Hypercholesterolemia
Conditions
Brief summary
Evaluate the safety of the long-term (1 year) coadministration of ezetimibe and atorvastatin in participants with hypercholesterolemia who have not reached low density lipoprotein (LDL)-cholesterol target with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors.
Interventions
DRUGEzetimibe
Ezetimibe 10 mg once daily
DRUGatorvastatin
atorvastatin 20 mg once daily
Sponsors
Organon and Co
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with hypercholesterolemia who satisfy the following criteria: * Participants who have used any of the following 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (hereinafter referred to as statins) for 4 weeks or longer before the start of the observation period and whose low density lipoprotein (LDL)-cholesterol level during the treatment had not reached lipid management target * Age: 20 years of age or older (at the time of obtaining informed consent) * Sex: both males and females * Inpatient/outpatient: Out-patient
Exclusion criteria
* Participants for whom any of the following is applicable: * Participants whose fasted triglyceride level measured at the start of the observation period or the treatment period exceeds 500 mg/dL * Participants with homozygous familial hypercholesterolemia * Participants with creatine phosphokinase (CPK) \> 2x upper limit of normal (ULN) measured at the start of the observation period or the treatment period. * Participants with serious hepatic disorder, or participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2x ULN measured at the start of the observation period or the treatment period. * Participants with a history of hypersensitivity to any ingredient of ezetimibe tablets or atorvastatin tablets * Pregnant, nursing women, women who may be pregnant, or participants wishing to be pregnant during the study. * Participants 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 participant 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.) * Participants who are using cyclosporine from after the start of the observation period * Participants with a history of ezetimibe use * Participants with hyperlipidemia associated with the following diseases: * Hypothyroidism * Obstructive gall bladder or biliary disease * Chronic renal failure * Pancreatitis * Participants with hyperlipidemia associated with concomitant use of drugs having adverse effect on serum lipids, etc * Participants who have received an investigational drug within 4 weeks of the start of the observation period * Other participants deemed not appropriate for study entry by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 considered treatment-related was considered an adverse reaction. |
Participant flow
Pre-assignment details
Participants did not Complete the Study: 1. level below what was specified in inclusion criterion 2. level \>500 mg/dL at start of treatment 3. level \>2x upper limit of normal at start of treatment 4. level \>=3x upper limit of normal after start of treatment 5. Adverse reactions did not improve or resolve after dose reduction of atorvastatin
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe + Atorvastatin Ezetimibe 10 mg once daily + Atorvastatin 20 mg once daily | 146 |
| Total | 146 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 11 |
| Overall Study | Adverse reaction did not improve (5) | 4 |
| Overall Study | Did not meet inclusion criteria | 1 |
| Overall Study | Drop in low density lipoprotein (1) | 2 |
| Overall Study | Elevated alanine aminotransferase (3) | 1 |
| Overall Study | Elevated alanine aminotransferase (4) | 7 |
| Overall Study | Elevated triglyceride level (2) | 1 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Ezetimibe + Atorvastatin |
|---|---|
| Age, Customized | 146 Participants |
| Region of Enrollment Japan | 146 participants |
| Sex: Female, Male Female | 79 Participants |
| Sex: Female, Male Male | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 132 / 146 |
| serious Total, serious adverse events | 11 / 146 |
Outcome results
Primary
Number of Participants With Adverse Events and Adverse Reactions
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 considered treatment-related was considered an adverse reaction.
Time frame: Throughout 1 year of study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ezetimibe + Atorvastatin | Number of Participants With Adverse Events and Adverse Reactions | Adverse Events | 141 Participants |
| Ezetimibe + Atorvastatin | Number of Participants With Adverse Events and Adverse Reactions | Adverse Reactions | 61 Participants |