Dyslipidemia, Hypercholesterolemia
Conditions
Keywords
Hypercholesterolemia, Dyslipidemia
Brief summary
The purpose of this study is to determine the non-inferiority between two different FDC (fixed-dose combination), measuring LDL-Cholesterol levels, in high risk patients with primary hypercholesterolemia or mixed dyslipidemia.
Detailed description
The primary efficacy variable was the percentage of LDL-C variation at the end of nine weeks of treatment, compared to baseline (pre-randomization), in participants who achieved LDL \<100 mg/dL were considered to have been successfully treated.
Interventions
DRUGRosuvastatin 10 mg + Ezetimibe 10 mg and Rosuvastatin 20 mg + Ezetimibe 10 mg, according to clinical evaluation.
Tables containing: Rosuvastatin 10 mg + Ezetimibe 10 mg and Rosuvastatin 20 mg + Ezetimibe 10 mg, according to clinical evaluation.
DRUGSimvastatin 20 mg + Ezetimibe 10 mg and Simvastatin 40 mg + Ezetimibe 10 mg, according to clinical evaluation.
Tables containing: Simvastatin 20 mg + Ezetimibe 10 mg and Simvastatin 40 mg + Ezetimibe 10 mg, according to clinical evaluation.
Sponsors
Ache Laboratorios Farmaceuticos S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male and female participants aged 18 to 80 years; * Participants diagnosed with primary hypercholesterolemia or mixed dyslipidemia; * Participants must not have other clinically significant comorbidities that may interfere with study evaluations; * Participants able to understand and adhere to the therapeutic scheme and to attend the study visits; * Participants who agree to maintain a low cholesterol diet throughout the study; * Participants who agree to discontinue previous medication for hypercholesterolemia treatment throughout the study; * Participants with hypercholesterolemia or mixed dyslipidemia with the following laboratory test results on the baseline visit: LDL-C level \>130 mg/dl if were receiving prior treatment with statins; or LDL-C level \>100 mg/dl if were receiving prior treatment with first generation statins; or LDL ≥160 mg/dL and ≤220 mg/dL and triglycerides ≤350 mg/dL if were not in prior treatment with statins. * Female participants in reproductive age with negative serum beta-hCG test result in the baseline visit who agree to use acceptable contraceptive methods (oral contraceptives, injectable contraceptives, intrauterine device (IUD), hormonal implants, barrier methods, hormonal patch, tubal ligation or female participants who declare to perform non reproductive sexual practices); except surgically sterile (for example oophorectomy and hysterectomy), surgical sterilization or of the partner; or postmenopausal for at least one year; * Participants with laboratorial test results after treatment with Simvastatin 20 mg for four weeks with LDL-C level ≥100 mg/dl.
Exclusion criteria
* Heart failure class III or IV (NYHA- New York Heart Association); * Blood dyscrasia; * Unstable angina pectoris; * Myocardial infarction in the last 3 months; * Planning for CABG (coronary artery bypass graft), peripheral or carotid percutaneous intervention for the next 90 days; * Renal insufficiency: estimated Glomerular Filtration Rate (GFR) \< 30 ml/min/m2; * History of alcoholism that, at the investigator's discretion, could compromise the drug treatment compliance; * Participants with comorbidities that hinder the interpretation of results or contraindicate the lipid-lowering therapy \[uncontrolled hypothyroidism (thyroid-stimulating hormone \[TSH\] \> 8 mUI/mL); uncontrolled diabetes (Hemoglobin A1c \[HbA1c\] \> 8%); active hepatic disease; antiretroviral therapy for HIV, neoplasm (except for adequately treated skin cancer within the past 5 years), concomitant immunosuppressive therapy (transplant receivers and rheumatic disease); * Uncontrolled systemic arterial hypertension; * Hypersensitivity to any component of the investigational product; * Participant who has participated in clinical trial protocols in the last twelve (12) months (CNS Resolution 251 of August 7, 1997, Part III, sub-item J), unless the investigator considers that there may be a direct benefit to the patient; * Any observational finding (clinical/ physical evaluation), laboratory abnormality, disease or therapy that is interpreted by the investigator as a risk to the research participant's participation in the clinical trial; * Aspartate transaminase (AST) or alanine aminotransferase (ALT) more than two times the normal upper limit of the central laboratory reference range after treatment with Simvastatin 20 mg for four weeks; * Creatine phosphokinase (CPK) more than three times the normal upper limit of the central laboratory reference range after treatment with Simvastatin 20 mg for four weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of LDL Cholesterol Levels | Baseline compared to the end of 9 weeks of treatment | The primary efficacy variable was the percentage of LDL-C variation at the end of nine weeks of treatment, compared to baseline (pre-randomization), in participants who achieved LDL \<100 mg/dL were considered to have been successfully treated. |
Countries
Brazil
Participant flow
Recruitment details
Participants were recruited at 7 research centers between March 2013 and July 2014. The first participant was enrolled on March 21, 2013 and the last participant was enrolled in July, 2014.
Pre-assignment details
Of 637 recruited participants, 254 met eligibility criteria and were recruited in the run-in phase.The participants received Simvastatin 20 mg tablet orally once daily for 5 weeks in this period and 241 completed the run-in phase. Of the 241 participants, 129 were eligible for the treatment phase and randomized.
Participants by arm
| Arm | Count |
|---|---|
| Rosuvastatin + Ezetimibe Participants received Rosuvastatin 10 mg+ Ezetimibe 10 mg tablet orally once daily for 5 weeks and after a LDL evaluation if it level was \<100 mg/dL the dose was maintained for more 4 weeks. However, if the LDL-C levels was ≥100 mg/dL, the dose was adjusted to Rosuvastatin 20 mg+ Ezetimibe 10mg tablet orally once daily for more 4 weeks.
Rosuvastatin 10 mg + Ezetimibe 10 mg and Rosuvastatin 20 mg + Ezetimibe 10 mg, according to clinical evaluation.: Tables containing: Rosuvastatin 10 mg + Ezetimibe 10 mg and Rosuvastatin 20 mg + Ezetimibe 10 mg, according to clinical evaluation. | 66 |
| Simvastatin + Ezetimibe Participants received Simvastatin 20 mg+ Ezetimibe 10 mg tablet orally once daily for 5 weeks and after a LDL evaluation if it level was \<100 mg/dL the dose was maintained for more 4 weeks. However, if the LDL-C levels was ≥100 mg/dL, the dose was adjusted to Simvastatin 40 mg + Ezetimibe 10mg tablet orally once daily for more 4 weeks.
Simvastatin 20 mg + Ezetimibe 10 mg and Simvastatin 40 mg + Ezetimibe 10 mg, according to clinical evaluation.: Tables containing: Simvastatin 20 mg + Ezetimibe 10 mg and Simvastatin 40 mg + Ezetimibe 10 mg, according to clinical evaluation. | 63 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Non-adherence to medication | 4 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Simvastatin + Ezetimibe | Total | Rosuvastatin + Ezetimibe |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 22 Participants | 39 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 90 Participants | 49 Participants |
| Age, Continuous | 59.16 years STANDARD_DEVIATION 9.6 | 59.28 years STANDARD_DEVIATION 9.1 | 59.39 years STANDARD_DEVIATION 8.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 12 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 12 Participants | 21 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 45 Participants | 96 Participants | 51 Participants |
| Region of Enrollment Brazil | 63 Participants | 129 Participants | 66 Participants |
| Sex: Female, Male Female | 53 Participants | 108 Participants | 55 Participants |
| Sex: Female, Male Male | 10 Participants | 21 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 63 |
| other Total, other adverse events | 2 / 66 | 4 / 63 |
| serious Total, serious adverse events | 0 / 66 | 2 / 63 |
Outcome results
Primary
Reduction of LDL Cholesterol Levels
The primary efficacy variable was the percentage of LDL-C variation at the end of nine weeks of treatment, compared to baseline (pre-randomization), in participants who achieved LDL \<100 mg/dL were considered to have been successfully treated.
Time frame: Baseline compared to the end of 9 weeks of treatment
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Rosuvastatin + Ezetimibe | Reduction of LDL Cholesterol Levels | -39.45 percent change of LDL |
| Simvastatin + Ezetimibe | Reduction of LDL Cholesterol Levels | -29.13 percent change of LDL |
Comparison: Rosuvastatin + Ezetimibe versus Simvastatin + Ezetimibep-value: 0.001395% CI: [-16.94, -3.7]ANCOVA