Ezetimibe (EZ)/Atorvastatin (Ator) (MK-0653C) vs. Ator in Chinese Hypercholesterolemic Participants (MK-0653C-439)
Condition: Hypercholesterolemia
MeSH terms: Hypercholesterolemia
Intervention: EZ 10 mg/Ator 10 mg; EZ 10 mg/Ator 20 mg; Atorvastatin; Placebo for FDC EZ/Ator; Placebo for atorvastatin
Intervention description: FDC of EZ10 mg/Ator 10mg; FDC of EZ10 mg/Ator 20mg; Atorvastatin administered orally QD, either as two 10 mg tablets or as two 20 mg tablets; A single placebo tablet administered orally QD for 84 days; Two placebo tablets matching atorvastatin administered orally QD for 84 days
Intervention MeSH terms: Atorvastatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 454.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

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.