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

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ClinicalTrials.gov Identifier: NCT03768427
Recruitment Status : Recruiting
First Posted : December 7, 2018
Last Update Posted : September 2, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Combination Product: EZ 10 mg/Ator 10 mg Combination Product: EZ 10 mg/Ator 20 mg Drug: Atorvastatin Drug: Placebo for FDC EZ/Ator Drug: Placebo for atorvastatin Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 27, 2019
Estimated Primary Completion Date : January 1, 2021
Estimated Study Completion Date : February 26, 2021


Arm Intervention/treatment
Experimental: EZ 10 mg/Ator 10 mg
Single oral dose of EZ10mg/Ator10mg FDC tablet once daily (QD) for 84 days
Combination Product: EZ 10 mg/Ator 10 mg
FDC of EZ10 mg/Ator 10mg

Drug: Placebo for FDC EZ/Ator
A single placebo tablet administered orally QD for 84 days

Active Comparator: Atorvastatin 20 mg
2 atorvastatin 10 mg tablets administered orally, QD for 84 days
Drug: Atorvastatin
Atorvastatin administered orally QD, either as two 10 mg tablets or as two 20 mg tablets
Other Name: Lipitor^®

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

Experimental: EZ 10 mg/Ator 20 mg
Single oral dose of EZ10mg/Ator20mg FDC tablet QD for 84 days
Combination Product: EZ 10 mg/Ator 20 mg
FDC of EZ10 mg/Ator 20mg

Drug: Placebo for FDC EZ/Ator
A single placebo tablet administered orally QD for 84 days

Active Comparator: Atorvastatin 40 mg
2 atorvastatin 20 mg tablets administered orally, QD for 84 days
Drug: Atorvastatin
Atorvastatin administered orally QD, either as two 10 mg tablets or as two 20 mg tablets
Other Name: Lipitor^®

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




Primary Outcome Measures :
  1. Percent Change from Baseline in LDL-C at Week 12 (Cohort A) [ Time Frame: Baseline and Week 12 ]
    Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration. The change from baseline was calculated.

  2. Percent Change from Baseline in LDL-C at Week 12 (Cohort B) [ Time Frame: Baseline and Week 12 ]
    Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration. The change from baseline was calculated.


Secondary Outcome Measures :
  1. Number of Participants with An Adverse Event (AE) [ Time Frame: Up to 14 weeks ]
    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. The number of participants in any treatment group with at least one AE was assessed over 12 weeks of treatment with MK-0653C, plus 14 days (2 weeks) of follow-up.

  2. Number of Participants Who Discontinued From Study Treatment [ Time Frame: Up to 12 weeks ]
    The number of participants who discontinued treatment over the 12-week treatment period was assessed.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT03768427


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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China, Beijing
Aero Space center hospital ( Site 0003) Recruiting
Beijing, Beijing, China, 100049
Contact: Study Coordinator    +861059971771      
China, Chongqing
Chongqing General Hospital ( Site 0037) Recruiting
Chongqing, Chongqing, China, 400013
Contact: Study Coordinator    +8613508322668      
China, Gansu
Lanzhou University Second Hospital ( Site 0041) Recruiting
Lanzhou, Gansu, China, 730030
Contact: Study Coordinator    +869318942924      
China, Heilongjiang
Daqing Oilfield General Hospital ( Site 0010) Recruiting
Daqing, Heilongjiang, China, 163001
Contact: Study Coordinator    +864595805301      
China, Hunan
Hunan Provincial People's Hospital ( Site 0011) Recruiting
Changsha, Hunan, China, 410005
Contact: Study Coordinator    +8613974829586      
China, Inner Mongolia
The First Affiliated Hospital of Baotou Medical College ( Site 0025) Recruiting
Baotou, Inner Mongolia, China, 014010
Contact: Study Coordinator    +864722178224      
China, Jiangsu
The Affiliated Hospital of Xuzhou Medical University ( Site 0017) Recruiting
Xuzhou, Jiangsu, China, 221000
Contact: Study Coordinator    +8613805219897      
Subei People's Hospital ( Site 0040) Recruiting
Yangzhou, Jiangsu, China, 225001
Contact: Study Coordinator    +8618952781166      
China, Jiangxi
Second Affiliated Hospital of Nanchang University ( Site 0038) Recruiting
Nanchang, Jiangxi, China, 330006
Contact: Study Coordinator    +86079186312723      
China, Jilin
Ji Lin Province People Hospital,Urology ( Site 0016) Recruiting
Changchun, Jilin, China, 130021
Contact: Study Coordinator    +86043185595585      
China-Japan Union Hospital of Jilin University ( Site 0015) Recruiting
Changchun, Jilin, China, 130033
Contact: Study Coordinator    +86043184995395      
Central People s Hospital of Siping ( Site 0046) Recruiting
Siping, Jilin, China, 136000
Contact: Study Coordinator    +8604343625127      
China, Liaoning
The People's Hospital of Liaoning Province-Cardiovascular ( Site 0022) Recruiting
Shenyang, Liaoning, China, 110016
Contact: Study Coordinator    +8613904027391      
China, Shanghai
Zhongshan Hospital Fudan University ( Site 0049) Recruiting
Shanghai, Shanghai, China, 200032
Contact: Study Coordinator    +862160267665      
Shanghai Tongji Hospital ( Site 0031) Recruiting
Shanghai, Shanghai, China, 200065
Contact: Study Coordinator    +8602166111103      
China, Zhejiang
People's Hospital of Lishui City ( Site 0036) Recruiting
Lishui, Zhejiang, China, 323000
Contact: Study Coordinator    +8605782780123      
Ningbo First Hospital ( Site 0042) Recruiting
Ningbo, Zhejiang, China, 315010
Contact: Study Coordinator    +8602166111103      
Taizhou Hospital of Zhejiang Province ( Site 0035) Recruiting
Taizhou, Zhejiang, China, 317000
Contact: Study Coordinator    +86057685199091      
China
Beijing Anzhen Hospital. Capital Medical University ( Site 0001) Recruiting
Beijing, China, 100024
Contact: Study Coordinator    +8613651327758      
Beijing Friendship Hospital ( Site 0005) Recruiting
Beijing, China, 100050
Contact: Study Coordinator    +861063138628      
Tianjin Union Medicine Centre ( Site 0032) Recruiting
Tianjin, China, 300121
Contact: Study Coordinator    +862258987310      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03768427     History of Changes
Other Study ID Numbers: 0653C-439
MK-0653C-439 ( Other Identifier: Merck Protocol Number )
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: September 2, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin
Ezetimibe
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors