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

Organon

Status and phase: Completed; Phase 3

Conditions: Hypercholesterolemia

Treatments: Combination Product: EZ 10 mg/Ator 10 mg; Combination Product: EZ 10 mg/Ator 20 mg; Drug: Placebo for FDC EZ/Ator; Drug: Atorvastatin; Drug: Placebo for atorvastatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03768427

0653C-439

MK-0653C-439 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 454 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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454 participants in 4 patient groups

EZ 10 mg/Ator 10 mg

Experimental group

Description:

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

Treatment:

Combination Product: EZ 10 mg/Ator 10 mg

Drug: Placebo for FDC EZ/Ator

Atorvastatin 20 mg

Active Comparator group

Description:

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

Treatment:

Drug: Atorvastatin

Drug: Placebo for atorvastatin

EZ 10 mg/Ator 20 mg

Experimental group

Description:

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

Treatment:

Drug: Placebo for FDC EZ/Ator

Combination Product: EZ 10 mg/Ator 20 mg

Atorvastatin 40 mg

Active Comparator group

Description:

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

Treatment:

Drug: Atorvastatin

Drug: Placebo for atorvastatin