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

Sponsor

Aegerion Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01760187

Collaborator

Richmond Pharmacology Limited (Industry)

Enrollment

Location

Arms

6.8

Actual Duration (Months)

10.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteer	Drug: lomitapide	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Nov 7, 2012

Actual Primary Completion Date :

Jun 3, 2013

Actual Study Completion Date :

Jun 3, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 12 Japanese and 12 Caucasian subjects. 10 out of 12 will receive 10 mg lomitapide and 2 will receive placebo.	Drug: lomitapide
Experimental: Cohort 2 8 Japanese and 8 Caucasian subjects. 6 out of 8 subjects will receive 20 mg lomitapide and 2 will receive placebo.	Drug: lomitapide
Experimental: Cohort 3 8 Japanese and 8 Caucasian subjects. 6 out of 8 subjects will receive 40 mg lomitapide and 2 will receive placebo.	Drug: lomitapide
Experimental: Cohort 4 8 Japanese and 8 Caucasian subjects. 6 out of 8 subjects will receive 60 mg lomitapide and 2 will receive placebo.	Drug: lomitapide

Outcome Measures

Primary Outcome Measures

Cmax for Lomitapide [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Maximum observed plasma concentration for lomitapide
Tmax for Lomitapide [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Time to maximum observed concentration for lomitapide
AUC0-t for Lomitapide [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for lomitapide
AUC0-∞ for Lomitapide [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Area under the plasma concentration versus time curve from zero to infinity for lomitapide
t1/2 for Lomitapide [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Apparent terminal elimination half-life for lomitapide
Cmax for Lomitapide [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27]
Maximum observed plasma concentration for lomitapide
Tmax for Lomitapide [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27]
Time to maximum observed concentration for lomitapide
AUC0-t for Lomitapide [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27]
Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for lomitapide
t1/2 for Lomitapide [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27]
Apparent terminal elimination half-life for lomitapide

Secondary Outcome Measures

Cmax for M1 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Maximum observed plasma concentration for M1 metabolite of lomitapide
Tmax for M1 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Time to maximum observed concentration for M1 metabolite of lomitapide
AUC0-t for M1 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for M1 metabolite of lomitapide
AUC0-∞ for M1 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Area under the plasma concentration versus time curve from zero to infinity for M1 metabolite of lomitapide
t1/2 for M1 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Apparent terminal elimination half-life for M1 metabolite of lomitapide
Cmax for M3 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Maximum observed plasma concentration for M3 metabolite of lomitapide
Tmax for M3 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Time to maximum observed concentration for M3 metabolite of lomitapide
AUC0-t for M3 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for M3 metabolite of lomitapide
AUC0-∞ for M3 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Area under the plasma concentration versus time curve from zero to infinity for M3 metabolite of lomitapide
t1/2 for M3 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7]
Apparent terminal elimination half-life for M3 metabolite of lomitapide
Cmax for M1 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27]
Maximum observed plasma concentration for M1 metabolite of lomitapide
Tmax for M1 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27]
Time to maximum observed concentration for M1 metabolite of lomitapide
AUC0-t for M1 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27]
Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for M1 metabolite of lomitapide
t1/2 for M1 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27]
Apparent terminal elimination half-life for M1 metabolite of lomitapide
Cmax for M3 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27]
Maximum observed plasma concentration for M3 metabolite of lomitapide
Tmax for M3 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27]
Time to maximum observed concentration for M3 metabolite of lomitapide
AUC0-t for M3 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27]
Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for M3 metabolite of lomitapide
t1/2 for M3 [1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27]
Apparent terminal elimination half-life for M3 metabolite of lomitapide

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Richmond Pharmacology Ltd	Croydon	Surrey	United Kingdom	CR7 7YE

Sponsors and Collaborators

Aegerion Pharmaceuticals, Inc.
Richmond Pharmacology Limited

Investigators

Principal Investigator: Ulrike Lorch, MD FRCA FFPM, Richmond Pharmacology Limited

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Aegerion Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT01760187

Other Study ID Numbers:

AEGR-733-023
2012-004220-37

First Posted:

Jan 4, 2013

Last Update Posted:

Nov 20, 2018

Last Verified:

Nov 1, 2018

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Placebo
Arm/Group Description	10 Japanese and 10 Caucasian subjects will receive 10 mg lomitapide.	6 Japanese and 6 Caucasian subjects will receive 20 mg lomitapide.	6 Japanese and 6 Caucasian subjects will receive 40 mg lomitapide.	6 Japanese and 6 Caucasian subjects will receive 60 mg lomitapide.	8 Japanese and 8 Caucasian subjects will receive placebo.
Period Title: Overall Study
STARTED	20	12	12	12	16
COMPLETED	19	12	12	10	16
NOT COMPLETED	1	0	0	2	0

Baseline Characteristics

Arm/Group Title	Placebo - Japanese Patients	Placebo - Caucasian Patients	Cohort 1- Japanese Patients	Cohort 1 - Caucasian Patients	Cohort 2 - Japanese Patients	Cohort 2 - Caucasian Patients	Cohort 3 - Japanese Patients	Cohort 3 - Caucasian Patients	Cohort 4 - Japanese Patients	Cohort 4 - Caucasian Patients	Total
Arm/Group Description	8 Japanese patients will receive placebo, across the cohorts. (2 at each cohort)	8 Caucasian patients will receive placebo, across the cohorts. (2 at each cohort)	10 Japanese subjects will receive 10 mg of lomitapide.	10 Caucasian subjects will receive 10 mg of lomitapide.	6 Japanese subjects will receive 20 mg of lomitapide.	6 Caucasian subjects will receive 20 mg of lomitapide.	6 Japanese subjects will receive 40 mg of lomitapide.	6 Caucasian subjects will receive 40 mg of lomitapide.	6 Japanese subjects will receive 60 mg of lomitapide.	6 Caucasian subjects will receive 60 mg of lomitapide.	Total of all reporting groups
Overall Participants	8	8	10	10	6	6	6	6	6	6	72
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	8 100%	10 100%	10 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	72 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.1 (6.0)	33.6 (7.3)	33.8 (6.0)	31.2 (6.6)	32.2 (5.4)	36.0 (7.5)	32.5 (4.6)	31.2 (9.7)	30.2 (5.4)	37.7 (3.4)	33.3 (6.2)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	8 100%	8 100%	10 100%	10 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	72 100%
Region of Enrollment (participants) [Number]
United Kingdom	8 100%	8 100%	10 100%	10 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	72 100%

Outcome Measures

1. Primary Outcome

Title	Cmax for Lomitapide
Description	Maximum observed plasma concentration for lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng/mL]	0.570 (0.285)	0.436 (0.166)	1.70 (0.49)	1.01 (0.17)	3.93 (0.75)	3.00 (1.52)	8.29 (3.44)	5.75 (1.78)

2. Primary Outcome

Title	Tmax for Lomitapide
Description	Time to maximum observed concentration for lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Median (Full Range) [hr]	4	5	9	6	4	5	6	5

3. Primary Outcome

Title	AUC0-t for Lomitapide
Description	Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng*hr/mL]	29.1 (13.0)	27.5 (11.0)	63.0 (16.0)	54.2 (9.6)	152 (48)	123 (53)	238 (84)	241 (72)

4. Primary Outcome

Title	AUC0-∞ for Lomitapide
Description	Area under the plasma concentration versus time curve from zero to infinity for lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
AUC0-∞ and t1/2 were not calculated for 3 subjects in the Japanese 10mg arm because the estimated t1/2 was being much longer than half of the total sampling time.

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	7	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng*hr/mL]	37.3 (16.7)	35.9 (15.3)	68.6 (17.4)	64.7 (14.7)	168 (59)	133 (58)	251 (89)	260 (74)

5. Primary Outcome

Title	t1/2 for Lomitapide
Description	Apparent terminal elimination half-life for lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
AUC0-∞ and t1/2 were not calculated for 3 subjects in the Japanese 10mg arm because the estimated t1/2 was being much longer than half of the total sampling time.

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	7	10	6	6	6	6	6	6
Mean (Standard Deviation) [hr]	79.5 (5.6)	82.8 (5.9)	50.5 (2.6)	64.3 (20.6)	58.8 (13.3)	56.2 (7.1)	44.9 (5.7)	51.5 (10.9)

6. Primary Outcome

Title	Cmax for Lomitapide
Description	Maximum observed plasma concentration for lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng/mL]	2.46 (0.88)	3.31 (2.91)	5.96 (2.79)	4.35 (1.07)	19.7 (6.2)	13.8 (5.1)	29.6 (11.1)	24.6 (9.0)

7. Primary Outcome

Title	Tmax for Lomitapide
Description	Time to maximum observed concentration for lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Median (Full Range) [hr]	4	4	4	4	4	4	4	4

8. Primary Outcome

Title	AUC0-t for Lomitapide
Description	Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng*hr/mL]	38.1 (14.1)	44.5 (29.0)	91.3 (29.5)	74.4 (18.8)	263 (64)	204 (79)	388 (86)	403 (130)

9. Primary Outcome

Title	t1/2 for Lomitapide
Description	Apparent terminal elimination half-life for lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [hr]	62.6 (10.1)	57.6 (8.9)	56.1 (9.9)	53.3 (8.5)	49.7 (11.3)	44.8 (6.4)	48.9 (9.9)	46.5 (6.3)

10. Secondary Outcome

Title	Cmax for M1
Description	Maximum observed plasma concentration for M1 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng/mL]	1.23 (0.23)	1.02 (0.23)	2.27 (0.54)	1.86 (0.54)	4.18 (1.22)	4.20 (1.72)	7.43 (1.88)	5.53 (0.83)

11. Secondary Outcome

Title	Tmax for M1
Description	Time to maximum observed concentration for M1 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Median (Full Range) [hr]	6	6	5	6	4	6	6	6

12. Secondary Outcome

Title	AUC0-t for M1
Description	Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for M1 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng*hr/mL]	37.1 (9.7)	32.1 (7.9)	64.1 (15.6)	56.7 (18.6)	134 (37)	129 (57)	199 (64)	177 (44)

13. Secondary Outcome

Title	AUC0-∞ for M1
Description	Area under the plasma concentration versus time curve from zero to infinity for M1 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng*hr/mL]	38.7 (10.1)	34.0 (8.3)	65.7 (15.9)	59.1 (19.5)	138 (39)	132 (58)	204 (67)	183 (46)

14. Secondary Outcome

Title	t1/2 for M1
Description	Apparent terminal elimination half-life for M1 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [hr]	37.8 (11.3)	44.0 (14.3)	35.9 (8.7)	35.9 (6.0)	41.5 (4.3)	36.3 (7.9)	39.4 (3.4)	43.6 (4.9)

15. Secondary Outcome

Title	Cmax for M3
Description	Maximum observed plasma concentration for M3 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng/mL]	20.0 (4.1)	14.2 (4.8)	35.3 (8.2)	20.0 (5.8)	55.7 (18.3)	50.9 (24.7)	83.9 (34.5)	67.7 (23.8)

16. Secondary Outcome

Title	Tmax for M3
Description	Time to maximum observed concentration for M3 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Median (Full Range) [hr]	4	3	4	4	3	2	4	2

17. Secondary Outcome

Title	AUC0-t for M3
Description	Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for M3 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng*hr/mL]	265 (53)	185 (86)	486 (145)	263 (115)	760 (169)	824 (355)	1410 (675)	1170 (541)

18. Secondary Outcome

Title	AUC0-∞ for M3
Description	Area under the plasma concentration versus time curve from zero to infinity for M3 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng*hr/mL]	276 (55)	196 (91.2)	501 (147)	274 (119)	780 (171)	839 (361)	1430 (693)	1200 (551)

19. Secondary Outcome

Title	t1/2 for M3
Description	Apparent terminal elimination half-life for M3 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [hr]	56.3 (11.6)	56.9 (10.2)	53.1 (12.9)	51.3 (6.4)	50.5 (14.9)	39.4 (6.1)	47.0 (7.4)	43.8 (5.3)

20. Secondary Outcome

Title	Cmax for M1
Description	Maximum observed plasma concentration for M1 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng/mL]	2.56 (0.44)	2.15 (0.53)	4.36 (0.88)	4.24 (1.30)	9.98 (4.13)	10.7 (3.6)	13.5 (3.4)	12.6 (3.2)

21. Secondary Outcome

Title	Tmax for M1
Description	Time to maximum observed concentration for M1 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Median (Full Range) [hr]	6	6	6	6	4	6	6	4

22. Secondary Outcome

Title	AUC0-t for M1
Description	Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for M1 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng*hr/mL]	44.3 (8.5)	36.1 (8.5)	73.7 (14.4)	75.3 (25.9)	180 (78)	176 (58)	230 (71)	223 (66)

23. Secondary Outcome

Title	t1/2 for M1
Description	Apparent terminal elimination half-life for M1 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [hr]	42.4 (9.0)	41.9 (7.5)	41.6 (8.5)	39.7 (4.5)	41.0 (6.6)	36.0 (1.7)	43.5 (7.8)	41.2 (6.2)

24. Secondary Outcome

Title	Cmax for M3
Description	Maximum observed plasma concentration for M3 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng/mL]	33.9 (9.3)	24.1 (7.9)	56.4 (15.0)	35.2 (18.8)	76.3 (26.7)	86.4 (27.1)	129 (35)	126 (50)

25. Secondary Outcome

Title	Tmax for M3
Description	Time to maximum observed concentration for M3 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Median (Full Range) [hr]	2	3	3	4	4	4	4	2

26. Secondary Outcome

Title	AUC0-t for M3
Description	Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for M3 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [ng*hr/mL]	335 (84)	239 (90)	617 (163)	386 (183)	891 (259)	1150 (462)	1640 (664)	1640 (767)

27. Secondary Outcome

Title	t1/2 for M3
Description	Apparent terminal elimination half-life for M3 metabolite of lomitapide
Time Frame	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27

Outcome Measure Data

Analysis Population Description
All subjects with evaluable concentrations

Arm/Group Title	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Arm/Group Description	Japanese Subjects who received 10 mg Lomitapide	Caucasian Subjects who received 10 mg Lomitapide	Japanese Subjects who received 20 mg Lomitapide	Caucasian Subjects who received 20 mg Lomitapide	Japanese Subjects who received 40 mg Lomitapide	Caucasian Subjects who received 40 mg Lomitapide	Japanese Subjects who received 60 mg Lomitapide	Caucasian Subjects who received 60 mg Lomitapide
Measure Participants	10	10	6	6	6	6	6	6
Mean (Standard Deviation) [hr]	54.4 (11.0)	44.3 (7.2)	40.4 (6.9)	55.4 (11.5)	41.6 (8.6)	39.3 (7.6)	54.9 (17.4)	41.8 (9.3)

Adverse Events

	Placebo - Japanese Patients		Placebo - Caucasian Patients		Cohort 1- Japanese Patients		Cohort 1 - Caucasian Patients		Cohort 2 - Japanese Patients		Cohort 2 - Caucasian Patients		Cohort 3 - Japanese Patients		Cohort 3 - Caucasian Patients		Cohort 4 - Japanese Patients		Cohort 4 - Caucasian Patients
Time Frame
Adverse Event Reporting Description

Arm/Group Title	Placebo - Japanese Patients		Placebo - Caucasian Patients		Cohort 1- Japanese Patients		Cohort 1 - Caucasian Patients		Cohort 2 - Japanese Patients		Cohort 2 - Caucasian Patients		Cohort 3 - Japanese Patients		Cohort 3 - Caucasian Patients		Cohort 4 - Japanese Patients		Cohort 4 - Caucasian Patients
Arm/Group Description	8 Japanese patients will receive placebo, across the cohorts. (2 at each cohort)		8 Caucasian patients will receive placebo, across the cohorts. (2 at each cohort)		10 Japanese subjects will receive 10 mg of lomitapide.		10 Caucasian subjects will receive 10 mg of lomitapide.		6 Japanese subjects will receive 20 mg of lomitapide.		6 Caucasian subjects will receive 20 mg of lomitapide.		6 Japanese subjects will receive 40 mg of lomitapide.		6 Caucasian subjects will receive 40 mg of lomitapide.		6 Japanese subjects will receive 60 mg of lomitapide.		6 Caucasian subjects will receive 60 mg of lomitapide.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/10 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Placebo - Japanese Patients		Placebo - Caucasian Patients		Cohort 1- Japanese Patients		Cohort 1 - Caucasian Patients		Cohort 2 - Japanese Patients		Cohort 2 - Caucasian Patients		Cohort 3 - Japanese Patients		Cohort 3 - Caucasian Patients		Cohort 4 - Japanese Patients		Cohort 4 - Caucasian Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/10 (0%)		0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Placebo - Japanese Patients		Placebo - Caucasian Patients		Cohort 1- Japanese Patients		Cohort 1 - Caucasian Patients		Cohort 2 - Japanese Patients		Cohort 2 - Caucasian Patients		Cohort 3 - Japanese Patients		Cohort 3 - Caucasian Patients		Cohort 4 - Japanese Patients		Cohort 4 - Caucasian Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		6/8 (75%)		4/10 (40%)		6/10 (60%)		3/6 (50%)		4/6 (66.7%)		5/6 (83.3%)		6/6 (100%)		6/6 (100%)		6/6 (100%)
Gastrointestinal disorders
Abdominal Discomfort	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	2/6 (33.3%)	2	0/6 (0%)	0
Abdominal Distension	1/8 (12.5%)	1	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	4/6 (66.7%)	4	3/6 (50%)	3	5/6 (83.3%)	5
Abdominal Pain	1/8 (12.5%)	1	1/8 (12.5%)	1	1/10 (10%)	1	3/10 (30%)	3	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	2/6 (33.3%)	2
Abdominal Pain Upper	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Change of Bowel Movement	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Constipation	0/8 (0%)	0	1/8 (12.5%)	1	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Diarrhoea	0/8 (0%)	0	1/8 (12.5%)	1	1/10 (10%)	1	1/10 (10%)	1	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	2/6 (33.3%)	2	4/6 (66.7%)	4	3/6 (50%)	3
Dyspepsia	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Mouth Ulceration	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	2/10 (20%)	2	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Nausea	0/8 (0%)	0	0/8 (0%)	0	2/10 (20%)	2	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	1/6 (16.7%)	1	4/6 (66.7%)	4	4/6 (66.7%)	4
Toothache	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Vomiting	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	2/6 (33.3%)	2	1/6 (16.7%)	1
General disorders
Catheter Site Related Reaction	0/8 (0%)	0	1/8 (12.5%)	1	0/10 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Fatigue	0/8 (0%)	0	0/8 (0%)	0	2/10 (20%)	2	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Thirst	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Injury, poisoning and procedural complications
Arthropod Bite	0/8 (0%)	0	0/8 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Investigations
Hepatic Enzyme Increased	0/8 (0%)	0	0/8 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Metabolism and nutrition disorders
Decreased Appetite	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	0/8 (0%)	0	0/8 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Back Pain	0/8 (0%)	0	0/8 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Muscle Spasms	0/8 (0%)	0	1/8 (12.5%)	1	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Pain in Extremity	0/8 (0%)	0	1/8 (12.5%)	1	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Musculoskeletal Chest Pain	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Nervous system disorders
Headache	1/8 (12.5%)	1	0/8 (0%)	0	1/10 (10%)	1	2/10 (20%)	2	1/6 (16.7%)	1	0/6 (0%)	0	2/6 (33.3%)	2	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2
Paraesthesia	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
VIITH Nerve Paralysis	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Psychiatric disorders
Insomnia	0/8 (0%)	0	0/8 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Renal and urinary disorders
Pollakiuria	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/8 (0%)	0	2/8 (25%)	2	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Nasal Congestion	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	3/6 (50%)	3	0/6 (0%)	0	0/6 (0%)	0
Upper Respiratory Tract Infection	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	0/6 (0%)	0	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Vascular disorders
Dizziness	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Epistaxis	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Haematochezia	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Syncope	0/8 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Described in the contract.

Results Point of Contact

Name/Title	Alison Long, MD - VP Clinical
Organization	Aegerion Pharmaceuticals, Inc.
Phone	8572425142
Email	alison.long@aegerion.com

Responsible Party:

Aegerion Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT01760187

Other Study ID Numbers:

AEGR-733-023
2012-004220-37

First Posted:

Jan 4, 2013

Last Update Posted:

Nov 20, 2018

Last Verified:

Nov 1, 2018

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

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

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Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

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Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Study Results

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Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

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