Dyslipidemia
Conditions
Keywords
Fibrates, Dyslipidemia
Brief summary
This is a double-blind, randomized study designed to compare the efficacy and safety of two fixed combinations of fenofibrate / simvastatin 145/20 mg and fenofibrate / simvastatin 145/40 mg tablets vs. matching monotherapies in subjects with abnormal fat (lipids) in the blood and at high risk of cardiovascular disease. Fenofibrate is a treatment that lowers fat in blood. It is prescribed in patients with high levels of triglycerides (TG). The drug has been marketed in more than 80 countries since 1975. Simvastatin is also used for the treatment of patients with a high level of cholesterol. These have also been marketed worldwide for more than 20 years. It is important to treat high levels of fats in the blood because it has been shown that even mildly elevated level of lipids in the blood can lead to diseases of the blood vessels. It has been shown in several studies and in clinical practice that the combination of fenofibrate plus simvastatin can lead to improved effects on blood fats, compared to treatment with simvastatin or fenofibrate alone. The main objective of the study is to compare the efficacy of the two fixed-combinations (FC) -fenofibrate/simvastatin 145/20 mg tablet and fenofibrate/simvastatin 145/40 mg tablet in reducing TG and increasing high density lipoprotein cholesterol (HDL-C) versus simvastatin 20 mg or 40 mg, and in reducing low density lipoprotein cholesterol (LDL-C) versus fenofibrate 145 mg.
Interventions
DRUGFixed Combination of Fenofibrate/simvastatin 145/20 mg
Fenofibrate/simvastatin oval biconvex film-coated tablet, 145 mg / 20 mg, once daily, 12 weeks
Simvastatin generic tablet over-encapsulated, 20 mg, once daily, 12 weeks
Fenofibrate, tablet, 145 mg, once daily, 12 weeks
DRUGFixed Combination of Fenofibrate/simvastatin 145/40 mg
Fenofibrate/simvastatin film-coated tablet 145 mg / 40 mg, once daily, 12 weeks
simvastatin, generic tablet over-encapsulated, 40 mg, once daily, 12 weeks
Sponsors
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Either gender (tentatively 50 percent females to be included and if of childbearing potential she must agree to use medically acceptable methods of contraception from the time of signing the informed consent until 7 days following administration of the last treatment or dose of study medication). Accepted contraceptive methods are implants, injectables, combined oral contraceptives, intra-uterine device or sexual abstinence. 2. between 18 (inclusive) and 80 years 3. With mixed dyslipidemia with fasting lipid results of a blood sample taken at inclusion and after at least 3 months of any statin monotherapy (excluding simvastatin 80 mg, atorvastatin 40 mg and 80 mg, rosuvastatin 20 mg and 40 mg): * TG higher than/equal to 1.71 mmol/L (higher than/equal to 150 mg/dL) and * LDL-C higher or equal to 1.81 mmol/L (higher or equal 70 mg/dL) but smaller than/equal to 3.36 mmol/L (smaller than/equal to 130 mg/dL) 4. High risk or very high risk based on known CardioVascular Disease (CVD) or type 2 diabetes or type 1 diabetes with microalbuminuria or a Systematic Coronary Risk Estimation (SCORE) chart risk ≥ 5percent 5. Aspartate aminotransferase and/or alanine aminotransferase smaller than/equal to 2 times the Upper Normal of Limit (UNL)
Exclusion criteria
1. Known hypersensitivity to fibrates or simvastatin or known photoallergic or phototoxic reactions under treatment with fibrates or ketoprofen or known allergic reactions caused by peanuts, peanuts or arachis oil or soy lecithin, or related products, 2. Pregnant or lactating women, 3. Unable or unwilling to comply with the protocol and the recommended diet, 4. Likely to withdraw from the study before its completion, 5. Having received an investigational drug or vaccine in the last 30 days before date of inclusion, or still participating in such a trial at Visit 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Change of TG (Triglyceride) | from baseline to 12 weeks of treatment | Collection and measurement of blood samples. |
| Percentage of Change of HDL-C (High Density Lipoprotein Cholesterol) | from baseline to 12 weeks of treatment | Collection and measurement of blood samples. |
| Percentage of Change of LDL-C (Low Density Lipoprotein Cholesterol) | from baseline to 12 weeks of treatment | Collection and measurement of blood samples. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Non-HDL (High Density Lipoprotein)-C From Baseline | 12 weeks | Collection and measurement of blood samples |
| Percentage of TC (Triglyceride) From Baseline | 12 weeks | Collection and measurement of blood samples |
| Percentage of Apolipoprotein AI From Baseline | 12 weeks | Collection and measurement of blood samples |
| Percentage of Apolipoprotein B From Baseline | 12 weeks | Collection and measurement of blood samples |
| Percentage of High-sensitivity C-reactive Protein (hsCRP) From Baseline | 12 weeks | Collection and measurement of blood samples |
| Percentage of Subjects Meeting Target Levels of Lipids (According to Very High or High Risk) | 12 weeks | Collection and measurement of blood samples |
| Adverse Events | 12 weeks | Collection and measurement of blood samples |
| Creatine Kinase (CK) | 12 weeks | Collection and measurement of blood samples |
| Alanine Aminotransferase (ALT) | 12 weeks | Collection and measurement of blood samples |
| Plasma Creatinine | 12 weeks | Collection and measurement of blood samples |
| Total Bilirubin | 12 weeks | Collection and measurement of blood samples |
| Cystatin C | 12 weeks | Collection and measurement of blood samples |
Countries
Argentina, Czechia, Germany, Mexico, Poland, Romania, Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fenofibrate/Simvastatin 145/20 mg Fenofibrate/simvastatin 145/20 mg: Fenofibrate/simvastatin oval biconvex film-coated tablet, 145 mg / 20 mg, once daily, 12 weeks | 109 |
| Simvastatin 20 mg Simvastatin 20 mg: Simvastatin generic tablet over-encapsulated, 20 mg, once daily, 12 weeks | 114 |
| Fenofibrate/Simvastatin 145/40 mg Fenofibrate/simvastatin 145/40 mg: Fenofibrate/simvastatin film-coated tablet 145 mg / 40 mg, once daily, 12 weeks | 110 |
| Simvastatin 40 mg Simvastatin 40 mg: simvastatin, generic tablet over-encapsulated, 40 mg, once daily, 12 weeks | 112 |
| Fenofibrate 145 mg Fenofibrate 145 mg: Fenofibrate, tablet, 145 mg, once daily, 12 weeks | 111 |
| Total | 556 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Administrative | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Adverse Event | 5 | 6 | 3 | 4 | 6 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 5 | 4 | 3 |
Baseline characteristics
| Characteristic | Fenofibrate/Simvastatin 145/20 mg | Total | Fenofibrate 145 mg | Simvastatin 40 mg | Fenofibrate/Simvastatin 145/40 mg | Simvastatin 20 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 59.6 years STANDARD_DEVIATION 10 | 60.0 years STANDARD_DEVIATION 9.1 | 60.4 years STANDARD_DEVIATION 9 | 59.3 years STANDARD_DEVIATION 9.1 | 60.4 years STANDARD_DEVIATION 8.1 | 60.5 years STANDARD_DEVIATION 9.3 |
| HDL Cholesterol (mmol/L) | 1.1 mmol/L STANDARD_DEVIATION 0.3 | 1.2 mmol/L STANDARD_DEVIATION 0.3 | 1.2 mmol/L STANDARD_DEVIATION 0.3 | 1.2 mmol/L STANDARD_DEVIATION 0.3 | 1.2 mmol/L STANDARD_DEVIATION 0.3 | 1.2 mmol/L STANDARD_DEVIATION 0.3 |
| LDL Cholesterol (mmol/L) | 2.6 mmol/L STANDARD_DEVIATION 0.5 | 2.7 mmol/L STANDARD_DEVIATION 0.5 | 2.7 mmol/L STANDARD_DEVIATION 0.5 | 2.7 mmol/L STANDARD_DEVIATION 0.4 | 2.6 mmol/L STANDARD_DEVIATION 0.4 | 2.6 mmol/L STANDARD_DEVIATION 0.4 |
| Region of Enrollment Argentina | 19 participants | 101 participants | 21 participants | 20 participants | 19 participants | 22 participants |
| Region of Enrollment Czech Republic | 22 participants | 110 participants | 21 participants | 23 participants | 22 participants | 22 participants |
| Region of Enrollment Germany | 30 participants | 154 participants | 33 participants | 31 participants | 31 participants | 29 participants |
| Region of Enrollment Mexico | 7 participants | 39 participants | 8 participants | 7 participants | 8 participants | 9 participants |
| Region of Enrollment Poland | 7 participants | 41 participants | 7 participants | 10 participants | 8 participants | 9 participants |
| Region of Enrollment Romania | 6 participants | 27 participants | 4 participants | 5 participants | 6 participants | 6 participants |
| Region of Enrollment Russian Federation | 18 participants | 84 participants | 17 participants | 16 participants | 16 participants | 17 participants |
| Sex: Female, Male Female | 38 Participants | 198 Participants | 38 Participants | 39 Participants | 43 Participants | 40 Participants |
| Sex: Female, Male Male | 71 Participants | 358 Participants | 73 Participants | 73 Participants | 67 Participants | 74 Participants |
| Triglycerides (mmol/L) | 2.8 mmol/L STANDARD_DEVIATION 1.1 | 2.7 mmol/L STANDARD_DEVIATION 1.1 | 2.9 mmol/L STANDARD_DEVIATION 1.3 | 2.7 mmol/L STANDARD_DEVIATION 1 | 2.7 mmol/L STANDARD_DEVIATION 1.4 | 2.5 mmol/L STANDARD_DEVIATION 1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 111 | 7 / 117 | 4 / 113 | 9 / 115 | 15 / 112 |
| serious Total, serious adverse events | 3 / 111 | 3 / 117 | 3 / 113 | 1 / 115 | 3 / 112 |
Outcome results
Primary
Percentage of Change of HDL-C (High Density Lipoprotein Cholesterol)
Collection and measurement of blood samples.
Time frame: from baseline to 12 weeks of treatment
Population: The Primary Analysis was done for the sample set of patients with 12 weeks' assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate/Simvastatin 145/20 mg | Percentage of Change of HDL-C (High Density Lipoprotein Cholesterol) | 9.0 percentage of change | Standard Deviation 16.8 |
| Simvastatin 20 mg | Percentage of Change of HDL-C (High Density Lipoprotein Cholesterol) | 0.3 percentage of change | Standard Deviation 12.1 |
| Fenofibrate/Simvastatin 145/40 mg | Percentage of Change of HDL-C (High Density Lipoprotein Cholesterol) | 8.8 percentage of change | Standard Deviation 16.5 |
| Simvastatin 40 mg | Percentage of Change of HDL-C (High Density Lipoprotein Cholesterol) | 2.2 percentage of change | Standard Deviation 12.5 |
| Fenofibrate 145 mg | Percentage of Change of HDL-C (High Density Lipoprotein Cholesterol) | 7.6 percentage of change | Standard Deviation 15.7 |
Primary
Percentage of Change of LDL-C (Low Density Lipoprotein Cholesterol)
Collection and measurement of blood samples.
Time frame: from baseline to 12 weeks of treatment
Population: The Primary Analysis was done for the sample set of patients with 12 weeks' assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate/Simvastatin 145/20 mg | Percentage of Change of LDL-C (Low Density Lipoprotein Cholesterol) | 1.9 percentage of change | Standard Deviation 25.4 |
| Simvastatin 20 mg | Percentage of Change of LDL-C (Low Density Lipoprotein Cholesterol) | -2.0 percentage of change | Standard Deviation 24.8 |
| Fenofibrate/Simvastatin 145/40 mg | Percentage of Change of LDL-C (Low Density Lipoprotein Cholesterol) | -6.1 percentage of change | Standard Deviation 26.2 |
| Simvastatin 40 mg | Percentage of Change of LDL-C (Low Density Lipoprotein Cholesterol) | -8.1 percentage of change | Standard Deviation 25.8 |
| Fenofibrate 145 mg | Percentage of Change of LDL-C (Low Density Lipoprotein Cholesterol) | 30.3 percentage of change | Standard Deviation 35.6 |
Primary
Percentage of Change of TG (Triglyceride)
Collection and measurement of blood samples.
Time frame: from baseline to 12 weeks of treatment
Population: The Primary Analysis was done for the sample set of patients with 12 weeks' assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate/Simvastatin 145/20 mg | Percentage of Change of TG (Triglyceride) | -30.6 percentage of change | Standard Deviation 25.8 |
| Simvastatin 20 mg | Percentage of Change of TG (Triglyceride) | 10.7 percentage of change | Standard Deviation 48.8 |
| Fenofibrate/Simvastatin 145/40 mg | Percentage of Change of TG (Triglyceride) | -27.3 percentage of change | Standard Deviation 35.9 |
| Simvastatin 40 mg | Percentage of Change of TG (Triglyceride) | -2.9 percentage of change | Standard Deviation 34.3 |
| Fenofibrate 145 mg | Percentage of Change of TG (Triglyceride) | -21.6 percentage of change | Standard Deviation 34.2 |
Secondary
Adverse Events
Collection and measurement of blood samples
Time frame: 12 weeks
Secondary
Alanine Aminotransferase (ALT)
Collection and measurement of blood samples
Time frame: 12 weeks
Secondary
Creatine Kinase (CK)
Collection and measurement of blood samples
Time frame: 12 weeks
Secondary
Cystatin C
Collection and measurement of blood samples
Time frame: 12 weeks
Secondary
Percentage of Apolipoprotein AI From Baseline
Collection and measurement of blood samples
Time frame: 12 weeks
Secondary
Percentage of Apolipoprotein B From Baseline
Collection and measurement of blood samples
Time frame: 12 weeks
Secondary
Percentage of High-sensitivity C-reactive Protein (hsCRP) From Baseline
Collection and measurement of blood samples
Time frame: 12 weeks
Secondary
Percentage of Non-HDL (High Density Lipoprotein)-C From Baseline
Collection and measurement of blood samples
Time frame: 12 weeks
Secondary
Percentage of Subjects Meeting Target Levels of Lipids (According to Very High or High Risk)
Collection and measurement of blood samples
Time frame: 12 weeks
Secondary
Percentage of TC (Triglyceride) From Baseline
Collection and measurement of blood samples
Time frame: 12 weeks
Secondary
Plasma Creatinine
Collection and measurement of blood samples
Time frame: 12 weeks
Secondary
Total Bilirubin
Collection and measurement of blood samples
Time frame: 12 weeks