Hypercholesterolemia, Hyperlipidemia
Conditions
Keywords
High Cholesterol, Excess lipids
Brief summary
The primary objective of the study is to assess the effects of MK0524A in reducing cholesterol levels in an Asian population.
Interventions
DRUGlaropiprant/niacin (MK0524A)
Treatment Period 1: one 20mg/1g tablet laropiprant/niacin once daily for 4 weeks Treatment Period 2: two 20mg/1g tablets laropiprant/niacin once daily for 8 weeks. All patients will receive placebo for a 4 week run-in period before randomization
DRUGComparator: placebo
Treatment Period 1: one 20mg/1g tablet placebo to laropiprant/niacin once daily for 4 weeks Treatment Period 2: two 20mg/1g tablets of placebo to laropiprant/niacin once daily for 8 weeks. All patients will receive placebo for a 4 week run-in period before randomization.
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 70 Years
Healthy volunteers
No
Inclusion criteria
* Patient is male or female between 18 and 70 years of age * Females of reproductive potential must agree to take acceptable contraceptive precautions for the duration of the study
Exclusion criteria
* Patient has a history of not being able to take niacin or niacin-containing products * Patient consumes more than 2 alcoholic beverages per day * Patient has poorly controlled Type 1 or Type 2 diabetes mellitus * Patient engages in vigorous exercise or an aggressive diet regimen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) After 12 Weeks | 12 weeks | Low Density Lipoprotein Cholesterol (LDL-C) after 12 weeks is calculated as the difference between week 12 measure and baseline measure divided by baseline measure \*100 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) After 12 Weeks | 12 weeks | Percent change from baseline in High Density Lipoprotein Cholesterol (HDL-C) after 12 weeks is calculated as the difference between week 12 measure and baseline measure divided by baseline measure \*100 |
Participant flow
Recruitment details
Phase III First Patient In: 10-May-2007 Last Patient Last Visit: 11-Mar-2008 42 Outpatient centers in China (21), Hong Kong (2), India (11), and Korea (8)
Pre-assignment details
Asia-regional lipid study with patients 18-70 yrs, including diabetic patients +/- statin, without ischemic vascular disease and LDL-C\<130 mg/dL (3.37 mmol/L), patients on a statin with ≥2 risk factors with LDL-C ≥130 and ≤160 mg/dL (3.37 and 4.14 mmol/L), and patients +/- statin with ≤1 risk factor with ≥130 and ≤190 mg/dL (3.37 and 4.92 mmol/L).
Participants by arm
| Arm | Count |
|---|---|
| MK0524A 2 g All patients received placebo for a 4 week run-in period before randomization.
Drug: laropiprant/niacin (MK0524A)
Treatment Period 1: one 20 mg /1 g tablet of laropiprant/niacin once daily for 4 weeks.
Treatment Period 2: two 20 mg /1 g tablets of laropiprant/niacin once daily for 8 weeks. | 322 |
| Placebo All patients received placebo for a 4 week run-in period before randomization.
Drug: Comparator: placebo
Treatment Period 1: one 20 mg /1 g tablet placebo to laropiprant/niacin once daily for 4 weeks
Treatment Period 2: two 20 mg /1 g tablets of placebo to laropiprant/niacin once daily for 8 weeks. | 324 |
| Total | 646 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 27 | 4 |
| Overall Study | Flushing with Product | 20 | 0 |
| Overall Study | Laboratory Adverse Event | 2 | 1 |
| Overall Study | Lost to Follow-up | 11 | 8 |
| Overall Study | Patient Discontinued for Other Reasons | 2 | 2 |
| Overall Study | Protocol Violation | 4 | 5 |
| Overall Study | Withdrawal by Subject | 16 | 9 |
Baseline characteristics
| Characteristic | Placebo | Total | MK0524A 2 g |
|---|---|---|---|
| Age, Customized <65 years | 279 participants | 555 participants | 276 participants |
| Age, Customized >=65 years | 45 participants | 91 participants | 46 participants |
| Concomitant Statin Use No | 178 Participants | 350 Participants | 172 Participants |
| Concomitant Statin Use Yes | 146 Participants | 296 Participants | 150 Participants |
| Country China (includes Hong Kong) | 158 Participants | 317 Participants | 159 Participants |
| Country India | 79 Participants | 161 Participants | 82 Participants |
| Country Korea | 87 Participants | 168 Participants | 81 Participants |
| Glycemic Status Diabetic* | 164 Participants | 312 Participants | 148 Participants |
| Glycemic Status Impaired Glucose* | 4 Participants | 12 Participants | 8 Participants |
| Glycemic Status Normal* | 156 Participants | 322 Participants | 166 Participants |
| High Density Lipoprotein Cholesterol (HDL-C) | 48.5 mg/dL STANDARD_DEVIATION 11.8 | 48.3 mg/dL STANDARD_DEVIATION 11.3 | 48.1 mg/dL STANDARD_DEVIATION 10.8 |
| Low Density Lipoprotein Cholesterol (LDL-C) | 121.8 mg/dL STANDARD_DEVIATION 34 | 122.9 mg/dL STANDARD_DEVIATION 34.2 | 124 mg/dL STANDARD_DEVIATION 34.4 |
| Sex: Female, Male Female | 185 Participants | 376 Participants | 191 Participants |
| Sex: Female, Male Male | 139 Participants | 270 Participants | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 123 / 321 | 54 / 323 |
| serious Total, serious adverse events | 3 / 321 | 2 / 323 |
Outcome results
Primary
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) After 12 Weeks
Low Density Lipoprotein Cholesterol (LDL-C) after 12 weeks is calculated as the difference between week 12 measure and baseline measure divided by baseline measure \*100
Time frame: 12 weeks
Population: Full Analysis Set: consisted of all randomized patients who (i) took at least one dose of the treatment period study medication and (ii) had a baseline measurement and at least one measurement during Weeks 5 to 12. The last available lipid values during Weeks 5 to 12 were used for patients who had no lipid data collected at Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK0524A 2 g | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) After 12 Weeks | -10.3 Percent Change |
| Placebo | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) After 12 Weeks | 4.4 Percent Change |
Comparison: The primary hypothesis of superiority of MK0524A 2 g to placebo in lowering Low Density Lipoprotein Cholesterol (LDL-C) was assessed using the comparison between these 2 groups from the ANOVA model.p-value: <0.00195% CI: [-18.6, -10.9]ANOVA
Secondary
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) After 12 Weeks
Percent change from baseline in High Density Lipoprotein Cholesterol (HDL-C) after 12 weeks is calculated as the difference between week 12 measure and baseline measure divided by baseline measure \*100
Time frame: 12 weeks
Population: Full Analysis Set: consisted of all randomized patients who (i) took at least one dose of the treatment period study medication and (ii) had a baseline measurement and at least one measurement during Weeks 5 to 12. The last available lipid values during Weeks 5 to 12 were used for patients who had no lipid data collected at Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK0524A 2 g | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) After 12 Weeks | 18.6 Percent Change |
| Placebo | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) After 12 Weeks | 2.6 Percent Change |
Comparison: The secondary hypothesis of superiority of MK0524A 2 g to placebo in lowering High Density Lipoprotein Cholesterol (HDL-C) was assessed using the comparison between these 2 groups from the ANOVA model.p-value: <0.00195% CI: [12.6, 19.2]ANOVA