Clinical trial NCT02550288: A Clinical Trial to Assess the Efficacy and Safety of MK-0653C in Japanese Participants With Hypercholesterolemia (MK-0653C-383)
Official title: A Phase III, Randomized, Active Comparator-controlled Clinical Trial to Study the Efficacy and Safety of MK-0653C in Japanese Patients With Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2015-09-15
Enrollment: 309
Sex: ALL
Minimum age (years): 20
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 efficacy and safety of MK-0653C (Ezetimibe \[EZ\] 10 mg/Atorvastatin \[Atora\] 10mg or 20 mg) compared to EZ 10 mg, Atora 10 mg, or Atora 20 mg alone when administered to Japanese participants with hypercholesterolemia. The primary hypothesis is that MK-0653C (EZ 10 mg/Atorva 10 mg) is superior to EZ 10 mg and is superior to Atorva 10 mg and that MK-0653C (EZ 10 mg/Atorva 20 mg) is superior to EZ 10 mg and is superior to Atorva 20 mg in percent change from baseline in low-density lipoprotein cholesterol (LDL-C) after 12 weeks of treatment.


Eligibility criteria: Inclusion Criteria:

* Japanese outpatient with hypercholesterolemia.
* Females must be non-reproductive potential or agree to remain abstinent or use (or partner use) two acceptable methods of birth control from date of signed informed consent to the 14 days after the last dose of study drug
* Agree to maintain a stable diet that is consistent with the Japan Atherosclerosis Society Guideline 2012 (JAS2012) for prevention of atherosclerotic cardiovascular diseases for the duration of the study

Exclusion Criteria:

* Uncontrolled hypertension
* Type 1 or uncontrolled type 2 diabetes mellitus (treated or untreated)
* History of coronary artery disease (CAD) Homozygous familial hypercholesterolemia or has undergone LDL apheresis
* Had a gastrointestinal tract bypass, or other significant intestinal malabsorption
* History of cancer within the past 5 years except for successfully treated dermatological basal cell or squamous cell carcinoma or in situ cervical cancer
* Human immunodeficiency virus (HIV) positive
* History of drug/ alcohol abuse within the past 5 years or psychiatric illness not adequately controlled and stable on pharmacotherapy
* Consumes more than 25 g of alcohol per day
* Consumes more than 1L of grapefruit juice per day
* Currently following an excessive weight reduction diet
* Engaging in a vigorous exercise regimen (e.g.; marathon training, body building training etc.) or intends to start training during the study
* Hypersensitivity or intolerance to ezetimibe or atorvastatin
* History of myopathy or rhabdomyolysis with ezetimibe or any statin
* Pregnant or lactating
* Taking any other investigational drugs and/or has taken any investigational drugs within 30 days

Primary outcomes:
measure: Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants Who Experience 1 or More Gastrointestinal-related Adverse Events (AEs)
timeFrame: up to 14 weeks
measure: Percentage of Participants Who Experience 1 or More Gallbladder-related AEs
timeFrame: up to 14 weeks
measure: Percentage of Participants Who Experience 1 or More Allergic Reaction or Rash AEs
timeFrame: up to 14 weeks
measure: Percentage of Participants Who Experience 1 or More Hepatitis-related AEs
timeFrame: up to 14 weeks
measure: Percentage of Participants Who Experience Consecutive Elevations in Alanine Aminotransferase (ALT) ≥3 Times Upper Limit of Normal (ULN)
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Consecutive Elevations in Aspartate Aminotransferase (AST) ≥3 Times ULN
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Consecutive Elevations in ALT and/or AST ≥3 Times ULN
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Consecutive Elevations in ALT ≥5 Times ULN
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Consecutive Elevations in AST ≥5 Times ULN
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Have Consecutive Elevations in ALT and/or AST ≥5 Times ULN
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Consecutive Elevations in ALT ≥10 Times ULN
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Consecutive Elevations in AST ≥10 Times ULN
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Have Consecutive Elevations in ALT and/or AST ≥10 Times ULN
timeFrame: up to 12 weeks
measure: Percentage of Participants With Potential Hy's Law Condition
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Have Elevations in Creatine Kinase (CK) ≥10xULN
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Have Elevations in CK ≥10xULN With Muscle Symptoms
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Have Elevations in CK ≥10xULN and Drug-Related Muscle Symptoms
timeFrame: up to 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Teramoto T, Yokote K, Nishida C, Tershakovec AM, Oshima N, Takase T, Hirano T, Lee R, Johnson-Levonas AO. A phase III, clinical trial to study the efficacy and tolerability of ezetimibe plus atorvastatin combination therapy in Japanese patients with hypercholesterolemia: a randomized, double-blind comparative study. J Clin Therapeut Med. 2017;33(7):551-567