Clinical trial NCT01760187: Phase I Study of the Safety, Tolerability, PK & PD of Lomitapide in Japanese and Caucasian Subjects With Elevated LDL-C
Official title: A Randomized, Double-blind, Placebo-controlled, Single Ascending and Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics(PK) and Pharmacodynamics(PD) of Lomitapide in Japanese and Caucasian Volunteers With Elevated Low-density-lipoprotein(LDL-C)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Aegerion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Richmond Pharmacology Limited
First posted: 2013-01-04
Enrollment: 72
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Primary outcomes:
measure: Cmax for Lomitapide
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: Tmax for Lomitapide
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: AUC0-t for Lomitapide
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: AUC0-∞ for Lomitapide
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: t1/2 for Lomitapide
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: Cmax for Lomitapide
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
measure: Tmax for Lomitapide
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
measure: AUC0-t for Lomitapide
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
measure: t1/2 for Lomitapide
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
Secondary outcomes:
measure: Cmax for M1
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: Tmax for M1
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: AUC0-t for M1
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: AUC0-∞ for M1
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: t1/2 for M1
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: Cmax for M3
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: Tmax for M3
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: AUC0-t for M3
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: AUC0-∞ for M3
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: t1/2 for M3
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
measure: Cmax for M1
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
measure: Tmax for M1
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
measure: AUC0-t for M1
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
measure: t1/2 for M1
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
measure: Cmax for M3
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
measure: Tmax for M3
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
measure: AUC0-t for M3
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
measure: t1/2 for M3
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
Other outcomes:
Locations:
city: Croydon
country: United Kingdom
facility: Richmond Pharmacology Ltd
state: Surrey
Study officials:
affiliation: Richmond Pharmacology Limited
name: Ulrike Lorch, MD FRCA FFPM
role: PRINCIPAL_INVESTIGATOR
References: