Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Comparator: simvastatin
Simvastatin · 6 trials · 9 indications
Blood samples taken at baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment during each period to determine the LDL-C levels. The change from baseline after 8 weeks of treatment was recorded.
Non-fatal myocardial infarction or coronary death, non-fatal or fatal stroke, or revascularisation
Excised carotid plaques were evaluated for the gene expression of 60 biomarkers associated with inflammation ("Hot" biomarkers) \& 25 biomarkers associated with stability ("Cold" biomarkers). Each biomarker was assayed using a quantitative polymerase chain reaction method and results were reported as a Cycle Threshold, (Ct). A Composite Score was calculated by averaging the Ct for each of the 25 "cold" genes, and subtracting the average Ct for the 60 "hot" genes. A higher composite score was associated with greater inflammation and a lower score was associated with stability (non-inflamed).
Each excised plaque was analyzed using an assay of 20 proteins that reflect plaque composition and inflammation. Each protein was assigned scaled signs, with a lower (negative) sign associated with plaque stability and a higher (positive) sign associated with plaque inflammation/instability. The Composite Score was the average amounts of all the 20 proteins with their associated signs. A higher Composite Score is associated with more plaque instability.
Cholesterol ester was to be calculated by the following formula: Cholesterol Ester = Total Cholesterol - Free Cholesterol.
Arachidonic acid level (20:4n6) in the cholesterol ester lipid class. The mean reported was an adjusted mean, which was obtained from running a 2-period crossover model that had fixed treatment and period terms and a random participant term.
| Arm | Type | Description |
|---|---|---|
| 1 | OTHER | 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. |
| 2 | ACTIVE_COMPARATOR | Stable dose of simvastatin or atorvastatin (20mg to 40mg) for 12 weeks. |
| Sequence 1: MK-0524B 1.8g/20mg→MK-0524A 2g+Simvastatin 20mg | EXPERIMENTAL | After a 2-week placebo run-in, participants will receive MK-0524B (0.9 g/simvastatin 10 mg) for 4 weeks, then MK-0524B 1.8g /20 mg combination tablet for 8 weeks. Participant is then co-administered MK-0524A 2 g + simvastatin 20 mg for 8 weeks. |
| Sequence 2: MK-0524A 2g+Simvastatin 20mg →MK-0524B 1.8g/20mg | EXPERIMENTAL | After a 2-week placebo run-in, participants will be co-administered MK-0524A 1g + simvastatin 10 mg for 4 weeks, then co-administered MK-0524A 2g +simvastatin 20 mg for 8 weeks. Participant then receives MK-0524B 1.8 g/20 mg combination tablet for 8 weeks. |
| Sequence 3: MK-0524B 1.8g/40mg→MK-0524A 2g+Simvastatin 40mg | EXPERIMENTAL | After a 2-week placebo run-in, participants will receive MK-0524B 0.9g/40 mg combination tablet for 4 weeks, then MK-0524B 1.8g /40 mg combination tablet for 8 weeks. Participant is then co-administered MK-0524A 2 g + simvastatin 40 mg for 8 weeks. |
| Sequence 4: MK-0524A 2g+Simvastatin 40mg →MK-0524B 1.8g/40mg | EXPERIMENTAL | After a 2-week placebo run-in, participants will be co-administered MK-0524A 1g + simvastatin 40 mg for 4 weeks, then co-administration MK-0524A 2g +simvastatin 40 mg for 8 weeks. Participant then receives MK-0524B 1.8 g/40 mg combination tablet for 8 weeks. |
| ER niacin/laropiprant | EXPERIMENTAL | 1 g ER niacin plus 20 mg laropiprant per tablet. 2 tablets orally per day. With either 40 mg simvastatin tablet or ezetimibe/simvastatin (10 mg/40 mg) in single tablet taken once daily |
| Placebo | ACTIVE_COMPARATOR | Placebo (for ER niacin/laropiprant) 2 tablets orally per day. With either 40 mg simvastatin tablet orally per day or ezetimibe/simvastatin (10 mg/40 mg) in single tablet taken once daily |
| Statin 80 mg + Niacin extended-release (ER) | EXPERIMENTAL | Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will receive 80 mg Atorvastatin + niacin. |
| Statin 10 mg | ACTIVE_COMPARATOR | Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin. |
| Simvastatin 40 mg first, then placebo | EXPERIMENTAL | Simvastatin 40 mg tablets once daily for 2 weeks followed by placebo for 2 weeks |
| Placebo first, then simvastatin 40 mg once daily | PLACEBO_COMPARATOR | Placebo for 2 weeks followed by simvastatin 40 mg once daily for 2 weeks |
| Name | Type | Description |
|---|---|---|
| Comparator: simvastatin | DRUG | simvastatin (20mg to 40mg) for 12 weeks. |
| niacin (+) laropiprant | DRUG | 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. |
| Comparator: atorvastatin calcium | DRUG | atorvastatin calcium (20mg to 40mg) for 12 weeks. |
| MK-0524A | DRUG | Extended-release(ER) niacin/Laropiprant (MK-0524) Combination tablet |
| Placebo | DRUG | - |
| MK-0524B | DRUG | - |
| ER niacin/laropiprant | DRUG | - |
| simvastatin | DRUG | 40 mg simvastatin tablet orally per day as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level |
| ezetimibe/simvastatin | DRUG | 10 mg ezetimibe plus 40 mg simvastatin in single tablet taken once daily as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level |
| Atorvastatin/niacin extended-release | DRUG | 80 mg tablet atorvastatin once daily, 10 mg tablet placebo to atorvastatin once daily, and niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks. |
| Atorvastatin | DRUG | 10 mg tablet atorvastatin once daily, 80 mg tablet placebo to atorvastatin once daily, and placebo to niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks. |
| simvastatin 20 mg/ezetimibe | DRUG | see protocol |
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 w...