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Objective. The present study was designed to evaluate the lipid-altering efficacy, safety, and tolerability of lovastatin treatment in adolescent girls with heterozygous familial hypercholesterolemia. Methods. A total of 54 postmenarchal girls, aged 10 to 17 years, were enrolled in a 24-week, double-blind, randomized, placebo-controlled study. After a 4-week diet/ placebo run-in period, patients were randomized to 1 of 2 groups: (1) treatment with diet plus lovastatin 20 mg/ day for 4 weeks, followed by diet plus lovastatin 40 mg/day for 20 weeks, or (2) diet plus placebo for 24 weeks. Results. Baseline values of lipids, lipoproteins, and apolipoproteins (apo) were comparable between treatment groups. Lovastatin treatment was efficacious at reducing low-density lipoprotein cholesterol by 23% to 27%, total cholesterol by 17% to 22%, and apo B by 20% to 23% at weeks 4 and 24, respectively. Between-treatment group differences were not statistically significant for triglycerides, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or apo A-I. Lovastatin was generally safe and well tolerated. There were no clinically significant alterations in vital signs (blood pressure and pulse rate), anthropomorphic measurements (height, weight, and BMI), hormone levels (luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone sulfate, estradiol, and cortisol), menstrual cycle length, or tests of liver and muscle function. Conclusions. Lovastatin offers an efficacious and well-tolerated treatment option for improving lipid profiles in adolescent gifts with familial hypercholesterolemia. Pediatrics 2005;116:682-688; adolescents, cholesterol, lipids., ABBREVIATIONS. CAD, coronary artery disease; TC, total cholesterol; LDL, low-density lipoprotein; HDL, high-density lipoprotein; FH, familial hypercholesterolemia; TG, triglycerides; VLDL, very-low-density lipoprotein; apo, apolipoprotein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; [...]

There are challenges in designing pediatric trials arising from special ethical issues and the relatively small accessible patient population. The application of conventional phase 3 trial designs to pediatrics is not realistic in some therapeutic areas. To address this issue, we propose various approaches for designing pediatric trials that incorporate data available from adult studies using James-Stein shrinkage estimation, empirical shrinkage estimation, and Bayesian methods. We also apply the concept of consistency used in multi-regional trials to pediatric trials. The performance of these methods is assessed through representative scenarios and an example using actual Type 2 diabetes mellitus (T2DM) trials. [ABSTRACT FROM AUTHOR]

The Food and Drug Administration (FDA) guidance for evaluating cardiovascular (CV) risk in new antidiabetic therapies to treat type 2 diabetes released in December 2008 recommends that sponsors conduct appropriate data analysis to rule out CV safety concerns for drugs treating type 2 diabetes. CV trials of antidiabetic drugs and drugs of other indications for chronic conditions are usually large-scale/long-term trials and can be designed as adaptive noninferiority/superiority trials. In these trials, treatment effect may not manifest immediately after patients take study medication and there will be a dilution in treatment effect after treatment discontinuation. These factors should be taken into account for more precise planning of study sample size and timeline. In this paper, we first derive closed-form formulas for the number of events and total exposure as functions of many other trial parameters. We then outline some considerations for the design of an adaptive noninferiority/superiority CV trial based on ideas of other authors. We also use an example to illustrate the application of the methods. [ABSTRACT FROM AUTHOR]

Background: Patients with elevated levels of serum triglycerides (TG) often have other associated lipid abnormalities (e.g., low levels of high-density lipoprotein cholesterol [HDL-C]) and are at increased risk of developing coronary heart disease. Although the therapeutic benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in hypercholesterolemic patients have been well established, less is known about the effects of statins in patient populations with hypertriglyceridemia., Hypothesis: The purpose of this study was to evaluate the lipoprotein-altering efficacy of simvastatin in hypertriglyceridemic patients., Methods: This was a multicenter, randomized, double-blind, placebo-controlled study. In all, 195 patients with fasting serum triglyceride levels between 300 and 900 mg/dl received once daily doses of placebo or simvastatin 20, 40, or 80 mg for 6 weeks., Results: Compared with placebo, simvastatin treatment across all doses resulted in significant reductions (p < 0.05 - < 0.001) in serum levels of triglycerides (-20 to -31% decrease) and TG-rich lipoprotein particles. Significant (p < 0.001) reductions were also seen in low-density lipoprotein cholesterol (-25 to -35%) and non-HDL-C (-26 to -40%). Levels of HDL-C were increased (7-11%) in the simvastatin groups compared with placebo (p < 0.05 - < 0.001)., Conclusion: The results of this study demonstrate the beneficial effects of simvastatin in patients with hypertriglyceridemia.