Clinical trial NCT02741245: A Study of the Efficacy and Safety of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-832)
Official title: A Phase III, Randomized, Active Comparator-controlled, Clinical Trial to Study the Efficacy and Safety of MK-0653H 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: 2016-04-18
Enrollment: 321
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 and tolerability of 2 dose levels of MK-0653H in Japanese participants. The primary hypotheses are that the administration of MK-0653H is safe and tolerable and that MK-0653H is superior to single entity of Ezetimibe and Rosuvastatin in percent reduction from baseline in low-density lipoprotein-cholesterol (LDL-C) after 12 weeks of treatment.


Eligibility criteria: Inclusion Criteria:

* Japanese
* Outpatient with hypercholesterolemia
* Female participant who is of reproductive potential has to 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
* Will maintain a stable diet that is consistent with the Japan Atherosclerosis Society Guideline 2012 (JAS 2012) for prevention of atherosclerotic cardiovascular diseases for the duration of the study

Exclusion Criteria:

* Uncontrolled hypertension (treated or untreated)
* Uncontrolled type 1 or type 2 diabetes mellitus
* History of coronary artery disease (CAD), CAD-equivalent disease
* Familial hypercholesterolemia or has undergone LDL apheresis
* Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins
* Has 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
* Currently following an excessive weight reduction diet
* Currently engages 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 Rosuvastatin
* 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: Percentage Change From Baseline in Low-density Lipoprotein-cholesterol (LDL-C)
timeFrame: Baseline and Week 12
measure: Percentage of Participants Who Experience at Least 1 Adverse Event (AE)
timeFrame: up to 14 weeks
measure: Percentage of Participants Who Had Study Drug Discontinued Due to Adverse Event
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience 1 or More Gastrointestinal-related 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 Normal Limit (ULN)
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Consecutive Elevations in Aspartate Aminotransferase (AST) ≥3 Times Upper Normal Limit (ULN)
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) ≥3 Times Upper Normal Limit (ULN)
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Elevation in Alanine Aminotransferase (ALT) ≥5 Times Upper Normal Limit (ULN)
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Elevation in Aspartate Aminotransferase (AST) ≥5 Times Upper Normal Limit (ULN)
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Elevation in Alanine Aminotransferase (ALT) ≥10 Times Upper Normal Limit (ULN)
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Elevation in Aspartate Aminotransferase (AST) ≥10 Times Upper Normal Limit (ULN)
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) ≥10 Times Upper Normal Limit (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 Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN With Muscle Symptoms
timeFrame: up to 12 weeks
measure: Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN 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, Oshima N, Takase T. A phase III clinical trial to study the efficacy and safety of ezetimibe plus rosuvastatin combination therapy in Japanese patients with hypercholesterolemia - A randomized, double-blind comparative study. J Clin Therapeut Med. 2017;33(11):881-896.