, China

Site Status

Chongqing General Hospital ( Site 0037)

Chongqing, Chongqing Municipality, China

Site Status

Lanzhou University Second Hospital ( Site 0041)

Lanzhou, Gansu, China

Site Status

Guangdong General Hospital ( Site 0006)

Guangzhou, Guangdong, China

Site Status

The First Affiliated Hospital.Sun Yat-sen University ( Site 0007)

Guangzhou, Guangdong, China

Site Status

Sun Yat-sen Memorial Hospital of Sun Yat-sen University ( Site 0008)

Guangzhou, Guangdong, China

Site Status

Daqing Oilfield General Hospital ( Site 0010)

Daqing, Heilongjiang, China

Site Status

The first affiliated Hospital of Harbin Medical University ( Site 0009)

Haerbin, Heilongjiang, China

Site Status

The Third Xiangya Hospital of Central South University ( Site 0013)

Changsha, Hunan, China

Site Status

Hunan Provincial People's Hospital ( Site 0011)

Changsha, Hunan, China

Site Status

Zhongda Hospital Southeast University ( Site 0045)

Nanjing, Jiangsu, China

Site Status

The Second Affiliated Hospital of Nanjing Medical University ( Site 0020)

Nanjing, Jiangsu, China

Site Status

First Affiliated Hospital of Soochow University ( Site 0048)

Suzhou, Jiangsu, China

Site Status

The Affiliated Hospital of Xuzhou Medical University ( Site 0017)

Xuzhou, Jiangsu, China

Site Status

Subei People's Hospital ( Site 0040)

Yangzhou, Jiangsu, China

Site Status

Second Affiliated Hospital of Nanchang University ( Site 0038)

Nanchang, Jiangxi, China

Site Status

Ji Lin Province People Hospital ( Site 0016)

Changchun, Jilin, China

Site Status

China-Japan Union Hospital of Jilin University ( Site 0015)

Changchun, Jilin, China

Site Status

Central People s Hospital of Siping ( Site 0046)

Siping, Jilin, China

Site Status

The People's Hospital of Liaoning Province-Cardiovascular ( Site 0022)

Shenyang, Liaoning, China

Site Status

Zhongshan Hospital Fudan University ( Site 0049)

Shanghai, Shanghai Municipality, China

Site Status

Shanghai Tongji Hospital ( Site 0031)

Shanghai, Shanghai Municipality, China

Site Status

Tianjin Union Medicine Centre ( Site 0032)

Tianjin, Tianjin Municipality, China

Site Status

People s Hospital of Lishui City ( Site 0036)

Lishui, Zhejiang, China

Site Status

Ningbo First Hospital ( Site 0042)

Ningbo, Zhejiang, China

Site Status

Taizhou Hospital of Zhejiang Province ( Site 0035)

Taizhou, Zhejiang, China

Site Status

The First Affiliated Hospital of Wenzhou Medical University ( Site 0034)

Wenzhou, Zhejiang, China

Site Status

Countries

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China

References

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Qian J, Li Z, Zhang X, Chen J, Ding C, Yang P, Liu Y, Shi M, Ren X, Ge J; Phase III Study Investigators. Efficacy and Tolerability of Ezetimibe/Atorvastatin Fixed-dose Combination Versus Atorvastatin Monotherapy in Hypercholesterolemia: A Phase III, Randomized, Active-controlled Study in Chinese Patients. Clin Ther. 2022 Oct;44(10):1282-1296. doi: 10.1016/j.clinthera.2022.08.013. Epub 2022 Sep 29.

Reference Type DERIVED
PMID: 36182594 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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MK-0653C-439

Identifier Type: OTHER

Identifier Source: secondary_id

0653C-439

Identifier Type: -

Identifier Source: org_study_id

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