Phase I Study of the Safety, Tolerability, PK & PD of Lomitapide in Japanese and Caucasian Subjects With Elevated LDL-C

Inclusion criteria

• 1. Subject is a healthy male or female, Caucasian or Japanese, aged 20 - 45 years, inclusive, at screening.

• Subject has a BMI of 18.5 - 30 kg/m2 inclusive at screening.

• Subjects must have a screening LDL-C measurement and the mean of Day 5 and Day 6 measurements greater than or equal to 110mg/dL.

• Subjects must agree to use acceptable methods of contraception (details provided in the protocol)

• Subjects must be capable of understanding and complying with the requirements of the protocol and must have signed the informed consent form prior to undergoing any study-related procedures.

Exclusion criteria

• Subject has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion.
• Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations conducted at screening or on admission.
• Electrocardiogram (ECG) abnormalities in the standard 12-lead ECG (at screening) which in the opinion of the Investigator is clinically relevant or will interfere with the ECG analysis.
• History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrinological, metabolic, neurological, psychiatric or other disease.
• Positive results in any of the serology tests for Hepatitis B Surface Antigen (HbsAg), anti-Hepatitis core antibody (anti-HBc Ig G [and anti-HBc IgM if IgG is positive], Hepatitis C antibodies (anti-HCV), and HIV 1 and 2 antibodies, (anti-HIV 1/2) at screening.
• Confirmed positive results from urine drug screen or from the alcohol breath test at screening and on admission (Day -1).
• History or clinical evidence of alcohol or drug abuse.
• Mentally handicapped.
• Participation in a drug trial within 90 days prior to first drug administration.
• Use of any medication (including over-the-counter (OTC) medication) within 2 weeks prior to admission (Day -1) or within less than 10 times the elimination half-life of the respective drug, or anticipated concomitant medication during the treatment periods.
• Use of any substance inhibiting CYP3A4 enzymes within 2 weeks prior to admission (Day -1).
• Donation of more than 500 mL of blood within 90 days prior to drug administration.
• Subjects who smoke more than 10 cigarettes or equivalent amount of tobacco per day and/or who cannot stop smoking for the duration of the study whilst in the CPU.
• Treatment with herbal supplements during the 7 days prior to dosing, or use of vitamins during 48 hours prior to admission (Day -1).
• Any circumstances or conditions, which, in the opinion of the PI, may affect full participation in the trial or compliance with the protocol.
• Legal incapacity or limited legal capacity at screening.
• Subjects who are vegetarians, vegans or have any dietary restrictions conflicting with the study standardised menus.
• If female, subject was pregnant or lactating (females of child bearing potential must have negative pregnancy tests at screening and admission).