Clinical trial NCT02460159: A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653C in Japanese Participants With Hypercholesterolemia (MK-0653C-384)
Official title: A Phase III, Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653C in Japanese Patients With Hypercholesterolemia Who Have Inadequate LDL-C Control on Ezetimibe or Atorvastatin Calcium Monotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Heterozygous Familial Hypercholesterolemia
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2015-06-02
Enrollment: 135
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the safety and tolerability of Ezetimibe (EZ) 10 mg/Atorvastatin (Atora) 10 mg and EZ 10mg/Atora 20 mg fixed-dose combination (FDC) in Japanese participants with hypercholesterolemia uncontrolled with monotherapy of Ezetimibe 10 mg or Atorvastatin up to 20 mg. There is no formal hypothesis for the study.


Eligibility criteria: Inclusion Criteria

* Japanese
* Outpatient with hypercholesterolemia
* Has familial hypercholesterolemia (FH) diagnosed per genetic testing or meets two or more of the below criteria based on Japan Atherosclerosis Society Guideline 2012 (JAS2012): Hyper low-density lipoprotein (LDL)-cholesterolemia (an untreated LDL-C level of ≥180mg/dL); tendon xanthoma (tendon xanthoma on the backs of the hands, elbows, knees, etc. or achilles tendon hypertrophy) or xanthoma tuberosum; family history of FH or premature coronary arterial disease (within the participant's second degree relatives)
* Females must be of 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 JAS 2012 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)
* 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: Percentage of Participants Who Experience 1 or More Adverse Event (AE)
timeFrame: up to 54 Weeks
measure: Percentage of Participants Who Experience 1 or More Gastrointestinal-related AEs
timeFrame: up to 54 weeks
measure: Percentage of Participants Who Experience 1 or More Gallbladder-related AEs
timeFrame: up to 54 weeks
measure: Percentage of Participants Who Experience 1 or More Allergic Reaction or Rash AEs
timeFrame: up to 54 weeks
measure: Percentage of Participants Who Experience 1 or More Hepatitis-related AEs
timeFrame: up to 54 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 52 weeks
measure: Percentage of Participants Who Experience Elevations in ALT or AST ≥5 Times ULN
timeFrame: up to 52 weeks
measure: Percentage of Participants Who Experience Elevations in ALT or AST ≥10 Times ULN
timeFrame: up to 52 weeks
measure: Percentage of Participants With Potential Hy's Law Condition
timeFrame: up to 52 weeks
measure: Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN
timeFrame: up to 52 weeks
measure: Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN With Muscle Symptoms
timeFrame: up to 52 weeks
measure: Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN and Drug-Related Muscle Symptoms
timeFrame: up to 52 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 A, Oshima N, Takase T, Hirano T. A Phase III open-label clinical trial to assess the long-term safety of ezetimibe and atorvastatin combination therapy in Japanese patients with hypercholesterolemia. J Clin Therapeut Med. 2017;33(8):655-670.