Hyperlipidemia, Mixed Dyslipidemia
Conditions
Brief summary
To demonstrate that niacin ER and simvastatin (NS) tablets, when compared to atorvastatin (Lipitor®; Pfizer, Inc.), has superior high-density lipoprotein cholesterol (HDL-C) elevating effects at Week 12 in subjects with type II hyperlipidemia or mixed dyslipidemia who are currently off lipid-modifying therapy. This was a prospective, randomized, open-label, blinded endpoint (PROBE) study.
Interventions
DRUGNiacin ER/Simvastatin Tablets
Up to 2000 mg/40 mg at bedtime
DRUGatorvastatin
40 mg at bedtime
Sponsors
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must meet all of the following laboratory criteria: * HDL-C \<40 mg/dL for men and \<50 mg/dL for women. * LDL-C ≥130 mg/dL but \<250 mg/dL. * TG \<350 mg/dL. * Creatine phosphokinase (CPK) \< 3 x upper limit of normal (ULN). * Alanine aminotransferase (ALT); serum glutamic pyruvic transaminase \[SGPT\] and aspartate aminotransferase (AST); serum glutamic oxaloacetic transaminase \[SGOT\] \< 1.3 x ULN. * Subjects must also be reasonably compliant with the Therapeutic Lifestyle Changes (TLC) diet during the 4 to 5 week Screening Period prior to randomization (and be willing to comply for the duration of the study).
Exclusion criteria
* Subjects who have a history of any important medical conditions or abnormalities (as specified in the protocol) that would preclude study inclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 12 | From baseline to Week 12 | (Week 12 HDL-C minus baseline HDL-C) x 100/baseline HDL-C |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in HDL-C From Baseline to Week 8 | From baseline to Week 8 | (Week 8 HDL-C minus baseline HDL-C) x 100/baseline HDL-C |
| Percent Change in Non-HDL-C From Baseline to Week 8 | From baseline to Week 8 | (Week 8 non-HDL-C minus baseline non-HDL-C) x 100/baseline non-HDL-C |
| Percent Change in Non-HDL-C From Baseline to Week 12 | From baseline to Week 12 | (Week 12 non-HDL-C minus baseline non-HDL-C) x 100/baseline non-HDL-C |
| Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 | From baseline to Week 12 | (Week 12 LDL-C minus baseline LDL-C) x 100/baseline LDL-C |
| Percent Change in Triglycerides From Baseline to Week 12 | From baseline to Week 12 | (Week 12 triglycerides minus baseline triglycerides) x 100/baseline triglycerides |
| Percent Change in LDL-C:HDL-C Ratio | From baseline to Week 12 | (Week 12 LDL-C:HDL-C ratio minus baseline LDL-C:HDL-C ratio) x 100/baseline LDL-C:HDL-C ratio |
| Percentage of Subjects Meeting With HDL-C >/= 40 mg/dL at Week 12 | 12 weeks | — |
| Percent Change in Total Cholesterol:HDL-C Ratio | From baseline to Week 12 | (Week 12 total cholesterol:HDL-C ratio minus baseline total cholesterol:HDL-C ratio) x 100/baseline total cholesterol:HDL-C ratio |
| Percent Change in Lipoprotein A From Baseline to Week 12 | From baseline to Week 12 | (Week 12 lipoprotein A minus baseline lipoprotein A) x 100/baseline lipoprotein A |
| Percentage of Subjects Meeting National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III Goal for LDL-C at Week 12 | 12 weeks | For high-risk patients (coronary heart disease or equivalent), LDL-C \< 100 mg/dL and non-HDL-C \< 130 mg/dL; for moderate risk patients (having 2 risk factors), LDL-C \< 130 mg/dL and non-HDL-C \< 160 mg/dL; for low-risk patients (having 0 or 1 risk factor): LDL-C \< 160 mg/dL and non-HDL-C \< 190 mg/dL. |
| Percentage of Subjects With Triglycerides < 150 mg/dL at Week 12 | 12 weeks | — |
| Percentage of Subjects With HDL-C >/= 40 mg/dL, LDL-C Meeting NCEP ATP III Goal, and Triglycerides < 150 mg/dL at Week 12 | 12 weeks | NCEP ATP III goals for LDL-C are as follows: For high-risk patients, LDL-C \< 100 mg/dL; for moderate risk patients, LDL-C \< 130 mg/dL; for low-risk patients: LDL-C \< 160 mg/dL. High-risk means coronary heart disease or risk equivalents; moderate risk means having at least 2 risk factors; low-risk means having no or 1 risk factor. |
| Percent Change in Total Cholesterol From Baseline to Week 12 | From baseline to Week 12 | (Week 12 total cholesterol minus baseline total cholesterol) x 100/baseline total cholesterol |
Countries
United States
Participant flow
Pre-assignment details
Of the 199 subjects randomized, 6 did not receive study drug: 2 withdrew consent, 1 had a protocol violation, and 3 had randomization errors. 193 subjects were treated.
Participants by arm
| Arm | Count |
|---|---|
| Niacin Extended-release Plus Simvastatin Up to 2000 mg of niacin extended-release plus 40 mg simvastatin once daily at bedtime | 114 |
| Atorvastatin 40 mg atorvastatin once daily at bedtime | 79 |
| Total | 193 |
Baseline characteristics
| Characteristic | Atorvastatin | Niacin Extended-release Plus Simvastatin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 21 Participants | 27 Participants |
| Age, Categorical Between 18 and 65 years | 73 Participants | 93 Participants | 166 Participants |
| Age Continuous | 51.5 years STANDARD_DEVIATION 11.12 | 55.1 years STANDARD_DEVIATION 12.06 | 53.6 years STANDARD_DEVIATION 11.8 |
| Region of Enrollment United States | 79 participants | 114 participants | 193 participants |
| Sex: Female, Male Female | 38 Participants | 71 Participants | 109 Participants |
| Sex: Female, Male Male | 41 Participants | 43 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 89 / — | 27 / — |
| serious Total, serious adverse events | 2 / — | 1 / — |
Outcome results
Primary
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 12
(Week 12 HDL-C minus baseline HDL-C) x 100/baseline HDL-C
Time frame: From baseline to Week 12
Population: All treated subjects whose Week 12 value was obtained within the Week 12 visit window
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 12 | 30.1 percent change |
| Atorvastatin | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 12 | 9.4 percent change |
Comparison: An n = 81 for niacin extended-release with simvastatin and n = 54 for atorvastatin would provide \> 99% power to detect a 13% increase in HDL-C with niacin extended-release with simvastatin relative to atorvastatin, assuming an SD of 16%p-value: <0.001Mixed Models Analysis
Secondary
Percentage of Subjects Meeting National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III Goal for LDL-C at Week 12
For high-risk patients (coronary heart disease or equivalent), LDL-C \< 100 mg/dL and non-HDL-C \< 130 mg/dL; for moderate risk patients (having 2 risk factors), LDL-C \< 130 mg/dL and non-HDL-C \< 160 mg/dL; for low-risk patients (having 0 or 1 risk factor): LDL-C \< 160 mg/dL and non-HDL-C \< 190 mg/dL.
Time frame: 12 weeks
Population: All treated subjects not meeting NCEP ATP III goals at baseline with both a baseline and at least 1 postbaseline LDL-C value
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percentage of Subjects Meeting National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III Goal for LDL-C at Week 12 | 78 Percentage of subjects |
| Atorvastatin | Percentage of Subjects Meeting National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III Goal for LDL-C at Week 12 | 84 Percentage of subjects |
Secondary
Percentage of Subjects Meeting With HDL-C >/= 40 mg/dL at Week 12
Time frame: 12 weeks
Population: All treated subjects not meeting National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III goals at baseline with both a baseline and at least 1 postbaseline HDL-C value
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percentage of Subjects Meeting With HDL-C >/= 40 mg/dL at Week 12 | 78 Percentage of subjects |
| Atorvastatin | Percentage of Subjects Meeting With HDL-C >/= 40 mg/dL at Week 12 | 28 Percentage of subjects |
Secondary
Percentage of Subjects With HDL-C >/= 40 mg/dL, LDL-C Meeting NCEP ATP III Goal, and Triglycerides < 150 mg/dL at Week 12
NCEP ATP III goals for LDL-C are as follows: For high-risk patients, LDL-C \< 100 mg/dL; for moderate risk patients, LDL-C \< 130 mg/dL; for low-risk patients: LDL-C \< 160 mg/dL. High-risk means coronary heart disease or risk equivalents; moderate risk means having at least 2 risk factors; low-risk means having no or 1 risk factor.
Time frame: 12 weeks
Population: All treated subjects not meeting NCEP ATP III goals at baseline with both a baseline and at least 1 postbaseline value for all 3 lipid parameters
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percentage of Subjects With HDL-C >/= 40 mg/dL, LDL-C Meeting NCEP ATP III Goal, and Triglycerides < 150 mg/dL at Week 12 | 65 Percentage of subjects |
| Atorvastatin | Percentage of Subjects With HDL-C >/= 40 mg/dL, LDL-C Meeting NCEP ATP III Goal, and Triglycerides < 150 mg/dL at Week 12 | 34 Percentage of subjects |
Secondary
Percentage of Subjects With Triglycerides < 150 mg/dL at Week 12
Time frame: 12 weeks
Population: All treated subjects not meeting NCEP ATP III goals at baseline with both a baseline and at least 1 postbaseline triglyceride value
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percentage of Subjects With Triglycerides < 150 mg/dL at Week 12 | 79 Percentage of subjects |
| Atorvastatin | Percentage of Subjects With Triglycerides < 150 mg/dL at Week 12 | 70 Percentage of subjects |
Secondary
Percent Change in HDL-C From Baseline to Week 8
(Week 8 HDL-C minus baseline HDL-C) x 100/baseline HDL-C
Time frame: From baseline to Week 8
Population: All treated subjects whose Week 8 value was obtained within the Week 8 visit window
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percent Change in HDL-C From Baseline to Week 8 | 26.7 percent change |
| Atorvastatin | Percent Change in HDL-C From Baseline to Week 8 | 1.4 percent change |
Secondary
Percent Change in LDL-C:HDL-C Ratio
(Week 12 LDL-C:HDL-C ratio minus baseline LDL-C:HDL-C ratio) x 100/baseline LDL-C:HDL-C ratio
Time frame: From baseline to Week 12
Population: All treated subjects whose Week 12 values were obtained within the Week 12 visit window
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percent Change in LDL-C:HDL-C Ratio | -54.5 percent change |
| Atorvastatin | Percent Change in LDL-C:HDL-C Ratio | -50.5 percent change |
Secondary
Percent Change in Lipoprotein A From Baseline to Week 12
(Week 12 lipoprotein A minus baseline lipoprotein A) x 100/baseline lipoprotein A
Time frame: From baseline to Week 12
Population: All treated subjects whose Week 12 value was obtained within the Week 12 visit window
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percent Change in Lipoprotein A From Baseline to Week 12 | -15.8 percent change |
| Atorvastatin | Percent Change in Lipoprotein A From Baseline to Week 12 | 16.0 percent change |
Secondary
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12
(Week 12 LDL-C minus baseline LDL-C) x 100/baseline LDL-C
Time frame: From baseline to Week 12
Population: All treated subjects whose Week 12 value was obtained within the Week 12 visit window (between 70 days after first dose and not more than 3 days after last dose)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 | -43.8 percent change |
| Atorvastatin | Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 | -46.0 percent change |
Secondary
Percent Change in Non-HDL-C From Baseline to Week 12
(Week 12 non-HDL-C minus baseline non-HDL-C) x 100/baseline non-HDL-C
Time frame: From baseline to Week 12
Population: All treated subjects whose Week 12 value was obtained within the Week 12 visit window
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percent Change in Non-HDL-C From Baseline to Week 12 | -43.4 percent change |
| Atorvastatin | Percent Change in Non-HDL-C From Baseline to Week 12 | -43.3 percent change |
Secondary
Percent Change in Non-HDL-C From Baseline to Week 8
(Week 8 non-HDL-C minus baseline non-HDL-C) x 100/baseline non-HDL-C
Time frame: From baseline to Week 8
Population: All treated subjects whose Week 8 value was obtained within the Week 8 visit window
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percent Change in Non-HDL-C From Baseline to Week 8 | -45.0 percent change |
| Atorvastatin | Percent Change in Non-HDL-C From Baseline to Week 8 | -44.3 percent change |
Secondary
Percent Change in Total Cholesterol From Baseline to Week 12
(Week 12 total cholesterol minus baseline total cholesterol) x 100/baseline total cholesterol
Time frame: From baseline to Week 12
Population: All treated subjects whose Week 12 value was obtained within the Week 12 visit window
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percent Change in Total Cholesterol From Baseline to Week 12 | -31.3 percent change |
| Atorvastatin | Percent Change in Total Cholesterol From Baseline to Week 12 | -35.1 percent change |
Secondary
Percent Change in Total Cholesterol:HDL-C Ratio
(Week 12 total cholesterol:HDL-C ratio minus baseline total cholesterol:HDL-C ratio) x 100/baseline total cholesterol:HDL-C ratio
Time frame: From baseline to Week 12
Population: All treated subjects whose Week 12 values were obtained within the Week 12 visit window
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percent Change in Total Cholesterol:HDL-C Ratio | -45.2 percent change |
| Atorvastatin | Percent Change in Total Cholesterol:HDL-C Ratio | -40.3 percent change |
Secondary
Percent Change in Triglycerides From Baseline to Week 12
(Week 12 triglycerides minus baseline triglycerides) x 100/baseline triglycerides
Time frame: From baseline to Week 12
Population: All treated subjects whose Week 12 value was obtained within the Week 12 visit window
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Niacin Extended-release Plus Simvastatin | Percent Change in Triglycerides From Baseline to Week 12 | -44.0 percent change |
| Atorvastatin | Percent Change in Triglycerides From Baseline to Week 12 | -37.0 percent change |