Study to Determine the Intra-subject Variability of Pharmacokinetics of Lomitapide in Healthy Subjects

This study will be a single centre, open-label study. It will comprise of 2 single oral doses with at least a 14-day washout between doses. Following the first dose subjects will be discharged from the unit for the remainder of the washout period. Subjects will be re-admitted to the unit on Day -1 (Period 2) and following an overnight fast they will be administered the second dose on Day 1 (Period 2). Subjects will be discharged from the unit following the 168 h PK blood draw.

Inclusion criteria

• Subject is a non-smoking healthy male or female, aged between 18 and 40 years of age.
• Subject has a BMI of 18.5 - 25 kg/m2.
• Subject has total body weight between > 50 kg to ≤ 100 kg.
• Subjects must agree to use acceptable methods of contraception.
• All females, regardless of childbearing potential, must have a negative serum beta human chorionic gonadotropin pregnancy test at Screening and on admission.
• In good health, determined by no clinically significant or relevant abnormalities identified by a detailed medical history & full physical examination.
• No known history of hypersensitivity or previous intolerance to lomitapide.
• 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.
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs.
• Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator;
• Electrocardiogram (ECG) abnormalities in the standard 12-lead ECG (at screening) such as a QTcF interval of >450 msec, a history of a prolonged QTc interval or Brugada syndrome.
• History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrinological, allergic, dermatological, metabolic, neurological, psychiatric or other disease.
• History or laboratory evidence of Gilbert's syndrome.
• 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).
• Use of any drugs of abuse within 6 months prior to admission.
• Confirmed positive results from urine drug screen (amphetamines, benzodiazepines, cocaine, cannabinoids, opiates, barbiturates and methadone) or from the alcohol breath test at screening and on admission (Day -1).
• History or clinical evidence of alcohol or drug abuse within one year prior to admission.
• Mentally handicapped.
• Participation in a drug trial within 90 days prior to first drug administration.
• Use of any prescription medication within 2 weeks prior to admission (Day -1), with the exception of the oral contraceptive pill.
• Use of any substance inducing or inhibiting CYP3A4 enzymes within 30 days prior to admission (Day -1).
• Use of any over-the-counter (OTC) medication (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days prior to admission (Day -1), unless deemed acceptable by the Investigator and Sponsor.
• Use of alcohol-, grapefruit-, starfruit-, or caffeine-containing foods or beverages within 72 hours prior to admission and through Study Completion.
• Donation of more than 500 mL of blood within 90 days prior to drug administration.
• Receipt of blood products within 2 months prior to admission.
• Poor peripheral venous access.
• Use of any tobacco- or nicotine-containing products within 6 months prior to admission (Day -1).
• Any acute or chronic condition, scheduled hospitalisation (inclusive of elective surgery during study), or scheduled travel prior to completion of all study procedures.
• 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.