Clinical trial NCT03768427: Ezetimibe (EZ)/Atorvastatin (Ator) (MK-0653C) vs. Ator in Chinese Hypercholesterolemic Participants (MK-0653C-439)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2018-12-07
Enrollment: 454
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percent Change From Baseline in LDL-C at Week 12
timeFrame: Baseline (Day 1) and Week 12
Secondary outcomes:
measure: Percentage of Participants With An Adverse Event (AE)
timeFrame: Up to approximately 17 weeks
measure: Number of Participants Who Discontinued From Study Treatment
timeFrame: Up to approximately 15 weeks
Other outcomes:
Locations:
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College ( Site 0025)
state: Anhui
city: Beijing
country: China
facility: Beijing Anzhen Hospital. Capital Medical University ( Site 0001)
state: Anhui
city: Beijing
country: China
facility: Aero Space center hospital ( Site 0003)
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital ( Site 0005)
state: Beijing
city: Chongqing
country: China
facility: Chongqing General Hospital ( Site 0037)
state: Chongqing
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital ( Site 0041)
state: Gansu
city: Guangzhou
country: China
facility: Guangdong General Hospital ( Site 0006)
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital.Sun Yat-sen University ( Site 0007)
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital of Sun Yat-sen University ( Site 0008)
state: Guangdong
city: Daqing
country: China
facility: Daqing Oilfield General Hospital ( Site 0010)
state: Heilongjiang
city: Haerbin
country: China
facility: The first affiliated Hospital of Harbin Medical University ( Site 0009)
state: Heilongjiang
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University ( Site 0013)
state: Hunan
city: Changsha
country: China
facility: Hunan Provincial People's Hospital ( Site 0011)
state: Hunan
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University ( Site 0045)
state: Jiangsu
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University ( Site 0020)
state: Jiangsu
city: Suzhou
country: China
facility: First Affiliated Hospital of Soochow University ( Site 0048)
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University ( Site 0017)
state: Jiangsu
city: Yangzhou
country: China
facility: Subei People's Hospital ( Site 0040)
state: Jiangsu
city: Nanchang
country: China
facility: Second Affiliated Hospital of Nanchang University ( Site 0038)
state: Jiangxi
city: Changchun
country: China
facility: Ji Lin Province People Hospital ( Site 0016)
state: Jilin
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University ( Site 0015)
state: Jilin
city: Siping
country: China
facility: Central People s Hospital of Siping ( Site 0046)
state: Jilin
city: Shenyang
country: China
facility: The People's Hospital of Liaoning Province-Cardiovascular ( Site 0022)
state: Liaoning
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University ( Site 0049)
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tongji Hospital ( Site 0031)
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Union Medicine Centre ( Site 0032)
state: Tianjin
city: Lishui
country: China
facility: People s Hospital of Lishui City ( Site 0036)
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo First Hospital ( Site 0042)
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province ( Site 0035)
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University ( Site 0034)
state: Zhejiang
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.