CompletedNCT01760187Updated Nov 20, 2018Results posted

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

A Phase 1 interventional study of lomitapide in Healthy Volunteer, sponsored by Aegerion Pharmaceuticals, Inc.. Completed at 1 site in United Kingdom. Open to participants aged 20 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-11-20.

Sponsored by Aegerion Pharmaceuticals, Inc. · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 72
Allocation: Randomized
Ages: 20 Years to 45 Years
Sex: All

Study 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.

Conditions studied

Healthy Volunteer

Who can participate

Ages eligible: 20 Years to 45 Years
Sexes eligible: 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.
  1. Subject has a BMI of 18.5 - 30 kg/m2 inclusive at screening.
  1. 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.
  1. Subjects must agree to use acceptable methods of contraception (details provided in the protocol)
  1. 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

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).

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 72 participants (actual)

Study arms

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

Interventions

Druglomitapide

What researchers measure

Primary outcomes

Cmax for Lomitapide
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
Tmax for Lomitapide
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
AUC0-t for Lomitapide
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
AUC0-∞ for Lomitapide
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
t1/2 for Lomitapide
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
Cmax for Lomitapide
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
Tmax for Lomitapide
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
AUC0-t for Lomitapide
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
t1/2 for Lomitapide
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

Secondary outcomes

Cmax for M1
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
Tmax for M1
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
AUC0-t for M1
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
AUC0-∞ for M1
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
t1/2 for M1
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
Cmax for M3
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
Tmax for M3
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
AUC0-t for M3
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
AUC0-∞ for M3
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
t1/2 for M3
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
Cmax for M1
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
Tmax for M1
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
AUC0-t for M1
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
t1/2 for M1
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
Cmax for M3
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
Tmax for M3
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
AUC0-t for M3
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
t1/2 for M3
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

Results

Posted Nov 20, 2018

Participant flow

Participant flow — Overall Study
Milestone	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Placebo
Started	20	12	12	12	16
Completed	19	12	12	10	16
Not completed	1	0	0	2	0

Outcome measures

PrimaryCmax for Lomitapide

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
Reported as:: Mean · ng/mL

Cmax for Lomitapide
ng/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Cmax for Lomitapide	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

PrimaryTmax for Lomitapide

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
Reported as:: Median · hr

Tmax for Lomitapide
hr	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Tmax for Lomitapide	4 (2 to 6)	5 (2 to 12)	9 (4 to 12)	6 (2 to 12)	4 (2 to 6)	5 (4 to 8)	6 (4 to 6)	5 (2 to 6)

PrimaryAUC0-t for Lomitapide

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
Reported as:: Mean · ng*hr/mL

AUC0-t for Lomitapide
ng*hr/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
AUC0-t for Lomitapide	29.1 ± 13.0	27.5 ± 11.0	63.0 ± 16.0	54.2 ± 9.6	152 ± 48	123 ± 53	238 ± 84	241 ± 72

PrimaryAUC0-∞ for Lomitapide

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
Reported as:: Mean · ng*hr/mL

AUC0-∞ for Lomitapide
ng*hr/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
AUC0-∞ for Lomitapide	37.3 ± 16.7	35.9 ± 15.3	68.6 ± 17.4	64.7 ± 14.7	168 ± 59	133 ± 58	251 ± 89	260 ± 74

Primaryt1/2 for Lomitapide

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
Reported as:: Mean · hr

t1/2 for Lomitapide
hr	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
t1/2 for Lomitapide	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

PrimaryCmax for Lomitapide

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
Reported as:: Mean · ng/mL

Cmax for Lomitapide
ng/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Cmax for Lomitapide	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

PrimaryTmax for Lomitapide

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
Reported as:: Median · hr

Tmax for Lomitapide
hr	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Tmax for Lomitapide	4 (1 to 4)	4 (2 to 6)	4 (1 to 8)	4 (4 to 4)	4 (4 to 4)	4 (4 to 6)	4 (2 to 6)	4 (2 to 4)

PrimaryAUC0-t for Lomitapide

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
Reported as:: Mean · ng*hr/mL

AUC0-t for Lomitapide
ng*hr/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
AUC0-t for Lomitapide	38.1 ± 14.1	44.5 ± 29.0	91.3 ± 29.5	74.4 ± 18.8	263 ± 64	204 ± 79	388 ± 86	403 ± 130

Primaryt1/2 for Lomitapide

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
Reported as:: Mean · hr

t1/2 for Lomitapide
hr	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
t1/2 for Lomitapide	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

SecondaryCmax for M1

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
Reported as:: Mean · ng/mL

Cmax for M1
ng/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Cmax for M1	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

SecondaryTmax for M1

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
Reported as:: Median · hr

Tmax for M1
hr	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Tmax for M1	6 (4 to 8)	6 (4 to 6)	5 (4 to 6)	6 (4 to 8)	4 (1 to 8)	6 (4 to 8)	6 (4 to 6)	6 (2 to 8)

SecondaryAUC0-t for M1

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
Reported as:: Mean · ng*hr/mL

AUC0-t for M1
ng*hr/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
AUC0-t for M1	37.1 ± 9.7	32.1 ± 7.9	64.1 ± 15.6	56.7 ± 18.6	134 ± 37	129 ± 57	199 ± 64	177 ± 44

SecondaryAUC0-∞ for M1

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
Reported as:: Mean · ng*hr/mL

AUC0-∞ for M1
ng*hr/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
AUC0-∞ for M1	38.7 ± 10.1	34.0 ± 8.3	65.7 ± 15.9	59.1 ± 19.5	138 ± 39	132 ± 58	204 ± 67	183 ± 46

Secondaryt1/2 for M1

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
Reported as:: Mean · hr

t1/2 for M1
hr	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
t1/2 for M1	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

SecondaryCmax for M3

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
Reported as:: Mean · ng/mL

Cmax for M3
ng/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Cmax for M3	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

SecondaryTmax for M3

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
Reported as:: Median · hr

Tmax for M3
hr	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Tmax for M3	4 (2 to 4)	3 (2 to 4)	4 (2 to 4)	4 (2 to 4)	3 (1 to 4)	2 (2 to 4)	4 (4 to 4)	2 (1 to 4)

SecondaryAUC0-t for M3

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
Reported as:: Mean · ng*hr/mL

AUC0-t for M3
ng*hr/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
AUC0-t for M3	265 ± 53	185 ± 86	486 ± 145	263 ± 115	760 ± 169	824 ± 355	1410 ± 675	1170 ± 541

SecondaryAUC0-∞ for M3

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
Reported as:: Mean · ng*hr/mL

AUC0-∞ for M3
ng*hr/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
AUC0-∞ for M3	276 ± 55	196 ± 91.2	501 ± 147	274 ± 119	780 ± 171	839 ± 361	1430 ± 693	1200 ± 551

Secondaryt1/2 for M3

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
Reported as:: Mean · hr

t1/2 for M3
hr	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
t1/2 for M3	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

SecondaryCmax for M1

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
Reported as:: Mean · ng/mL

Cmax for M1
ng/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Cmax for M1	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

SecondaryTmax for M1

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
Reported as:: Median · hr

Tmax for M1
hr	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Tmax for M1	6 (2 to 8)	6 (2 to 6)	6 (4 to 6)	6 (4 to 8)	4 (4 to 8)	6 (4 to 6)	6 (4 to 8)	4 (4 to 8)

SecondaryAUC0-t for M1

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
Reported as:: Mean · ng*hr/mL

AUC0-t for M1
ng*hr/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
AUC0-t for M1	44.3 ± 8.5	36.1 ± 8.5	73.7 ± 14.4	75.3 ± 25.9	180 ± 78	176 ± 58	230 ± 71	223 ± 66

Secondaryt1/2 for M1

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
Reported as:: Mean · hr

t1/2 for M1
hr	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
t1/2 for M1	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

SecondaryCmax for M3

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
Reported as:: Mean · ng/mL

Cmax for M3
ng/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Cmax for M3	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

SecondaryTmax for M3

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
Reported as:: Median · hr

Tmax for M3
hr	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
Tmax for M3	2 (2 to 4)	3 (2 to 6)	3 (2 to 4)	4 (2 to 4)	4 (2 to 4)	4 (2 to 6)	4 (2 to 6)	2 (2 to 4)

SecondaryAUC0-t for M3

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
Reported as:: Mean · ng*hr/mL

AUC0-t for M3
ng*hr/mL	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
AUC0-t for M3	335 ± 84	239 ± 90	617 ± 163	386 ± 183	891 ± 259	1150 ± 462	1640 ± 664	1640 ± 767

Secondaryt1/2 for M3

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
Reported as:: Mean · hr

t1/2 for M3
hr	Japanese 10 mg	Caucasian 10 mg	Japanese 20 mg	Caucasian 20 mg	Japanese 40 mg	Caucasian 40 mg	Japanese 60 mg	Caucasian 60 mg
t1/2 for M3	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

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo - Japanese Patients	0/8 (0%)	0/8 (0%)	2/8 (25%)
Placebo - Caucasian Patients	0/8 (0%)	0/8 (0%)	6/8 (75%)
Cohort 1- Japanese Patients	0/10 (0%)	0/10 (0%)	4/10 (40%)
Cohort 1 - Caucasian Patients	0/10 (0%)	0/10 (0%)	6/10 (60%)
Cohort 2 - Japanese Patients	0/6 (0%)	0/6 (0%)	3/6 (50%)
Cohort 2 - Caucasian Patients	0/6 (0%)	0/6 (0%)	4/6 (66.7%)
Cohort 3 - Japanese Patients	0/6 (0%)	0/6 (0%)	5/6 (83.3%)
Cohort 3 - Caucasian Patients	0/6 (0%)	0/6 (0%)	6/6 (100%)
Cohort 4 - Japanese Patients	0/6 (0%)	0/6 (0%)	6/6 (100%)
Cohort 4 - Caucasian Patients	0/6 (0%)	0/6 (0%)	6/6 (100%)

Most frequent other events

Showing 10 of 36

Most frequent other events
Event	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
Abdominal DistensionGastrointestinal disorders	1/8	0/8	0/10	0/10	0/6	0/6	2/6	4/6	3/6	5/6
DiarrhoeaGastrointestinal disorders	0/8	1/8	1/10	1/10	0/6	0/6	1/6	2/6	4/6	3/6
NauseaGastrointestinal disorders	0/8	0/8	2/10	0/10	0/6	0/6	2/6	1/6	4/6	4/6
Nasal CongestionRespiratory, thoracic and mediastinal disorders	0/8	0/8	0/10	0/10	0/6	0/6	0/6	3/6	0/6	0/6
Abdominal DiscomfortGastrointestinal disorders	0/8	0/8	0/10	0/10	0/6	1/6	1/6	0/6	2/6	0/6
Abdominal PainGastrointestinal disorders	1/8	1/8	1/10	3/10	0/6	0/6	0/6	1/6	1/6	2/6
VomitingGastrointestinal disorders	0/8	0/8	0/10	0/10	0/6	0/6	1/6	1/6	2/6	1/6
Decreased AppetiteMetabolism and nutrition disorders	0/8	0/8	0/10	1/10	0/6	0/6	0/6	0/6	0/6	2/6
HeadacheNervous system disorders	1/8	0/8	1/10	2/10	1/6	0/6	2/6	0/6	0/6	2/6
Upper Respiratory Tract InfectionRespiratory, thoracic and mediastinal disorders	0/8	0/8	0/10	1/10	0/6	0/6	0/6	2/6	0/6	0/6

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	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
<=18 years	0	0	0	0	0	0	0	0	0	0	0
Between 18 and 65 years	8	8	10	10	6	6	6	6	6	6	72
>=65 years	0	0	0	0	0	0	0	0	0	0	0

Age, Continuous
Age, Continuous(years)	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
Mean	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
Sex: Female, Male(Participants)	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
Female	0	0	0	0	0	0	0	0	0	0	0
Male	8	8	10	10	6	6	6	6	6	6	72

Region of Enrollment
Region of Enrollment(participants)	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
United Kingdom	8	8	10	10	6	6	6	6	6	6	72

Study locations

1 site

Richmond Pharmacology Ltd
Croydon, Surrey CR7 7YE, United Kingdom

Registry details

Key details

Study ID: NCT01760187
Lead sponsor: Aegerion Pharmaceuticals, Inc.
Collaborators: Richmond Pharmacology Limited
Responsible party: Sponsor
First posted: Jan 4, 2013
Start date: Nov 7, 2012
Primary completion: Jun 3, 2013
Completion: Jun 3, 2013
Results posted: Nov 20, 2018
Last update: Nov 20, 2018

Study contacts

Ulrike Lorch, MD FRCA FFPM

principal investigator · Richmond Pharmacology Limited

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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