Diane Tribble
Merck & Co.
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Featured researches published by Diane Tribble.
Metabolism-clinical and Experimental | 2008
Diane Tribble; Michel Farnier; Geraldine Macdonell; Inna Perevozskaya; Michael J. Davies; Barry Gumbiner; Thomas Musliner
Coadministration of fenofibrate and ezetimibe (FENO + EZE) produced complementary and favorable effects on the major lipids and lipoproteins, low-density lipoprotein cholesterol (LDL-C), triglycerides, high-density lipoprotein cholesterol (HDL-C), and non-HDL-C levels, and was well tolerated in patients with mixed hyperlipidemia. The current analysis evaluates the effects of FENO and EZE, as monotherapies and in coadministration, on lipoprotein subfractions and LDL particle size distributions in these patients. In a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients with mixed hyperlipidemia were randomized in a 1:3:3:3 ratio to one of 4 treatment groups: placebo, FENO 160 mg/day, EZE 10 mg/day, or FENO 160 mg/day + EZE 10 mg/day. At baseline and study end point, the Vertical Auto Profile II method was used to measure the cholesterol associated with 2 very low-density lipoprotein (VLDL) subfractions (VLDL-C1 + 2 and VLDL-C3), intermediate-density lipoproteins (IDL-C), and 4 LDL subfractions (LDL-C1 through LDL-C4, from most buoyant to most dense), lipoprotein (Lp) (a), and 2 HDL-C subfractions (HDL-C2 and HDL-C3). The LDL particle size was determined using segmented gradient gel electrophoresis. Fenofibrate reduced cholesterol mass within VLDL, IDL, and dense LDL (primarily LDL-C4) subfractions, and increased cholesterol mass within the more buoyant LDL-C2 subfraction, consistent with a shift to a more buoyant LDL peak particle size. Ezetimibe reduced cholesterol mass within all of the apolipoprotein B-containing particles (eg, VLDL-C, IDL-C, and LDL-C) but did not lead to a shift in the LDL particle size distribution profile. Coadministration of FENO and EZE promoted more pronounced reductions in VLDL-C, IDL-C, and LDL-C, and a preferential decrease in dense LDL subfractions. Fenofibrate and FENO + EZE promoted similar increases in HDL-C2 and HDL-C3. Coadministration of FENO + EZE produced complementary and favorable changes in lipoprotein fractions and subfractions, as assessed by the Vertical Auto Profile II method, in patients with mixed hyperlipidemia. These changes reflected the combined effects of FENO in reducing triglycerides-rich lipoproteins and promoting a shift in the LDL particle distribution profile toward larger, more buoyant particles and of EZE in promoting reductions in cholesterol mass across the apolipoprotein B particle spectrum.
American Heart Journal | 2011
Hayes M. Dansky; Daniel M. Bloomfield; Patrice H. Gibbons; Sherry Liu; Christine McCrary Sisk; Diane Tribble; James M. McKenney; Thomas W. Littlejohn; Yale B. Mitchel
This report describes the lipid and safety data collected during an off-drug period that followed 8 weeks of treatment with the cholesteryl ester transfer protein inhibitor, anacetrapib (ANA). A total of 589 patients with primary hypercholesterolemia or mixed hyperlipidemia were randomized to placebo, atorvastatin (ATV) 20 mg, and varying doses of ANA, provided as monotherapy or coadministered with ATV 20 mg daily. Patients were treated for 8 weeks, followed by an 8-week follow-up period, during which ANA was switched to placebo. At week 16 (8 weeks after ANA was stopped), persistent reductions in low-density lipoprotein cholesterol (LDL-C) were evident for the monotherapy groups receiving ANA 150 and 300 mg (-9.3% and -15.3%, respectively), and residual increases in high-density lipoprotein cholesterol (HDL-C) were observed for the monotherapy groups receiving ANA 40 mg (18.6%), 150 mg (40.5%), and 300 mg (43.4%). The effects on apolipoprotein B and apolipoprotein A-I were consistent with the changes observed for LDL-C and HDL-C, respectively. Corresponding residual changes in LDL-C and HDL-C were also noted in the ATV coadministration groups at the similar doses of ANA compared with ATV 20 mg alone. Residual plasma drug levels accompanied by reductions in cholesteryl ester transfer protein activity were observed at week 16 and may account for the alterations in plasma lipids 8 weeks after cessation of ANA.
Current Medical Research and Opinion | 2006
Leiv Ose; Arvind Shah; Michael J. Davies; Jennifer Rotonda; Darbie Maccubbin; Diane Tribble; Enrico P. Veltri; Yale B. Mitchel
ABSTRACT Background: The combination tablet containing ezetimibe and simvastatin (EZE/SIMVA), inhibits both the intestinal absorption and endogenous production of cholesterol, providing significantly greater low-density lipoprotein cholesterol (LDL-C) lowering than EZE or SIMVA alone. The purpose of this pooled analysis was to evaluate the consistency of efficacy (i.e., between-treatment difference) of EZE/SIMVA versus SIMVA within several selected subgroups of patients with primary hypercholesterolemia. Methods: For the present analysis, data were pooled from three similarly designed, 12‐week, randomized, double-blind, placebo-controlled factorial studies consisting of 3083 patients with primary hypercholesterolemia (u2009n = 311 in placebo group; n = 302 in EZE group; n = 1234 in pooled SIMVA group; n = 1236 in pooled EZE/SIMVA group). In these clinical studies, primary hypercholesterolemia was defined as an LDL‐C value between 145 and 250u2009mg/dL inclusive and a triglyceride (TG) level of less than 350u2009mg/dL. The results for the pooled SIMVA and pooled EZE/SIMVA groups were used for the present analyses. The pooled analyses focused on the consistency of the between-treatment differences (i.e., incremental effect) for EZE/SIMVA (pooled across doses) versus SIMVA (pooled across doses) on various lipid and non-lipid parameters within different patient subgroups defined according to gender, race (Caucasian, Non-Caucasian), baseline age (< 65, ≥ 65 years), baseline LDL‐C (< 160, ≥ 160u2009mg/dL), and coronary heart disease (CHD) history. Tolerability was also examined for pooled EZE/SIMVA and pooled SIMVA within these selected subgroups. In a modified intention-to-treat analysis, an ANOVA model was used for testing the consistency of pooled treatment effects on lipid and non-lipid parameters within each selected subgroup. Results: For the entire cohort, baseline lipid profiles were similar for the patients in the pooled EZE/SIMVA group compared with those in the pooled SIMVA group. Treatment with EZE/SIMVA led to significant (u2009p < 0.001) incremental improvements in LDL‐C, non-high density lipoprotein cholesterol (non-HDL‐C), apolipoprotein B, TG and high sensitivity C‐reactive protein compared to SIMVA, across the entire cohort. These changes were consistent within each of the selected subgroups. Moreover, more patients attained LDL‐C goal levels < 100u2009mg/dL with EZE/SIMVA than with SIMVA in the entire cohort and this was consistent across all subgroups, except baseline LDL‐C. In this pooled retrospective analysis, treatment with EZE/SIMVA was generally well tolerated across subgroups, with a safety profile similar to SIMVA monotherapy. Although this pooled analysis was performed on a large cohort of patients with primary hypercholesterolemia, the results of this analysis were specific for this select patient population and generalizations to other populations should be applied with caution. Conclusion: The enhanced lipid-altering effects of EZE/SIMVA versus those of SIMVA observed in the entire cohort were consistent within all subgroups examined. EZE/SIMVA represents an effective and well-tolerated therapeutic option for the treatment of a wide range of patient subgroups with primary hypercholesterolemia.
Metabolic Syndrome and Related Disorders | 2007
Ted Feldman; Leiv Ose; Arvind Shah; Michelle Zakson; Alan G. Meehan; Amy O. Johnson-Levonas; Darbie Maccubbin; Diane Tribble; Enrico P. Veltri; Yale B. Mitchel
BACKGROUNDnThe combination of ezetimibe and simvastatin (EZE/SIMVA) inhibits intestinal absorption and hepatic synthesis of cholesterol, providing significantly greater LDL-C-lowering compared to either drug alone. We examined the efficacy and safety of EZE/SIMVAin hypercholesterolemic patients with metabolic syndrome (MetS).nnnMETHODSnWe evaluated pooled data from three similarly designed, randomized, doubleblinded, placebo-controlled studies in patients with primary hypercholesterolemia. After a 6- to 8-week washout and a 4-week diet/placebo run-in, patients received one of the following treatments for 12 weeks: EZE/SIMVA (10/10, 10/20, 10/40 or 10/80 mg); SIMVA (10, 20, 40 or 80 mg); EZE 10 mg; or placebo. For this analysis, the efficacy of EZE/SIMVA versus SIMVA was evaluated in patients with and without MetS. The primary endpoint was mean percent change from baseline in LDL-C for EZE/SIMVA (pooled across doses) versus SIMVA (pooled across doses).nnnRESULTSnOf 2394 patients who received SIMVA or EZE/SIMVA and for whom MetS status at baseline could be determined, 31% were identified as having MetS. In the entire cohort, treatment with EZE/SIMVA led to a significant incremental reduction in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, triglyceride (TG), and C-reactive protein compared to SIMVA and these effects were similar across the MetS and non-MetS subgroups. EZE/SIMVA was well tolerated in both the MetS and non-MetS subgroups.nnnCONCLUSIONnEZE/SIMVA significantly improved the lipid and inflammatory profiles of hypercholesterolemic patients with MetS and was well tolerated. Thus, EZE/SIMVA offers an efficacious and safe treatment option for these patients.
International Journal of Clinical Practice | 2007
L. Ose; Amy O. Johnson-Levonas; Robert Reyes; Jianxin Lin; Arvind Shah; Diane Tribble; Thomas Musliner
The objective of this study was to compare the efficacy and safety profile of ezetimibe/simvastatin (EZE/SIMVA) tablet and SIMVA monotherapy. This was an extension study of a randomised, double‐blind, placebo‐controlled study in patients with primary hypercholesterolaemia. Protocol‐compliant patients who completed the 12‐week base study were eligible to enter a randomised, double‐blind, 14‐week extension study and were administered 1 of 8 daily treatments: EZE/SIMVA 10/10‐, 10/20‐, 10/40‐ or 10/80‐mg, or SIMVA 10‐, 20‐, 40‐ or 80‐mg. Patients receiving these treatments during the base study remained on the same treatment in the extension. Patients administered placebo or EZE 10‐mg monotherapy during the base study were re‐randomised to EZE/SIMVA 10/10u2003mg or SIMVA 80u2003mg. The primary analysis was mean per cent change in low‐density lipoprotein cholesterol (LDL‐C) from baseline to extension study end‐point. Mean changes from baseline in LDL‐C of −38.8% and −53.7% were observed for pooled SIMVA and pooled EZE/SIMVA respectively. The between treatment difference of −14.9% (95% confidence interval: −16.4, −13.3) was statistically significant (pu2003<u20030.001). The incremental LDL‐C lowering effect of EZE/SIMVA compared with the corresponding dose of SIMVA alone was consistent across the dose range (pu2003<u20030.001 for each between‐group comparison). More patients receiving EZE/SIMVA than SIMVA achieved LDL‐C concentrations <u2003100u2003mg/dl and <u200370u2003mg/dl (pu2003<u20030.001 for both goals). EZE/SIMVA was generally well tolerated with a safety profile similar to SIMVA monotherapy. There were no significant between‐group differences in the incidences of clinically significant elevations in liver transaminase or creatine kinase levels. In conclusion, EZE/SIMVA had a comparable safety and tolerability profile and was more efficacious than SIMVA monotherapy for up to 6u2003months.
Clinical Therapeutics | 2004
Harold E. Bays; Leiv Ose; Neil Fraser; Diane Tribble; Katherine Quinto; Robert Reyes; Amy O. Johnson-Levonas; Aditi Sapre; Steven R. Donahue
Clinical Therapeutics | 2007
Leiv Ose; Robert Reyes; Amy O. Johnson-Levonas; Aditi Sapre; Diane Tribble; Thomas Musliner
Clinical Therapeutics | 2006
Ted Feldman; Michael Davidson; Arvind Shah; Darbie Maccubbin; Alan G. Meehan; Michelle Zakson; Diane Tribble; Enrico P. Veltri; Yale B. Mitchel
Journal of the American College of Cardiology | 2004
Gerd Assmann; Frank Kannenberg; Wayne Weng; John Erbey; Ani John; Diane Tribble; Thomas Musliner; Lesli Lipka; Enrico P. Veltri
Journal of the American College of Cardiology | 2004
Harold E. Bays; Leiv Ose; Neil Fraser; Katherine Quinto; Robert Reyes; Aditi Sapre; Diane Tribble; Stephen Donahue