Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance

BackgroundOnce-daily, oral ETC-1002 reduces low-density lipoprotein cholesterol (LDL-C) and has beneficial effects on other cardiometabolic risk factors but has not been examined in statin intolerant patients.ObjectivesTo study the efficacy and safety of ETC-1002 (a novel LDL-C–lowering agent) in patients with hypercholesterolemia and a history of statin intolerance.MethodsPatients intolerant to at least 1 statin were entered into this multicenter, double-blind, 8-week trial. Participants were required to have a history of muscle complaints that developed during statin treatment and resolved within 4 weeks of statin discontinuation. Patients (n = 56) were randomized in a 2:1 ratio to ETC-1002 60 mg daily or placebo. The ETC-1002 dose was increased at 2-week intervals to 120 mg, 180 mg, and 240 mg. The primary end point was the percentage change from baseline to week 8 in calculated LDL-C.ResultsETC-1002 reduced LDL-C 28.7% more than placebo (95% confidence interval, −35.4 to −22.1; P < .0001). ETC-1002 significantly reduced non–high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. Triglycerides and high-density lipoprotein cholesterol did not change with ETC-1002 treatment. Sixty-two percent of patients receiving ETC-1002 and none in the placebo group achieved the 2004 National Cholesterol Education Program Adult Treatment Panel III LDL-C goal (P < .0001). Muscle-related adverse events occurred with similar frequency in the placebo and ETC-1002 treatment groups, causing no discontinuations in ETC-1002–treated patients.ConclusionsETC-1002 appears to be effective at reducing LDL-C and was well tolerated in patients with statin-associated muscle complaints. Longer and larger studies are required to confirm the absence of muscle side effects

Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance

BackgroundETC-1002 is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia.ObjectivesTo compare 2 doses of ETC-1002, alone or combined with ezetimibe 10 mg (EZE), vs EZE monotherapy for lowering low-density lipoprotein cholesterol (LDL-C).MethodsThis phase 2b, multicenter, double-blind trial-evaluated hypercholesterolemic patients (LDL-C, 130 to 220 mg/dL) with (n = 177) or without (n = 171) muscle-related intolerance to ≥2 statins; 1 at lowest approved dose. Subjects were randomized to 12-week treatment with ETC-1002 120 mg or ETC-1002 180 mg alone, EZE alone, ETC-1002 120 mg plus EZE, or ETC-1002 180 mg plus EZE.ResultsEZE alone lowered LDL-C by 21%, whereas ETC-1002 monotherapy with 120 mg or 180 mg reduced LDL-C by 27% (P = .0008 vs EZE) and 30% (P < .0001 vs EZE), respectively. The combination of ETC-1002, 120 mg or 180 mg plus EZE reduced LDL-C by 43% and 48%, respectively (both P < .0001 vs EZE). ETC-1002 alone or combined with EZE also reduced non–high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, LDL particle number, and high-sensitivity C-reactive protein compared with EZE alone. Across all treatment groups, statin-intolerant patients reported more muscle-related adverse events than did statin-tolerant patients. ETC-1002 was safe and well tolerated, and rates of muscle-related adverse events were similar in all treatment groups.ConclusionsIn patients with and without statin intolerance, daily treatment with ETC-1002 120 mg and 180 mg alone or with EZE reduced LDL-C more than EZE alone and had a similar tolerability profile (NCT01941836)

Efficacy and safety of bempedoic acid in patients not receiving statins in phase 3 clinical trials

BACKGROUND: Despite the high incidence of patients with statin tolerance problems, randomized evaluations of nonstatin oral treatment options for lowering of low-density lipoprotein cholesterol (LDL-C) in this population are sparse. OBJECTIVE: To assess the LDL-C lowering effect of bempedoic acid in patients not taking statins. METHODS: This was a pooled analysis of data from patients enrolled in four phase 3 bempedoic acid studies (12 to 52 weeks in duration) who were not taking concomitant statins (Phase 3 No Statin Cohort) and a phase 3 bempedoic acid plus ezetimibe fixed-dose combination study (BA+EZE FDC No Statin Cohort). The primary endpoint for all studies was the percent change from baseline to week 12 in LDL-C levels. Safety and tolerability were assessed by laboratory values and adverse events. RESULTS: In the Phase 3 No Statin Cohort, bempedoic acid (n = 394) lowered LDL-C levels at week 12 significantly more than placebo (n = 192; -26.5% [95% CI, -29.7%, -23.2%]; P\u3c0.001). The fixed-dose combination of bempedoic acid with ezetimibe lowered LDL-C by 39.2% (95% CI, -51.7% to -26.7%; P\u3c0.001). Muscle-related disorders occurred at a rate of 26.4 and 28.6 per 100 person-years with bempedoic acid and placebo, respectively. CONCLUSIONS: In patients with hypercholesterolemia unable to take statins, bempedoic acid lowered LDL-C levels by a mean of 26.5% vs placebo and bempedoic acid + ezetimibe fixed-dose combination lowered LDL-C by 39.2%. The treatments were generally well tolerated, suggesting that bempedoic acid may be efficacious and well tolerated in this challenging-to-treat patient population

The oxidation of fatty acids and other substrates in healthy men fed butterfat versus beef tallow

To assess the influence of dietary fat composition on postprandial oxidation of dietary myristic acid (MA), palmitic acid (PA) and other substrates, healthy males (n=8) consumed prepared solid food diets containing 22% of energy as butter or tallow. Using a randomized cross-over design, subjects were prefed 11 day test diets which were identical in nutrient content except for the specific fat treatment. The diets provided 40%, 45%, and 15% of energy as fat, carbohydrate and protein, respectively, and were fed at a level equivalent to calculated energy requirements. On day 8 and day 11 of each diet cycle, a randomly assigned bolus of [1-¹³C]MA or [1-¹³C]PA (20 mg/kg body weight) was ingested with the breakfast meal. Hourly breath samples were collected for 9 hours thereafter and ¹³C0₂ enrichment was determined using isotope ratio mass spectrometry. Continuous respiratory gas exchange was also monitored and carbohydrate oxidation, fat oxidation and energy expenditure were determined. Treatment fat did not influence the fractional oxidation of dietary [1-¹³C]MA (% dose/9 hours; x±SEM; 7.1±1.0% and 8.6±0.9% after the butter and tallow meal, respectively) or [1-¹³C]PA (3.3±0.7% and 3.0±0.9% after the butter and tallow meal, respectively) (P<0.01, MA versus PA). MA contents of the butter and tallow meals were 4.6 g and 2.4 g, respectively, while the PA contents were 13.6 g and 11.2 g, respectively. While net dietary MA oxidation, calculated as the product of percent oxidation * meal fatty acid content, was greater (p<0.05) after the butter (329±45 mg) compared to tallow (212±25 mg) breakfast, no difference in net oxidation of dietary PA was observed between butter (441 ±99 mg) and tallow (348±95 mg) meals. Overall, dietary MA or PA accounted for less than 1% of fat oxidized for 9 hours postprandial. Cumulative postprandial energy expenditure (kcal/9 hours; 783±26 kcal and 781±31 kcal after the butter and tallow meal, respectively), cumulative postprandial fat oxidation (g/9 hours; 46±3 g and 44±4 g after the butter and tallow meal, respectively), and cumulative postprandial carbohydrate oxidation (g/9 hours; 85±8 g and 89±7 g after the butter and tallow meal, respectively) did not differ due to fat treatment. These findings suggest that the percent oxidation of MA and PA within a meal is independent of the blend of fatty acids consumed. However, it is markedly enhanced with decreasing chain length. Conversely, net oxidation of fatty acids contained within a meal is proportional to the mixture of fatty acids contained therein.Land and Food Systems, Faculty ofGraduat

Concurrent Session, Mission Accomplished: Community College Advisors Join Forces

In this session, you will learn how a small group of community college advising professionals came together over coffee & pastries to create a statewide collaborative effort that is striving to deliver effective advising on all our campuses. Participants will share best practices through active group dialogue following the presentation. Find out more how to become part of a movement that celebrates the uniqueness of community colleges and generates pivotal ideas on how you can support student success within and between colleagues. You will leave this session with a renewed sense of support and resources for your student success work. Although this session focuses on a community college initiative, it is open to everyone

Revised Description of the Early Permian Recumbirostran “Microsaur” Nannaroter mckinziei Based on New Fossil Material and Computed Tomographic Data

The early Permian Richards Spur locality of Oklahoma has produced abundant material of numerous terrestrial fossil tetrapods, including various “microsaurs,” several of which are considered to belong to the clade Recumbirostra. We present a new partial skull of the recumbirostran “microsaur” Nannaroter mckinziei; through computed tomography (CT) analysis of both this new specimen and the holotype, we provide an updated description of the taxon. This new description provides novel information regarding several regions that could not be examined previously due to either being absent in the holotype or difficult to access. This includes missing and obscured aspects of the skull roof, braincase, lower jaw, and the palatal region. Furthermore, the new information obtained from this description was used to update phylogenetic character codings of Nannaroter, and a revised phylogenetic analysis was conducted. The results of this updated analysis are congruent with those of other recent phylogenetic analyses of recumbirostran “microsaurs.” This new information adds to the ever-growing body of early tetrapod CT data, which has been, and will continue to be, important in revealing details regarding early tetrapod anatomy, interrelationships, paleoecology, and evolution.Peer Reviewe