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Yale B Mitchel - One of the best experts on this subject based on the ideXlab platform.
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evaluation of lipids drug concentration and safety parameters following cessation of treatment with the cholesteryl ester transfer Protein Inhibitor anacetrapib in patients with or at high risk for coronary heart disease
American Journal of Cardiology, 2014Co-Authors: Antonio M. Gotto, Sukrut Shah, Hayes M Dansky, Eliot A. Brinton, Michael H Davidson, Uma Kher, Sanskruti Vaidya, Jennifer Moon, Yale B MitchelAbstract:The aim of this study was to assess the effects on lipids and safety during a 12-week reversal period after 18 months of treatment with anacetrapib. The cholesteryl ester transfer Protein Inhibitor anacetrapib was previously shown to reduce low-density lipoProtein cholesterol by 39.8% (estimated using the Friedewald equation) and increase high-density lipoProtein (HDL) cholesterol by 138.1%, with an acceptable side-effect profile, in patients with or at high risk for coronary heart disease in the Determining the Efficacy and Tolerability of CETP Inhibition With Anacetrapib (DEFINE) trial. A total of 1,398 patients entered the 12-week reversal-phase study, either after completion of the active-treatment phase or after early discontinuation of the study medication. In patients allocated to anacetrapib, placebo-adjusted mean percentage decreases from baseline were observed at 12 weeks off the study drug for Friedewald-calculated low-density lipoProtein cholesterol (18.6%), non-HDL cholesterol (17.6%), and apolipoProtein B (10.2%); placebo-adjusted mean percentage increases were observed for HDL cholesterol (73.0%) and apolipoProtein A-I (24.5%). Residual plasma anacetrapib levels (about 40% of on-treatment apparent steady-state trough levels) were also detected 12 weeks after cessation of anacetrapib. No clinically important elevations in liver enzymes, blood pressure, electrolytes, or adverse experiences were observed during the reversal phase. Preliminary data from a small cohort (n = 30) revealed the presence of low concentrations of anacetrapib in plasma 2.5 to 4 years after the last anacetrapib dose. In conclusion, after the cessation of active treatment, anacetrapib plasma lipid changes and drug levels decreased to approximately 40% of on-treatment trough levels at 12 weeks after dosing, but modest HDL cholesterol elevations and low drug concentrations were still detectable 2 to 4 years after the last dosing.
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abstract 15035 effects on lipids and safety following cessation of treatment with cholesteryl ester transfer Protein Inhibitor anacetrapib in patients with or at high risk for coronary heart disease
Circulation, 2011Co-Authors: Antonio M. Gotto, Sukrut Shah, Michael Stepanavage, Yale B Mitchel, Hayes M Dansky, Eliot A. Brinton, Michael H Davidson, Sherry Liu, Philip J BarterAbstract:The cholesteryl ester transfer Protein Inhibitor anacetrapib was shown to raise high-density lipoProtein (HDL) cholesterol and reduce low-density lipoProtein (LDL) cholesterol, with an acceptable s...
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efficacy and safety after cessation of treatment with the cholesteryl ester transfer Protein Inhibitor anacetrapib mk 0859 in patients with primary hypercholesterolemia or mixed hyperlipidemia
American Heart Journal, 2011Co-Authors: Hayes M Dansky, James M Mckenney, Christine Mccrary Sisk, Daniel M Bloomfield, Diane Tribble, Thomas W Littlejohn, Sherry Liu, Patrice H Gibbons, Yale B MitchelAbstract: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.
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efficacy and safety of the cholesteryl ester transfer Protein Inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients
American Heart Journal, 2009Co-Authors: Daniel M Bloomfield, Yale B Mitchel, James M Mckenney, Christine Mccrary Sisk, Gary Carlson, Aditi Sapre, Diane Tribble, Thomas W Littlejohn, Richard C PasternakAbstract:Background High-density lipoProtein cholesterol (HDL-C) levels are inversely associated with cardiovascular risk. Cholesteryl ester transfer Protein inhibition is one strategy for increasing HDL-C. This study evaluated the lipid-altering efficacy and safety of the cholesteryl ester transfer Protein Inhibitor anacetrapib as monotherapy or coadministered with atorvastatin in patients with dyslipidemia. Methods A total of 589 patients with primary hypercholesterolemia or mixed hyperlipidemia (53.8% of the study population had low HDL-C) were randomized equally to one of 10 groups: 5 groups received background statin therapy of atorvastatin 20 mg and 5 did not, and each of these was randomized to placebo, anacetrapib 10, 40, 150, and 300 mg once daily for 8 weeks. An equal proportion of patients had triglycerides >150 mg/dL in each group. Results For placebo and anacetrapib monotherapy (10, 40, 150, and 300 mg), least squares mean percent changes from baseline to week 8 for low-density lipoProtein cholesterol (LDL-C) were 2%, −16%, −27%, −40%, and −39%, respectively, and for HDL-C were 4%, 44%, 86%, 139%, and 133%, respectively ( P Conclusions Anacetrapib, as monotherapy or coadministered with atorvastatin, produced significant reductions in LDL-C and increases in HDL-C; the net result of treatment with anacetrapib + atorvastatin was ∼70% lowering of LDL-C and more than doubling of HDL-C. Anacetrapib was generally well tolerated with no discernable effect on blood pressure.
Daniel Gaudet - One of the best experts on this subject based on the ideXlab platform.
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Efficacy and safety of a microsomal triglyceride transfer Protein Inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study.
Lancet, 2013Co-Authors: Marina Cuchel, Hendrik Du Toit Theron, Maurizio R Averna, Dirk J. Blom, Emma A Meagher, Adrian David Marais, Prediman K Shah, Cesare R. Sirtori, Robert A. Hegele, Daniel GaudetAbstract:BACKGROUND Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs. We aimed to assess the efficacy and safety of the microsomal triglyceride transfer Protein Inhibitor lomitapide in adults with this disease. METHODS We did a single-arm, open-label, phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia. Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26. Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean percent change in levels of LDL cholesterol from baseline to week 26, after which patients remained on lomitapide through to week 78 for safety assessment. Percent change from baseline to week 26 was assessed with a mixed linear model. FINDINGS 29 men and women with homozygous familial hypercholesterolaemia, aged 18 years or older, were recruited from 11 centres in four countries (USA, Canada, South Africa, and Italy). 23 of 29 enrolled patients completed both the efficacy phase (26 weeks) and the full study (78 weeks). The median dose of lomitapide was 40 mg a day. LDL cholesterol was reduced by 50% (95% CI -62 to -39) from baseline (mean 8·7 mmol/L [SD 2·9]) to week 26 (4·3 mmol/L [2·5]; p
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Apheresis Treatment does not Affect the Lipid-Lowering Efficacy of Lomitapide, a Microsomal Triglyceride Transfer Protein Inhibitor, in Patients with Homozygous Familial Hypercholesterolemia
'Ovid Technologies (Wolters Kluwer Health)', 2012Co-Authors: Marina Cuchel, Hendrik Du Toit Theron, Emma A Meagher, Adrian David Marais, Prediman K Shah, Cesare R. Sirtori, Robert A. Hegele, Dirk Blom, Daniel GaudetAbstract:BACKGROUND: Patients with Homozygous Familial Hypercholesterolemia (HoFH) are at very high risk for premature cardiovascular disease and are refractory to existing lipid lowering drug therapy. Apheresis is considered standard of care for this condition. Lomitapide, a microsomal triglyceride transfer Protein Inhibitor, is currently under investigation for treatment of adults with HoFH. Previously reported results from the phase 3 study indicated that, in those who completed the efficacy phase, lomitapide significantly reduced LDL-C by about 50%. We report here results from a post hoc analysis to evaluate if apheresis treatment affects its lipid-lowering efficacy. METHODS: HoFH patients were enrolled into a single arm, open label study during which they were instructed to continue current lipid lowering therapy, including apheresis, unchanged from six weeks prior to baseline through week 26, the end of the efficacy phase. The primary endpoint was mean percent change from baseline of LDL-C at week 26 (intent to treat analysis). A mixed-models repeated measures analysis was used for analysis of the data. RESULTS: Of the 29 HoFH subjects enrolled, 18 were receiving either plasma or LDL apheresis and 11 were not. Twenty-three subjects (13 receiving apheresis) completed the week 26 evaluation. Baseline LDL-C levels in patients on apheresis and patients not on apheresis were 326± 108 mg/dL vs. 355 ± 125 mg/dL, respectively. LDL-C levels were reduced by 48% in subjects undergoing apheresis treatment and by 55% in subjects not on apheresis treatment (p=0.54). Similarly, no difference was observed for apo B (-48% vs. -53%, p=0.62), total cholesterol (-44% vs. -50%, p=0.58), triglycerides (-45% vs. -41%, p=0.78) or other lipoProtein parameters. CONCLUSIONS: These data indicate that lomitapide markedly reduced LDL-C and other apoB-containing lipoProtein parameters in patients with HoFH and its efficacy was independent of the use of apheresis treatment
Marina Cuchel - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of a microsomal triglyceride transfer Protein Inhibitor in patients with homozygous familial hypercholesterolaemia a single arm open label phase 3 study
The Lancet, 2013Co-Authors: Marina Cuchel, Hendrik Du Toit Theron, Dirk J. Blom, Emma A Meagher, Robert A. Hegele, David A Marais, Cesare R. SirtoriAbstract:Summary Background Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs. We aimed to assess the efficacy and safety of the microsomal triglyceride transfer Protein Inhibitor lomitapide in adults with this disease. Methods We did a single-arm, open-label, phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia. Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26. Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean percent change in levels of LDL cholesterol from baseline to week 26, after which patients remained on lomitapide through to week 78 for safety assessment. Percent change from baseline to week 26 was assessed with a mixed linear model. Findings 29 men and women with homozygous familial hypercholesterolaemia, aged 18 years or older, were recruited from 11 centres in four countries (USA, Canada, South Africa, and Italy). 23 of 29 enrolled patients completed both the efficacy phase (26 weeks) and the full study (78 weeks). The median dose of lomitapide was 40 mg a day. LDL cholesterol was reduced by 50% (95% CI −62 to −39) from baseline (mean 8·7 mmol/L [SD 2·9]) to week 26 (4·3 mmol/L [2·5]; p Interpretation Our study suggests that treatment with lomitapide could be a valuable drug in the management of homozygous familial hypercholesterolaemia. Funding FDA Office of the Orphan Product Development, Aegerion Pharmaceuticals.
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Efficacy and safety of a microsomal triglyceride transfer Protein Inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study.
Lancet, 2013Co-Authors: Marina Cuchel, Hendrik Du Toit Theron, Maurizio R Averna, Dirk J. Blom, Emma A Meagher, Adrian David Marais, Prediman K Shah, Cesare R. Sirtori, Robert A. Hegele, Daniel GaudetAbstract:BACKGROUND Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs. We aimed to assess the efficacy and safety of the microsomal triglyceride transfer Protein Inhibitor lomitapide in adults with this disease. METHODS We did a single-arm, open-label, phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia. Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26. Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean percent change in levels of LDL cholesterol from baseline to week 26, after which patients remained on lomitapide through to week 78 for safety assessment. Percent change from baseline to week 26 was assessed with a mixed linear model. FINDINGS 29 men and women with homozygous familial hypercholesterolaemia, aged 18 years or older, were recruited from 11 centres in four countries (USA, Canada, South Africa, and Italy). 23 of 29 enrolled patients completed both the efficacy phase (26 weeks) and the full study (78 weeks). The median dose of lomitapide was 40 mg a day. LDL cholesterol was reduced by 50% (95% CI -62 to -39) from baseline (mean 8·7 mmol/L [SD 2·9]) to week 26 (4·3 mmol/L [2·5]; p
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Apheresis Treatment does not Affect the Lipid-Lowering Efficacy of Lomitapide, a Microsomal Triglyceride Transfer Protein Inhibitor, in Patients with Homozygous Familial Hypercholesterolemia
'Ovid Technologies (Wolters Kluwer Health)', 2012Co-Authors: Marina Cuchel, Hendrik Du Toit Theron, Emma A Meagher, Adrian David Marais, Prediman K Shah, Cesare R. Sirtori, Robert A. Hegele, Dirk Blom, Daniel GaudetAbstract:BACKGROUND: Patients with Homozygous Familial Hypercholesterolemia (HoFH) are at very high risk for premature cardiovascular disease and are refractory to existing lipid lowering drug therapy. Apheresis is considered standard of care for this condition. Lomitapide, a microsomal triglyceride transfer Protein Inhibitor, is currently under investigation for treatment of adults with HoFH. Previously reported results from the phase 3 study indicated that, in those who completed the efficacy phase, lomitapide significantly reduced LDL-C by about 50%. We report here results from a post hoc analysis to evaluate if apheresis treatment affects its lipid-lowering efficacy. METHODS: HoFH patients were enrolled into a single arm, open label study during which they were instructed to continue current lipid lowering therapy, including apheresis, unchanged from six weeks prior to baseline through week 26, the end of the efficacy phase. The primary endpoint was mean percent change from baseline of LDL-C at week 26 (intent to treat analysis). A mixed-models repeated measures analysis was used for analysis of the data. RESULTS: Of the 29 HoFH subjects enrolled, 18 were receiving either plasma or LDL apheresis and 11 were not. Twenty-three subjects (13 receiving apheresis) completed the week 26 evaluation. Baseline LDL-C levels in patients on apheresis and patients not on apheresis were 326± 108 mg/dL vs. 355 ± 125 mg/dL, respectively. LDL-C levels were reduced by 48% in subjects undergoing apheresis treatment and by 55% in subjects not on apheresis treatment (p=0.54). Similarly, no difference was observed for apo B (-48% vs. -53%, p=0.62), total cholesterol (-44% vs. -50%, p=0.58), triglycerides (-45% vs. -41%, p=0.78) or other lipoProtein parameters. CONCLUSIONS: These data indicate that lomitapide markedly reduced LDL-C and other apoB-containing lipoProtein parameters in patients with HoFH and its efficacy was independent of the use of apheresis treatment
Cesare R. Sirtori - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of a microsomal triglyceride transfer Protein Inhibitor in patients with homozygous familial hypercholesterolaemia a single arm open label phase 3 study
The Lancet, 2013Co-Authors: Marina Cuchel, Hendrik Du Toit Theron, Dirk J. Blom, Emma A Meagher, Robert A. Hegele, David A Marais, Cesare R. SirtoriAbstract:Summary Background Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs. We aimed to assess the efficacy and safety of the microsomal triglyceride transfer Protein Inhibitor lomitapide in adults with this disease. Methods We did a single-arm, open-label, phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia. Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26. Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean percent change in levels of LDL cholesterol from baseline to week 26, after which patients remained on lomitapide through to week 78 for safety assessment. Percent change from baseline to week 26 was assessed with a mixed linear model. Findings 29 men and women with homozygous familial hypercholesterolaemia, aged 18 years or older, were recruited from 11 centres in four countries (USA, Canada, South Africa, and Italy). 23 of 29 enrolled patients completed both the efficacy phase (26 weeks) and the full study (78 weeks). The median dose of lomitapide was 40 mg a day. LDL cholesterol was reduced by 50% (95% CI −62 to −39) from baseline (mean 8·7 mmol/L [SD 2·9]) to week 26 (4·3 mmol/L [2·5]; p Interpretation Our study suggests that treatment with lomitapide could be a valuable drug in the management of homozygous familial hypercholesterolaemia. Funding FDA Office of the Orphan Product Development, Aegerion Pharmaceuticals.
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Efficacy and safety of a microsomal triglyceride transfer Protein Inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study.
Lancet, 2013Co-Authors: Marina Cuchel, Hendrik Du Toit Theron, Maurizio R Averna, Dirk J. Blom, Emma A Meagher, Adrian David Marais, Prediman K Shah, Cesare R. Sirtori, Robert A. Hegele, Daniel GaudetAbstract:BACKGROUND Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs. We aimed to assess the efficacy and safety of the microsomal triglyceride transfer Protein Inhibitor lomitapide in adults with this disease. METHODS We did a single-arm, open-label, phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia. Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26. Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean percent change in levels of LDL cholesterol from baseline to week 26, after which patients remained on lomitapide through to week 78 for safety assessment. Percent change from baseline to week 26 was assessed with a mixed linear model. FINDINGS 29 men and women with homozygous familial hypercholesterolaemia, aged 18 years or older, were recruited from 11 centres in four countries (USA, Canada, South Africa, and Italy). 23 of 29 enrolled patients completed both the efficacy phase (26 weeks) and the full study (78 weeks). The median dose of lomitapide was 40 mg a day. LDL cholesterol was reduced by 50% (95% CI -62 to -39) from baseline (mean 8·7 mmol/L [SD 2·9]) to week 26 (4·3 mmol/L [2·5]; p
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Apheresis Treatment does not Affect the Lipid-Lowering Efficacy of Lomitapide, a Microsomal Triglyceride Transfer Protein Inhibitor, in Patients with Homozygous Familial Hypercholesterolemia
'Ovid Technologies (Wolters Kluwer Health)', 2012Co-Authors: Marina Cuchel, Hendrik Du Toit Theron, Emma A Meagher, Adrian David Marais, Prediman K Shah, Cesare R. Sirtori, Robert A. Hegele, Dirk Blom, Daniel GaudetAbstract:BACKGROUND: Patients with Homozygous Familial Hypercholesterolemia (HoFH) are at very high risk for premature cardiovascular disease and are refractory to existing lipid lowering drug therapy. Apheresis is considered standard of care for this condition. Lomitapide, a microsomal triglyceride transfer Protein Inhibitor, is currently under investigation for treatment of adults with HoFH. Previously reported results from the phase 3 study indicated that, in those who completed the efficacy phase, lomitapide significantly reduced LDL-C by about 50%. We report here results from a post hoc analysis to evaluate if apheresis treatment affects its lipid-lowering efficacy. METHODS: HoFH patients were enrolled into a single arm, open label study during which they were instructed to continue current lipid lowering therapy, including apheresis, unchanged from six weeks prior to baseline through week 26, the end of the efficacy phase. The primary endpoint was mean percent change from baseline of LDL-C at week 26 (intent to treat analysis). A mixed-models repeated measures analysis was used for analysis of the data. RESULTS: Of the 29 HoFH subjects enrolled, 18 were receiving either plasma or LDL apheresis and 11 were not. Twenty-three subjects (13 receiving apheresis) completed the week 26 evaluation. Baseline LDL-C levels in patients on apheresis and patients not on apheresis were 326± 108 mg/dL vs. 355 ± 125 mg/dL, respectively. LDL-C levels were reduced by 48% in subjects undergoing apheresis treatment and by 55% in subjects not on apheresis treatment (p=0.54). Similarly, no difference was observed for apo B (-48% vs. -53%, p=0.62), total cholesterol (-44% vs. -50%, p=0.58), triglycerides (-45% vs. -41%, p=0.78) or other lipoProtein parameters. CONCLUSIONS: These data indicate that lomitapide markedly reduced LDL-C and other apoB-containing lipoProtein parameters in patients with HoFH and its efficacy was independent of the use of apheresis treatment
Dirk J. Blom - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of a microsomal triglyceride transfer Protein Inhibitor in patients with homozygous familial hypercholesterolaemia a single arm open label phase 3 study
The Lancet, 2013Co-Authors: Marina Cuchel, Hendrik Du Toit Theron, Dirk J. Blom, Emma A Meagher, Robert A. Hegele, David A Marais, Cesare R. SirtoriAbstract:Summary Background Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs. We aimed to assess the efficacy and safety of the microsomal triglyceride transfer Protein Inhibitor lomitapide in adults with this disease. Methods We did a single-arm, open-label, phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia. Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26. Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean percent change in levels of LDL cholesterol from baseline to week 26, after which patients remained on lomitapide through to week 78 for safety assessment. Percent change from baseline to week 26 was assessed with a mixed linear model. Findings 29 men and women with homozygous familial hypercholesterolaemia, aged 18 years or older, were recruited from 11 centres in four countries (USA, Canada, South Africa, and Italy). 23 of 29 enrolled patients completed both the efficacy phase (26 weeks) and the full study (78 weeks). The median dose of lomitapide was 40 mg a day. LDL cholesterol was reduced by 50% (95% CI −62 to −39) from baseline (mean 8·7 mmol/L [SD 2·9]) to week 26 (4·3 mmol/L [2·5]; p Interpretation Our study suggests that treatment with lomitapide could be a valuable drug in the management of homozygous familial hypercholesterolaemia. Funding FDA Office of the Orphan Product Development, Aegerion Pharmaceuticals.
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Efficacy and safety of a microsomal triglyceride transfer Protein Inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study.
Lancet, 2013Co-Authors: Marina Cuchel, Hendrik Du Toit Theron, Maurizio R Averna, Dirk J. Blom, Emma A Meagher, Adrian David Marais, Prediman K Shah, Cesare R. Sirtori, Robert A. Hegele, Daniel GaudetAbstract:BACKGROUND Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs. We aimed to assess the efficacy and safety of the microsomal triglyceride transfer Protein Inhibitor lomitapide in adults with this disease. METHODS We did a single-arm, open-label, phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia. Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26. Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean percent change in levels of LDL cholesterol from baseline to week 26, after which patients remained on lomitapide through to week 78 for safety assessment. Percent change from baseline to week 26 was assessed with a mixed linear model. FINDINGS 29 men and women with homozygous familial hypercholesterolaemia, aged 18 years or older, were recruited from 11 centres in four countries (USA, Canada, South Africa, and Italy). 23 of 29 enrolled patients completed both the efficacy phase (26 weeks) and the full study (78 weeks). The median dose of lomitapide was 40 mg a day. LDL cholesterol was reduced by 50% (95% CI -62 to -39) from baseline (mean 8·7 mmol/L [SD 2·9]) to week 26 (4·3 mmol/L [2·5]; p
