Coadministration of Ezetimibe and Simvastatin in Patients With Primary Hypercholesterolemia (P05457)
Study Details
Study Description
Brief Summary
Evaluate the safety of the long-term (1 year) coadministration of ezetimibe and simvastatin in patients with hypercholesterolemia who have not reached low density lipoprotein (LDL)-cholesterol target with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Ezetimibe + Simvastatin Ezetimibe 10 mg + Simvastatin 20 mg |
Drug: Ezetimibe
Ezetimibe 10 mg once daily
Other Names:
Drug: Simvastatin
Simvastatin 20 mg daily
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events and Adverse Reactions [Throughout 1 year of study]
An adverse event is any unfavorable medical event occurring in a subject to whom an investigational product is administered, and a causal relationship between the administered investigational product and an adverse event is not always clarified. That is, an adverse event is any unfavorable or unintended sign (including an abnormal change in laboratory test values), symptom, or disease, and a causal relationship to the relevant investigational product is not considered. Any adverse event that was treatment-related was considered an adverse reaction.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with hypercholesterolemia who satisfy the following criteria:
-
Patients who have used any of the following HMG-CoA reductase inhibitors (hereinafter referred to as "statins") for 4 weeks or longer before the start of the observation period and whose LDL-cholesterol level during the treatment had not reached lipid management target indicated below
-
Age: 20 years of age or older (at the time of obtaining informed consent)
-
Sex: both males and females
-
Inpatient/outpatient: Out-patients
Exclusion Criteria:
-
Patients for whom any of the following is applicable:
-
Patients whose fasted triglyceride level measured at the start of the observation period or the treatment period exceeds 500 mg/dL
-
Patients with homozygous familial hypercholesterolemia
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Patients with creatine phosphokinase (CPK) > 2x upper limit of normal (ULN) measured at the start of the observation period or the treatment period.
-
Patients with serious hepatic disorder, or patients with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x ULN measured at the start of the observation period or the treatment period.
-
Patients with a history of hypersensitivity to any ingredient of ezetimibe tablets or simvastatin tablets
-
Pregnant, nursing women, women who may be pregnant, or patients wishing to be pregnant during the study.
-
Patients who have discontinued use of serum lipid lowering agents for less than 4 weeks at the start of the treatment period (8 weeks in the case of probucol). (However, if the patient had taken a serum lipid lowering agent before the test conducted at the start of the observation period, a period of discontinuation of 27 days, or 55 days in the case of probucol, is allowed.)
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Patients who are using cyclosporine from after the start of the observation period
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Patients who are using any of the following drug from after the start of the observation period: itraconazole, miconazole, atazanavir, saquinavir mesilate
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Patients with a history of ezetimibe use
-
Patients with hyperlipidemia associated with the following diseases:
-
Hypothyroidism
-
Obstructive gall bladder or biliary disease
-
Chronic renal failure
-
Pancreatitis
-
Patients with hyperlipidemia associated with concomitant use of drugs having adverse effect on serum lipids, etc
-
Patients who have received an investigational drug within 4 weeks of the start of the observation period
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Other patients deemed not appropriate for study entry by the investigator
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Organon and Co
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- P05457
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Ezetimibe + Simvastatin |
---|---|
Arm/Group Description | Ezetimibe 10 mg + Simvastatin 20 mg level below what was specified in inclusion criterion level >2x upper limit of normal at start of treatment level >=3x upper limit of normal after start of treatment did not resolve or improve after dose reduction of simvastatin |
Period Title: Overall Study | |
STARTED | 151 |
COMPLETED | 132 |
NOT COMPLETED | 19 |
Baseline Characteristics
Arm/Group Title | Ezetimibe + Simvastatin |
---|---|
Arm/Group Description | Ezetimibe 10 mg + Simvastatin 20 mg |
Overall Participants | 151 |
Age, Customized (Number) [Number] | |
Number [Participants] |
151
100%
|
Sex: Female, Male (Count of Participants) | |
Female |
82
54.3%
|
Male |
69
45.7%
|
Region of Enrollment (participants) [Number] | |
Japan |
151
100%
|
Outcome Measures
Title | Number of Participants With Adverse Events and Adverse Reactions |
---|---|
Description | An adverse event is any unfavorable medical event occurring in a subject to whom an investigational product is administered, and a causal relationship between the administered investigational product and an adverse event is not always clarified. That is, an adverse event is any unfavorable or unintended sign (including an abnormal change in laboratory test values), symptom, or disease, and a causal relationship to the relevant investigational product is not considered. Any adverse event that was treatment-related was considered an adverse reaction. |
Time Frame | Throughout 1 year of study |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Ezetimibe + Simvastatin |
---|---|
Arm/Group Description | Ezetimibe 10 mg + Simvastatin 20 mg |
Measure Participants | 151 |
Adverse Events |
143
94.7%
|
Adverse Reactions |
36
23.8%
|
Adverse Events
Time Frame | ||
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Ezetimibe+Simvastatin | |
Arm/Group Description | ||
All Cause Mortality |
||
Ezetimibe+Simvastatin | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
Ezetimibe+Simvastatin | ||
Affected / at Risk (%) | # Events | |
Total | 17/151 (11.3%) | |
Cardiac disorders | ||
ACUTE MYOCARDIAL INFARCTION | 1/151 (0.7%) | 1 |
ANGINA UNSTABLE | 1/151 (0.7%) | 1 |
HYPERTROPHIC CARDIOMYOPATHY | 1/151 (0.7%) | 1 |
Eye disorders | ||
EYE PAIN | 1/151 (0.7%) | 1 |
Infections and infestations | ||
PNEUMONIA | 1/151 (0.7%) | 1 |
Injury, poisoning and procedural complications | ||
CORONARY ARTERY RESTENOSIS | 3/151 (2%) | 3 |
IN-STENT CORONARY ARTERY RESTENOSIS | 1/151 (0.7%) | 2 |
Metabolism and nutrition disorders | ||
DIABETES MELLITUS INADEQUATE CONTROL | 1/151 (0.7%) | 1 |
Musculoskeletal and connective tissue disorders | ||
ROTATOR CUFF SYNDROME | 1/151 (0.7%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
BREAST CANCER | 1/151 (0.7%) | 1 |
UTERINE CANCER | 1/151 (0.7%) | 1 |
Nervous system disorders | ||
SUBARACHNOID HAEMORRHAGE | 1/151 (0.7%) | 1 |
Skin and subcutaneous tissue disorders | ||
ACTINIC KERATOSIS | 1/151 (0.7%) | 1 |
Surgical and medical procedures | ||
ARTERIAL STENT INSERTION | 1/151 (0.7%) | 2 |
Vascular disorders | ||
AORTIC DISSECTION | 1/151 (0.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||
Ezetimibe+Simvastatin | ||
Affected / at Risk (%) | # Events | |
Total | 127/151 (84.1%) | |
Gastrointestinal disorders | ||
CONSTIPATION | 9/151 (6%) | 9 |
Infections and infestations | ||
BRONCHITIS | 20/151 (13.2%) | 25 |
NASOPHARYNGITIS | 46/151 (30.5%) | 73 |
PHARYNGITIS | 10/151 (6.6%) | 13 |
Investigations | ||
ALANINE AMINOTRANSFERASE INCREASED | 26/151 (17.2%) | 32 |
ASPARTATE AMINOTRANSFERASE INCREASED | 10/151 (6.6%) | 11 |
BLOOD AMYLASE INCREASED | 12/151 (7.9%) | 14 |
BLOOD CREATINE PHOSPHOKINASE INCREASED | 27/151 (17.9%) | 33 |
C-REACTIVE PROTEIN INCREASED | 41/151 (27.2%) | 47 |
GAMMA-GLUTAMYLTRANSFERASE INCREASED | 14/151 (9.3%) | 14 |
GLYCOSYLATED HAEMOGLOBIN INCREASED | 10/151 (6.6%) | 11 |
MYOGLOBIN BLOOD INCREASED | 21/151 (13.9%) | 21 |
WHITE BLOOD CELL COUNT INCREASED | 12/151 (7.9%) | 12 |
Metabolism and nutrition disorders | ||
DIABETES MELLITUS | 8/151 (5.3%) | 8 |
HYPOGLYCAEMIA | 9/151 (6%) | 14 |
Musculoskeletal and connective tissue disorders | ||
ARTHRALGIA | 15/151 (9.9%) | 15 |
BACK PAIN | 17/151 (11.3%) | 17 |
MUSCLE SPASMS | 14/151 (9.3%) | 20 |
MUSCULOSKELETAL STIFFNESS | 13/151 (8.6%) | 14 |
PAIN IN EXTREMITY | 11/151 (7.3%) | 12 |
Nervous system disorders | ||
HEADACHE | 12/151 (7.9%) | 14 |
Respiratory, thoracic and mediastinal disorders | ||
UPPER RESPIRATORY TRACT INFLAMMATION | 11/151 (7.3%) | 13 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Principal Investigator (PI) agrees, for a period of 5 years following the Effective Date, to retain the Disclosure made to it by or on behalf of Sponsor (SPKK), in confidence and not to disclose it to any third party. PI further agrees that during such time period it will not, either directly or indirectly, use the Disclosure for any purpose(s) other than that indicated herein without the prior written consent of SPKK.
Results Point of Contact
Name/Title | Senior Vice President, Global Clinical Development |
---|---|
Organization | Merck Sharp & Dohme Corp. |
Phone | |
ClinicalTrialsDisclosure@merck.com |
- P05457