Primary Hypercholesterolemia, Mixed Dyslipidemia
Conditions
Brief summary
This is a 12-Week clinical trial in patients with Primary hypercholesterolemia or mixed dyslipidemia to study the effects of ER niacin/laropiprant on lipids.
Interventions
simvastatin (20mg to 40mg) for 12 weeks.
One tablet of ER niacin/ laropiprant (1g); titrating up to ER niacin/laropiprant (2g) at Week 4 for an additional 8 weeks, with no adjustments to the run-in statin dose.
atorvastatin calcium (20mg to 40mg) for 12 weeks.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients 18 to 80 years of age with Primary hypercholesterolemia or mixed dyslipidemia * Patients will be eligible for the study if their LDL-C values are within protocol specified range and meet other entry criteria
Exclusion criteria
* Patient whose LDL-C values are not within protocol specified range
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12 | Baseline and 12 Weeks |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12 | Baseline and 12 Weeks |
| Percent Change From Baseline in Triglycerides at Week 12 | Baseline and 12 Weeks |
Participant flow
Recruitment details
First Patient In: 30-Jul-2007 Last Patient Last Visit: 10-Jul-2008 Investigators: 161 sites participated: Australia-5; Austria-4; Canada-11; Czech Republic-5; Denmark-4; France-10; Germany-24; Hungary-6; Israel-4; Italy-11; Netherlands-2; Norway-10; Poland-11; Russian Federation-7; South Africa-9; Spain-4; Sweden-17; United States-17
Pre-assignment details
Patients on atorvastatin (10mg) or simvastatin (10mg or 20mg) had a 2 week run-in of their statin. Naïve patients or patients on other statins were started on simvastatin (10 or 20mg) or atorvastatin (10mg) for a 6 week run-in. Patients were eligible to be randomized if their Visit 1 low density lipoprotein cholesterol values were above goal.
Participants by arm
| Arm | Count |
|---|---|
| ER Niacin/Laropiprant + Run-in Statin One tablet of ER niacin/ laropiprant (1g) + one tablet of the run-in statin dose, titrating up to ER niacin/laropiprant (2g) at Week 4 for an additional 8 weeks, with no adjustments to the run-in statin dose. | 606 |
| Run-in Statin Dose Doubled Stable dose of simvastatin or atorvastatin (20mg to 40mg) for 12 weeks. | 610 |
| Total | 1,216 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 90 | 45 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Protocol Violation | 10 | 9 |
| Overall Study | Withdrawal by Subject | 32 | 17 |
Baseline characteristics
| Characteristic | ER Niacin/Laropiprant + Run-in Statin | Run-in Statin Dose Doubled | Total |
|---|---|---|---|
| Age, Continuous | 60.4 years STANDARD_DEVIATION 9.7 | 60.6 years STANDARD_DEVIATION 9.8 | 60.5 years STANDARD_DEVIATION 9.7 |
| Coronary Heart Disease Risk Category by Goal High Risk at Goal | 143 Participants | 155 Participants | 298 Participants |
| Coronary Heart Disease Risk Category by Goal High Risk Not at Goal | 237 Participants | 262 Participants | 499 Participants |
| Coronary Heart Disease Risk Category by Goal Low Risk at Goal | 27 Participants | 26 Participants | 53 Participants |
| Coronary Heart Disease Risk Category by Goal Low Risk Not at Goal | 16 Participants | 14 Participants | 30 Participants |
| Coronary Heart Disease Risk Category by Goal Multiple Risk at Goal | 91 Participants | 82 Participants | 173 Participants |
| Coronary Heart Disease Risk Category by Goal Multiple Risk Not at Goal | 92 Participants | 71 Participants | 163 Participants |
| Fasting Serum Glucose (FSG) | 108.3 mg/dL STANDARD_DEVIATION 27.2 | 108.7 mg/dL STANDARD_DEVIATION 27.7 | 108.5 mg/dL STANDARD_DEVIATION 27.4 |
| High-density lipoprotein cholesterol | 54.89 mg/dL STANDARD_DEVIATION 14.45 | 54.97 mg/dL STANDARD_DEVIATION 13.91 | 54.93 mg/dL STANDARD_DEVIATION 14.17 |
| Lipid Modification Type/Dose at Run-in Atorvastatin 10 mg | 129 participants | 109 participants | 238 participants |
| Lipid Modification Type/Dose at Run-in Simvastatin 10 mg | 218 participants | 233 participants | 451 participants |
| Lipid Modification Type/Dose at Run-in Simvastatin 20 mg | 259 participants | 268 participants | 527 participants |
| Low-density lipoprotein cholesterol | 117.55 mg/dL STANDARD_DEVIATION 28.66 | 115.82 mg/dL STANDARD_DEVIATION 28.37 | 116.68 mg/dL STANDARD_DEVIATION 28.52 |
| Sex: Female, Male Female | 304 Participants | 289 Participants | 593 Participants |
| Sex: Female, Male Male | 302 Participants | 321 Participants | 623 Participants |
| Triglycerides (TG) | 136.00 mg/dL | 124.00 mg/dL | 130.00 mg/dL |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 249 / — | 172 / — |
| serious Total, serious adverse events | 14 / — | 8 / — |
Outcome results
Primary
Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12
Time frame: Baseline and 12 Weeks
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ER Niacin/Laropiprant + Run-in Statin | Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12 | -10.0 Percent |
| Run-in Statin Dose Doubled | Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12 | -5.5 Percent |
p-value: 0.00695% CI: [-7.7, -1.3]Repeated measures analysis
Secondary
Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12
Time frame: Baseline and 12 Weeks
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ER Niacin/Laropiprant + Run-in Statin | Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12 | 15.8 Percent |
| Run-in Statin Dose Doubled | Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12 | 0.2 Percent |
p-value: <=0.00195% CI: [13.4, 17.9]Repeated measures analysis
Secondary
Percent Change From Baseline in Triglycerides at Week 12
Time frame: Baseline and 12 Weeks
Population: Full Analysis Set With at Least one Post-Titration Visit Measurement
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ER Niacin/Laropiprant + Run-in Statin | Percent Change From Baseline in Triglycerides at Week 12 | -17.6 Percent |
| Run-in Statin Dose Doubled | Percent Change From Baseline in Triglycerides at Week 12 | -4.0 Percent |
p-value: <=0.00195% CI: [-19.2, -11.7]Repeated measures analysis