Back to resultsA Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653C in Japanese Participants With Hypercholesterolemia (MK-0653C-384)
Primary Purpose
Hypercholesterolemia, Heterozygous Familial Hypercholesterolemia
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
EZ 10 mg/Atorva 20 mg FDC
EZ 10 mg/Atorva 10 mg FDC
Sponsored by
About this trial
This is an interventional treatment trial for Hypercholesterolemia
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
EZ 10 mg/Atorva 10 mg FDC
EZ 10 mg/Atorva 20 mg FDC
Arm Description
one EZ 10 mg/Atorva 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.
one EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants Who Experience 1 or More Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized.
Percentage of Participants Who Experience 1 or More Gastrointestinal-related AEs
Gastrointestinal-related AEs included all preferred terms within system organ class of Gastrointestinal Disorders except Chapped Lips and Toothache.
Percentage of Participants Who Experience 1 or More Gallbladder-related AEs
Gallbladder-related AEs included Bile Duct Obstruction, Bile Duct Stone, Bile Duct Stenosis, Biliary Colic, Cholangitis, Cholecystectomy, Cholecystitis, Cholelithiasis, Gallbladder Disorder, Gallbladder Perforation, Hepatic Pain, and Hydrocholecystis.
Percentage of Participants Who Experience 1 or More Allergic Reaction or Rash AEs
Allergic Reaction or Rash AEs included Allergy to Arthropod Sting, Anaphylactoid Reaction, Anaphylactic Reaction, Anaphylatic Shock, Anaphylactoid Shock, Angioedema, Conjunctivitis Allergic, Contrast Media Reaction, Dermatitis, Dermatitis Allergic, Dermatitis Atopic, Dermatitis Bullous, Dermatitis Contact, Dermatitis Psoriasiform, Drug Hypersensitivity, Eczema, Eosinophila, Erythema, Eye Allergy, Face Oedema, Hypersensitivity, Mechanical Urticaria, Palmar Erythema, Periorbital Oedema, Photodermatosis, Photosensitivity Allergic reaction, Photosensitivity Reaction, Pigmentation Disorder, Pruritus, Pruritus Generalised, Rash, Rash Erythematous, Rash Follicular, Rash Generalised, Rash Maculo-Papular, Rash Papulosquamous, Rash Pruritic, Rash Pustular, Rash Vesicular, Rhinitis, Rhinitis Allergic, Rosacea, Skin Exfoliation, Skin Disorder, Skin Hyperpigmentation, Skin Lesion, Skin Mass, Skin Ulcer, Subcutaneous Nodule, Swelling Face, Systemic Lupus Erythematosus Rash, Urticaria.
Percentage of Participants Who Experience 1 or More Hepatitis-related AEs
Hepatitis-related AEs included Cholestasis, Cytolytic Hepatitis, Hepatic Cyst, Hepatic Failure, Hepatic Lesion, Hepatic Necrosis, Hepatitis, Hepatitis Cholestatic, Hepatitis Fulminant, Hepatitis Infectious, Hepatocellular Injury, Hepatomegaly, Jaundice, Jaundice Cholestatic.
Percentage of Participants Who Experience Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) ≥3 Times Upper Normal Limit (ULN)
Participants had ALT and AST levels assessed throughout the 52 week treatment period. Participants who had 2 consecutive assessments of ALT and/or AST that were 3 x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Percentage of Participants Who Experience Elevations in ALT or AST ≥5 Times ULN
Participants had ALT and AST levels assessed throughout the 52 week treatment period. Participants who had assessments of ALT or AST that were 5x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Percentage of Participants Who Experience Elevations in ALT or AST ≥10 Times ULN
Participants had ALT and AST levels assessed throughout the 52 week treatment period. Participants who had assessments of ALT and/or AST that were 10x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Percentage of Participants With Potential Hy's Law Condition
Percentage of Participants with Potential Hy's Law Condition (defined as serum ALT or serum AST elevations >3xULN, with serum alkaline phosphatase <2xULN and total bilirubin (TBL) ≥2xULN) was summarized. The ALT and AST ULNs were 40 U/L. The ULN for alkaline phosphatase was 359 IU/L and the ULN for total bilirubin was 1.2 mg/dL.
Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN
Participants had creatine phosphokinase (CK) levels assessed throughout the 12 week treatment period. Participants who had any CK level that was ≥10 x ULN were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN With Muscle Symptoms
Participants had CK levels assessed throughout the 52 week treatment period. Participants who had any CK level that was ≥10 x ULN and had associated muscle symptoms present within +/- 7 days were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN and Drug-Related Muscle Symptoms
Participants had CK levels assessed throughout the 52 week treatment period. Participants who had any CK level that was ≥10 x ULN and had associated muscle symptoms present within +/- 7 days that were reported as at least possibly-related to study drug were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02460159
Brief Title
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
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
June 23, 2015 (Actual)
Primary Completion Date
December 22, 2016 (Actual)
Study Completion Date
December 22, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Organon and Co
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia, Heterozygous Familial Hypercholesterolemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
135 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EZ 10 mg/Atorva 10 mg FDC
Arm Type
Experimental
Arm Description
one EZ 10 mg/Atorva 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.
Arm Title
EZ 10 mg/Atorva 20 mg FDC
Arm Type
Experimental
Arm Description
one EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Intervention Type
Drug
Intervention Name(s)
EZ 10 mg/Atorva 20 mg FDC
Other Intervention Name(s)
MK-0653C
Intervention Type
Drug
Intervention Name(s)
EZ 10 mg/Atorva 10 mg FDC
Other Intervention Name(s)
MK-0653C
Primary Outcome Measure Information:
Title
Percentage of Participants Who Experience 1 or More Adverse Event (AE)
Description
An AE was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized.
Time Frame
up to 54 Weeks
Title
Percentage of Participants Who Experience 1 or More Gastrointestinal-related AEs
Description
Gastrointestinal-related AEs included all preferred terms within system organ class of Gastrointestinal Disorders except Chapped Lips and Toothache.
Time Frame
up to 54 weeks
Title
Percentage of Participants Who Experience 1 or More Gallbladder-related AEs
Description
Gallbladder-related AEs included Bile Duct Obstruction, Bile Duct Stone, Bile Duct Stenosis, Biliary Colic, Cholangitis, Cholecystectomy, Cholecystitis, Cholelithiasis, Gallbladder Disorder, Gallbladder Perforation, Hepatic Pain, and Hydrocholecystis.
Time Frame
up to 54 weeks
Title
Percentage of Participants Who Experience 1 or More Allergic Reaction or Rash AEs
Description
Allergic Reaction or Rash AEs included Allergy to Arthropod Sting, Anaphylactoid Reaction, Anaphylactic Reaction, Anaphylatic Shock, Anaphylactoid Shock, Angioedema, Conjunctivitis Allergic, Contrast Media Reaction, Dermatitis, Dermatitis Allergic, Dermatitis Atopic, Dermatitis Bullous, Dermatitis Contact, Dermatitis Psoriasiform, Drug Hypersensitivity, Eczema, Eosinophila, Erythema, Eye Allergy, Face Oedema, Hypersensitivity, Mechanical Urticaria, Palmar Erythema, Periorbital Oedema, Photodermatosis, Photosensitivity Allergic reaction, Photosensitivity Reaction, Pigmentation Disorder, Pruritus, Pruritus Generalised, Rash, Rash Erythematous, Rash Follicular, Rash Generalised, Rash Maculo-Papular, Rash Papulosquamous, Rash Pruritic, Rash Pustular, Rash Vesicular, Rhinitis, Rhinitis Allergic, Rosacea, Skin Exfoliation, Skin Disorder, Skin Hyperpigmentation, Skin Lesion, Skin Mass, Skin Ulcer, Subcutaneous Nodule, Swelling Face, Systemic Lupus Erythematosus Rash, Urticaria.
Time Frame
up to 54 weeks
Title
Percentage of Participants Who Experience 1 or More Hepatitis-related AEs
Description
Hepatitis-related AEs included Cholestasis, Cytolytic Hepatitis, Hepatic Cyst, Hepatic Failure, Hepatic Lesion, Hepatic Necrosis, Hepatitis, Hepatitis Cholestatic, Hepatitis Fulminant, Hepatitis Infectious, Hepatocellular Injury, Hepatomegaly, Jaundice, Jaundice Cholestatic.
Time Frame
up to 54 weeks
Title
Percentage of Participants Who Experience Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) ≥3 Times Upper Normal Limit (ULN)
Description
Participants had ALT and AST levels assessed throughout the 52 week treatment period. Participants who had 2 consecutive assessments of ALT and/or AST that were 3 x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Time Frame
up to 52 weeks
Title
Percentage of Participants Who Experience Elevations in ALT or AST ≥5 Times ULN
Description
Participants had ALT and AST levels assessed throughout the 52 week treatment period. Participants who had assessments of ALT or AST that were 5x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Time Frame
up to 52 weeks
Title
Percentage of Participants Who Experience Elevations in ALT or AST ≥10 Times ULN
Description
Participants had ALT and AST levels assessed throughout the 52 week treatment period. Participants who had assessments of ALT and/or AST that were 10x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Time Frame
up to 52 weeks
Title
Percentage of Participants With Potential Hy's Law Condition
Description
Percentage of Participants with Potential Hy's Law Condition (defined as serum ALT or serum AST elevations >3xULN, with serum alkaline phosphatase <2xULN and total bilirubin (TBL) ≥2xULN) was summarized. The ALT and AST ULNs were 40 U/L. The ULN for alkaline phosphatase was 359 IU/L and the ULN for total bilirubin was 1.2 mg/dL.
Time Frame
up to 52 weeks
Title
Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN
Description
Participants had creatine phosphokinase (CK) levels assessed throughout the 12 week treatment period. Participants who had any CK level that was ≥10 x ULN were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
Time Frame
up to 52 weeks
Title
Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN With Muscle Symptoms
Description
Participants had CK levels assessed throughout the 52 week treatment period. Participants who had any CK level that was ≥10 x ULN and had associated muscle symptoms present within +/- 7 days were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
Time Frame
up to 52 weeks
Title
Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN and Drug-Related Muscle Symptoms
Description
Participants had CK levels assessed throughout the 52 week treatment period. Participants who had any CK level that was ≥10 x ULN and had associated muscle symptoms present within +/- 7 days that were reported as at least possibly-related to study drug were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
Time Frame
up to 52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
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.
Results Reference
result
Learn more about this trial
A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653C in Japanese Participants With Hypercholesterolemia (MK-0653C-384)
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