Hypercholesterolemia
Conditions
Brief summary
To evaluate the efficacy and safety of ezetimibe/simvastatin and niacin in patients with high cholesterol.
Interventions
DRUGComparator: ezetimibe/simvastatin + niacin (ER)
ezetimibe/simvastatin 10/20mg tablet + niacin (ER) tablet, titrating to 2g, po qd. Treatment time will be \ 24 weeks
DRUGComparator: Placebo to ezetimibe/simvastatin
ezetimibe/simvastatin (Pbo) tablet. Treatment time will be \ 24 weeks.
DRUGComparator: niacin (ER) tablet
niacin (ER) tablet, titrating to 2g, po qd. Treatment time will be \ 24 weeks
DRUGComparator: ezetimibe (+) simvastatin
ezetimibe/simvastatin 10/20mg tablet. Treatment time will be \ 24 weeks.
DRUGComparator: Placebo to Niacin (ER)
Niacin (ER) (Pbo) tablet. Treatment time will be \ 24 weeks.
DRUGComparator: ezetimibe/simvastatin and niacin (ER)
ezetimibe/simvastatin 10/20mg tablet + niacin (ER) tablet 2g, po qd. Treatment time will be \ 40 additional weeks for a total of 64 weeks
DRUGComparator: ezetimibe and simvastatin
ezetimibe/simvastatin 10/20mg tablet. Treatment time will be \ 40 additional weeks for a total of 64 weeks
DRUGComparator: Placebo to niacin (ER)
Niacin (ER) (Pbo) tablet. Treatment time will be \ 40 additional weeks for a total of 64 weeks
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Patient with LDL-C of 130 through 190 mg/dL and Triglycerides less than or equal to 500 mg/dL * Patient willing to be on a low-cholesterol diet
Exclusion criteria
* Pregnant or lactating women or intending to become pregnant * Patient with sensitivity or intolerance to ezetimibe, simvastatin, or ezetimibe/simvastatin combination tablet * Patient with sensitivity or intolerance ro niacin, any component or niacin extended release or aspirin * Patient for whom discontinuation of existing lipid-lowering therapy treatment poses an unacceptable risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | Baseline and 24 Weeks | Ezetimibe/simvastatin co-administered with niacin extended release compared to niacin extended release monotherapy on the percent change, from baseline in LDL-C after 24 weeks - 24 Week Measure Minus Baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) | Baseline and 24 weeks | Ezetimibe/simvastatin co-administered with niacin extended release compared to niacin extended release monotherapy on the percent change from baseline in non-HDL-C after 24 weeks - 24 week measure minus baseline |
| Percent Change From Baseline in High-Density Lipoprotein-Cholesterol (HDL-C) | Baseline and 24 weeks | Ezetimibe/simvastatin co-administered with niacin extended release compared to ezetimibe/simvastatin monotherapy on the percent change from baseline in HDL-C after 24 weeks - 24 week measure minus baseline |
| Percent Change From Baseline in Triglycerides (TG) | baseline and 24 Weeks | Ezetimibe/simvastatin co-administered with niacin extended release compared to ezetimibe/simvastatin monotherapy on the percent change from baseline in Triglycerides after 24 weeks - 24 week measure minus baseline |
| Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | Baseline and 64 weeks | Ezetimibe/simvastatin co-administered with niacin extended release compared to ezetimibe/simvastatin monotherapy on the percent change from baseline in LDL-C after 64 weeks - 64 week measure minus baseline |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Niacin (Part 1): Niacin titrated to 2000 mg taken orally once daily for 24 weeks. During the first 12 weeks of the study, patients randomized to the niacin containing arms started taking niacin 500 mg and had their niacin dose increased 500 mg every 4 weeks to 2000 mg. | 272 |
| Ezetimibe/Simvastatin (Part 1): Ezetimibe/Simvastatin 10/20 mg taken orally once daily for 24 weeks.
(Part 2): Ezetimibe/Simvastatin 10/20 mg taken orally once daily for 40 additional weeks for a total of 64 weeks. | 272 |
| Ezetimibe/Simvastatin + Niacin (Part 1): Ezetimibe/Simvastatin 10/20 mg + Niacin (titrated to 2000 mg as noted above) taken orally once daily for 24 weeks.
(Part 2): Ezetimibe/Simvastatin 10/20 mg + Niacin 2000 mg taken orally once daily for 40 additional weeks for a total of 64 weeks. | 676 |
| Total | 1,220 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part 1 | Adverse Event | 68 | 25 | 156 |
| Part 1 | LDL < 50 mg/dL | 1 | 4 | 48 |
| Part 1 | Lost to Follow-up | 6 | 8 | 24 |
| Part 1 | Patient Moved | 3 | 1 | 5 |
| Part 1 | Protocol Violation | 5 | 4 | 7 |
| Part 1 | Withdrawal by Subject | 23 | 17 | 45 |
| Part 2 | Adverse Event | 0 | 17 | 33 |
| Part 2 | Lack of Efficacy | 0 | 1 | 6 |
| Part 2 | LDL < 50 mg/dL | 0 | 3 | 4 |
| Part 2 | Lost to Follow-up | 0 | 6 | 18 |
| Part 2 | Patient Moved | 0 | 0 | 5 |
| Part 2 | Protocol Violation | 0 | 3 | 5 |
| Part 2 | Withdrawal by Subject | 0 | 2 | 13 |
Baseline characteristics
| Characteristic | Total | Ezetimibe/Simvastatin + Niacin | Ezetimibe/Simvastatin | Niacin |
|---|---|---|---|---|
| Age, Continuous | 56.9 years STANDARD_DEVIATION 10.7 | 56.9 years STANDARD_DEVIATION 10.9 | 57.5 years STANDARD_DEVIATION 10.3 | 56.4 years STANDARD_DEVIATION 10.6 |
| Body Mass Index <25 kg/m2 | 222 Participants | 135 Participants | 39 Participants | 48 Participants |
| Body Mass Index 25 to <30 kg/m2 | 481 Participants | 252 Participants | 119 Participants | 110 Participants |
| Body Mass Index 30 to <40 kg/m2 | 442 Participants | 251 Participants | 94 Participants | 97 Participants |
| Body Mass Index ≥ 40 kg/m2 | 69 Participants | 34 Participants | 19 Participants | 16 Participants |
| Body Mass Index No BMI Data | 6 Participants | 4 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 26 participants | 11 participants | 4 participants | 11 participants |
| Race/Ethnicity, Customized Black | 68 participants | 38 participants | 17 participants | 13 participants |
| Race/Ethnicity, Customized Hispanic | 74 participants | 49 participants | 11 participants | 14 participants |
| Race/Ethnicity, Customized Other | 5 participants | 2 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized White | 1047 participants | 576 participants | 240 participants | 231 participants |
| Sex: Female, Male Female | 608 Participants | 352 Participants | 120 Participants | 136 Participants |
| Sex: Female, Male Male | 612 Participants | 324 Participants | 152 Participants | 136 Participants |
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 | 121 / — | 428 / — | 185 / — | 175 / — | 505 / — |
| serious Total, serious adverse events | 8 / — | 13 / — | 16 / — | 29 / — | 59 / — |
Outcome results
Primary
Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C)
Ezetimibe/simvastatin co-administered with niacin extended release compared to ezetimibe/simvastatin monotherapy on the percent change from baseline in LDL-C after 24 weeks - 24 week measure minus baseline
Time frame: Baseline and 24 weeks
Population: The participant population for this analysis is the Completers Population. This includes all patients with a baseline value, who receive at least 24 weeks of active study therapy, and who have an on-treatment measurement at the maximum titrated dose per the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Niacin | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | -53.5 Percent change | Standard Error 1.2 |
| Ezetimibe/Simvastatin + Niacin | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | -58.5 Percent change | Standard Error 0.8 |
p-value: <0.00195% CI: [-7.7, -2.1]ANCOVA
Primary
Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C)
Ezetimibe/simvastatin co-administered with niacin extended release compared to niacin extended release monotherapy on the percent change, from baseline in LDL-C after 24 weeks - 24 Week Measure Minus Baseline
Time frame: Baseline and 24 Weeks
Population: The participant population for this analysis is the Completers Population. This includes all patients with a baseline value, who receive at least 24 weeks of active study therapy, and who have an on-treatment measurement at the maximum titrated dose per the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Niacin | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | -20.1 Percent change | Standard Error 1.3 |
| Ezetimibe/Simvastatin + Niacin | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | -58.5 Percent change | Standard Error 0.8 |
p-value: <0.00195% CI: [-41.4, -35.4]ANCOVA
Secondary
Percent Change From Baseline in High-Density Lipoprotein-Cholesterol (HDL-C)
Ezetimibe/simvastatin co-administered with niacin extended release compared to ezetimibe/simvastatin monotherapy on the percent change from baseline in HDL-C after 24 weeks - 24 week measure minus baseline
Time frame: Baseline and 24 weeks
Population: The participant population for this analysis is the Completers Population. This includes all patients with a baseline value, who receive at least 24 weeks of active study therapy, and who have an on-treatment measurement at the maximum titrated dose per the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Niacin | Percent Change From Baseline in High-Density Lipoprotein-Cholesterol (HDL-C) | 8.1 Percent change | Standard Error 1.3 |
| Ezetimibe/Simvastatin + Niacin | Percent Change From Baseline in High-Density Lipoprotein-Cholesterol (HDL-C) | 30.2 Percent change | Standard Error 1 |
p-value: <0.00195% CI: [18.8, 25.3]ANCOVA
Secondary
Percent Change From Baseline in High-Density Lipoprotein-Cholesterol (HDL-C)
Ezetimibe/simvastatin co-administered with niacin extended release compared to ezetimibe/simvastatin monotherapy on the percent change from baseline in HDL-C after 64 weeks - 64 week measure minus baseline
Time frame: Baseline and 64 weeks
Population: The analysis population is the modified intention-to-treat population, which includes patients that were randomized to ezetimibe/simvastatin + niacin or ezetimibe/simvastatin treatment groups and have a baseline measurement and at least on measurement beyond Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Niacin | Percent Change From Baseline in High-Density Lipoprotein-Cholesterol (HDL-C) | 9.0 Percent change | Standard Error 1.4 |
| Ezetimibe/Simvastatin + Niacin | Percent Change From Baseline in High-Density Lipoprotein-Cholesterol (HDL-C) | 30.5 Percent change | Standard Error 1.1 |
p-value: <0.00195% CI: [18, 25]ANCOVA
Secondary
Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C)
Ezetimibe/simvastatin co-administered with niacin extended release compared to ezetimibe/simvastatin monotherapy on the percent change from baseline in LDL-C after 64 weeks - 64 week measure minus baseline
Time frame: Baseline and 64 weeks
Population: The analysis population is the modified intention-to-treat population, which includes patients that were randomized to ezetimibe/simvastatin + niacin or ezetimibe/simvastatin treatment groups and have a baseline measurement and at least on measurement beyond Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Niacin | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | -49.3 Percent change | Standard Error 1.3 |
| Ezetimibe/Simvastatin + Niacin | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | -54.0 Percent change | Standard Error 1 |
p-value: 0.00495% CI: [-8, -1.5]ANCOVA
Secondary
Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C)
Ezetimibe/simvastatin co-administered with niacin extended release compared to ezetimibe/simvastatin monotherapy on the percent change from baseline in non-HDL-C after 24 weeks - 24 week measure minus baseline
Time frame: Baseline and 24 weeks
Population: The analysis population is the modified intention-to-treat population, which includes patients that were randomized to ezetimibe/simvastatin + niacin or ezetimibe/simvastatin treatment groups and have a baseline measurement and at least on measurement beyond Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Niacin | Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) | -47.9 Percent change | Standard Error 1.1 |
| Ezetimibe/Simvastatin + Niacin | Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) | -55.6 Percent change | Standard Error 0.8 |
p-value: <0.00195% CI: [-10.4, -5]ANCOVA
Secondary
Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C)
Ezetimibe/simvastatin co-administered with niacin extended release compared to niacin extended release monotherapy on the percent change from baseline in non-HDL-C after 24 weeks - 24 week measure minus baseline
Time frame: Baseline and 24 weeks
Population: The participant population for this analysis is the Completers Population. This includes all patients with a baseline value, who receive at least 24 weeks of active study therapy, and who have an on-treatment measurement at the maximum titrated dose per the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Niacin | Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) | -22.0 Percent change | Standard Error 1.3 |
| Ezetimibe/Simvastatin + Niacin | Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) | -55.6 Percent change | Standard Error 0.8 |
p-value: <0.00195% CI: [-36.5, -30.6]ANCOVA
Secondary
Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C)
Ezetimibe/simvastatin co-administered with niacin extended release compared to ezetimibe/simvastatin monotherapy on the percent change from baseline in non-HDL-C after 64 weeks - 64 week measure minus baseline
Time frame: Baseline and 64 weeks
Population: The analysis population is the modified intention-to-treat population, which includes patients that were randomized to ezetimibe/simvastatin + niacin or ezetimibe/simvastatin treatment groups and have a baseline measurement and at least on measurement beyond Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Niacin | Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) | -45.1 Percent change | Standard Error 1.3 |
| Ezetimibe/Simvastatin + Niacin | Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) | -52.4 Percent change | Standard Error 0.9 |
p-value: <0.00195% CI: [-10.4, -4.2]ANCOVA
Secondary
Percent Change From Baseline in Triglycerides (TG)
Ezetimibe/simvastatin co-administered with niacin extended release compared to ezetimibe/simvastatin monotherapy on the percent change from baseline in Triglycerides after 64 weeks - 64 week measure minus baseline
Time frame: Baseline and 64 weeks
Population: The analysis population is the modified intention-to-treat population, which includes patients that were randomized to ezetimibe/simvastatin + niacin or ezetimibe/simvastatin treatment groups and have a baseline measurement and at least on measurement beyond Week 24.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Niacin | Percent Change From Baseline in Triglycerides (TG) | -26.8 Percent change | Standard Deviation 32.7 |
| Ezetimibe/Simvastatin + Niacin | Percent Change From Baseline in Triglycerides (TG) | -44.5 Percent change | Standard Deviation 26.9 |
p-value: <0.00195% CI: [-21.8, -13.6]ANCOVA
Secondary
Percent Change From Baseline in Triglycerides (TG)
Ezetimibe/simvastatin co-administered with niacin extended release compared to ezetimibe/simvastatin monotherapy on the percent change from baseline in Triglycerides after 24 weeks - 24 week measure minus baseline
Time frame: baseline and 24 Weeks
Population: The participant population for this analysis is the Completers Population. This includes all patients with a baseline value, who receive at least 24 weeks of active study therapy, and who have an on-treatment measurement at the maximum titrated dose per the protocol.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Niacin | Percent Change From Baseline in Triglycerides (TG) | 23.7 Percent change | Standard Deviation 29.7 |
| Ezetimibe/Simvastatin + Niacin | Percent Change From Baseline in Triglycerides (TG) | -42.5 Percent change | Standard Deviation 27.5 |
p-value: <0.00195% CI: [-22.6, -14.7]ANCOVA