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

Hypercholesterolemia Clinical Trial

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 Lowering Treatment in Chinese Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03768427
• Other study ID #: 0653C-439
• Secondary ID: MK-0653C-439
• Status: Completed
• Phase: Phase 3
• Start date: May 27, 2019
• Est. completion date: April 1, 2021

Study information

• Verified date: April 2023
• Source: Organon and Co
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 454
• Est. completion date: April 1, 2021
• Est. primary completion date: March 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Combination Product:
• EZ 10 mg/Ator 10 mg
FDC of EZ10 mg/Ator 10mg
• EZ 10 mg/Ator 20 mg
FDC of EZ10 mg/Ator 20mg

Drug:
• Atorvastatin
Atorvastatin administered orally QD, either as two 10 mg tablets or as two 20 mg tablets
• Placebo for FDC EZ/Ator
A single placebo tablet administered orally QD for 84 days
• Placebo for atorvastatin
Two placebo tablets matching atorvastatin administered orally QD for 84 days

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Baotou Medical College ( Site 0025)	Baotou	Anhui
China	Aero Space center hospital ( Site 0003)	Beijing	Beijing
China	Beijing Anzhen Hospital. Capital Medical University ( Site 0001)	Beijing	Anhui
China	Beijing Friendship Hospital ( Site 0005)	Beijing	Beijing
China	China-Japan Union Hospital of Jilin University ( Site 0015)	Changchun	Jilin
China	Ji Lin Province People Hospital ( Site 0016)	Changchun	Jilin
China	Hunan Provincial People's Hospital ( Site 0011)	Changsha	Hunan
China	The Third Xiangya Hospital of Central South University ( Site 0013)	Changsha	Hunan
China	Chongqing General Hospital ( Site 0037)	Chongqing	Chongqing
China	Daqing Oilfield General Hospital ( Site 0010)	Daqing	Heilongjiang
China	Guangdong General Hospital ( Site 0006)	Guangzhou	Guangdong
China	Sun Yat-sen Memorial Hospital of Sun Yat-sen University ( Site 0008)	Guangzhou	Guangdong
China	The First Affiliated Hospital.Sun Yat-sen University ( Site 0007)	Guangzhou	Guangdong
China	The first affiliated Hospital of Harbin Medical University ( Site 0009)	Haerbin	Heilongjiang
China	Lanzhou University Second Hospital ( Site 0041)	Lanzhou	Gansu
China	People s Hospital of Lishui City ( Site 0036)	Lishui	Zhejiang
China	Second Affiliated Hospital of Nanchang University ( Site 0038)	Nanchang	Jiangxi
China	The Second Affiliated Hospital of Nanjing Medical University ( Site 0020)	Nanjing	Jiangsu
China	Zhongda Hospital Southeast University ( Site 0045)	Nanjing	Jiangsu
China	Ningbo First Hospital ( Site 0042)	Ningbo	Zhejiang
China	Shanghai Tongji Hospital ( Site 0031)	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University ( Site 0049)	Shanghai	Shanghai
China	The People's Hospital of Liaoning Province-Cardiovascular ( Site 0022)	Shenyang	Liaoning
China	Central People s Hospital of Siping ( Site 0046)	Siping	Jilin
China	First Affiliated Hospital of Soochow University ( Site 0048)	Suzhou	Jiangsu
China	Taizhou Hospital of Zhejiang Province ( Site 0035)	Taizhou	Zhejiang
China	Tianjin Union Medicine Centre ( Site 0032)	Tianjin	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University ( Site 0034)	Wenzhou	Zhejiang
China	The Affiliated Hospital of Xuzhou Medical University ( Site 0017)	Xuzhou	Jiangsu
China	Subei People's Hospital ( Site 0040)	Yangzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Organon and Co

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in LDL-C at Week 12	Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration. The change from baseline was calculated.	Baseline (Day 1) and Week 12
Secondary	Percentage of Participants With An Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 17 weeks
Secondary	Number of Participants Who Discontinued From Study Treatment	The number of participants who discontinued treatment over the 12-week treatment period was assessed.	Up to approximately 15 weeks