AIMS: Lomitapide is a licensed treatment for patients with homozygous familial hypercholesterolaemia in the USA, the EU, Canada, and Mexico. This study was conducted to compare the pharmacokinetics (PK), pharmacodynamics, safety, and tolerability of lomitapide between Japanese and Caucasian subjects with elevated low-density lipoprotein cholesterol (LDL-C) after single and multiple doses. METHODS: In this randomized, double-blind, placebo-controlled study, 36 Japanese and 36 Caucasian subjects with LDL-C levels ≥110 mg/dL were administered an escalating lomitapide dose range of 10-60 mg or placebo. Subjects were assessed for safety, tolerability, and lipid levels. RESULTS: Exposure to lomitapide as measured by Cmax was linear and increased over the dose range of 10-60 mg for both single- and multiple-dose administration. The correlation between AUC0-t and Ctrough demonstrated the lack of differences in the PK of lomitapide among ethnic groups. Lomitapide dose-dependent reductions in lipid parameters were observed and showed no ethnic differences. The safety assessments showed that the main treatment-related side effects identified were increases in hepatic enzymes and that the majority of treatment-related treatment-emergent AEs were gastrointestinal disorders. CONCLUSIONS:Lomitapide was effective in reducing LDL-C levels in a dose-dependent manner. Similar PK, efficacy, and safety profiles were observed in Japanese and Caucasian subjects, which suggest no differences in lomitapide activity or metabolism between the two populations compared in this study.
RCT Entities:
AIMS: Lomitapide is a licensed treatment for patients with homozygous familial hypercholesterolaemia in the USA, the EU, Canada, and Mexico. This study was conducted to compare the pharmacokinetics (PK), pharmacodynamics, safety, and tolerability of lomitapide between Japanese and Caucasian subjects with elevated low-density lipoprotein cholesterol (LDL-C) after single and multiple doses. METHODS: In this randomized, double-blind, placebo-controlled study, 36 Japanese and 36 Caucasian subjects with LDL-C levels ≥110 mg/dL were administered an escalating lomitapide dose range of 10-60 mg or placebo. Subjects were assessed for safety, tolerability, and lipid levels. RESULTS: Exposure to lomitapide as measured by Cmax was linear and increased over the dose range of 10-60 mg for both single- and multiple-dose administration. The correlation between AUC0-t and Ctrough demonstrated the lack of differences in the PK of lomitapide among ethnic groups. Lomitapide dose-dependent reductions in lipid parameters were observed and showed no ethnic differences. The safety assessments showed that the main treatment-related side effects identified were increases in hepatic enzymes and that the majority of treatment-related treatment-emergent AEs were gastrointestinal disorders. CONCLUSIONS:Lomitapide was effective in reducing LDL-C levels in a dose-dependent manner. Similar PK, efficacy, and safety profiles were observed in Japanese and Caucasian subjects, which suggest no differences in lomitapide activity or metabolism between the two populations compared in this study.