Phase I Study of the Safety, Tolerability, PK & PD of Lomitapide in Japanese and Caucasian Subjects With Elevated LDL-C
Condition: Healthy Volunteer
Intervention: lomitapide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 72.0
Sex: All
Minimum age: 20 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) and
      multiple ascending dose (MAD) study of orally administered lomitapide in healthy male
      Japanese and Caucasian subjects with elevated LDL-C. The purpose for this study is to
      evaluate the PK and PD of lomitapide in Japanese subjects as compared to Caucasian subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  1. Subject is a healthy male or female, Caucasian or Japanese, aged 20 - 45 years,
             inclusive, at screening.

             2. Subject has a BMI of 18.5 - 30 kg/m2 inclusive at screening.

             3. 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.

             4. Subjects must agree to use acceptable methods of contraception (details provided in
             the protocol)

             5. 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:

          1. Subject has a clinically significant disease or any condition or disease that might
             affect drug absorption, distribution or excretion.

          2. 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.

          3. 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.

          4. History or current evidence of any clinically relevant cardiovascular, pulmonary,
             hepatic, renal, gastrointestinal, haematological, endocrinological, metabolic,
             neurological, psychiatric or other disease.

          5. 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.

          6. Confirmed positive results from urine drug screen or from the alcohol breath test at
             screening and on admission (Day -1).

          7. History or clinical evidence of alcohol or drug abuse.

          8. Mentally handicapped.

          9. Participation in a drug trial within 90 days prior to first drug administration.

         10. 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.

         11. Use of any substance inhibiting CYP3A4 enzymes within 2 weeks prior to admission (Day
             -1).

         12. Donation of more than 500 mL of blood within 90 days prior to drug administration.

         13. 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.

         14. Treatment with herbal supplements during the 7 days prior to dosing, or use of
             vitamins during 48 hours prior to admission (Day -1).

         15. Any circumstances or conditions, which, in the opinion of the PI, may affect full
             participation in the trial or compliance with the protocol.

         16. Legal incapacity or limited legal capacity at screening.

         17. Subjects who are vegetarians, vegans or have any dietary restrictions conflicting with
             the study standardised menus.

         18. If female, subject was pregnant or lactating (females of child bearing potential must
             have negative pregnancy tests at screening and admission).