Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Zocor
Simvastatin · 7 trials · 10 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...
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| United Therapeutics Corporation | UTHR | 1 | PHASE3 | Ralinepag |
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| Eli Lilly and Company | LLY | 1 | PHASE3 | Lepodisiran |
| Illumina, Inc. | ILMN | 1 | PHASE1 | 18F-mFBG for administration |
Simvastatin is used to treat lipid disorders including hypercholesterolemia, dyslipidemia, hyperlipidemia, and primary hypercholesterolemia. It is also being studied in cardiovascular conditions such as atrial fibrillation, cardiovascular disease, and carotid atherosclerosis. It is a small molecule developed by Merck & Company, Inc.
Simvastatin targets HMGCR, also known as HMG-CoA reductase. It acts as an inhibitor of this enzyme, which is involved in cholesterol synthesis. By inhibiting HMGCR, simvastatin reduces cholesterol production in the body.
Simvastatin is developed by Merck & Company, Inc., which trades under the ticker MRK. Merck is the sponsor of the clinical trials evaluating simvastatin in cardiovascular and lipid disorders.
Simvastatin has been studied in Phase 1, Phase 2, and Phase 3 clinical trials. The highest phase reported is Phase 3. It is an investigational product in the trials listed and has been evaluated in completed studies.
Simvastatin has been evaluated in completed trials including NCT00935259, a Phase 1 lipid biomarker study in men with dyslipidemia; NCT00804843, a Phase 2 carotid atherosclerosis trial; NCT00566267, a Phase 2 study in hyperlipidemia; and NCT00479882, a Phase 3 lipid study in primary hypercholesterolemia and mixed dyslipidemia.