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

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)

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01760187
Enrollment
72
Registered
2013-01-04
Start date
2012-11-07
Completion date
2013-06-03
Last updated
2018-11-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Volunteer

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.

Interventions

DRUGlomitapide

Sponsors

Richmond Pharmacology Limited
CollaboratorINDUSTRY
Aegerion Pharmaceuticals, Inc.
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
20 Years to 45 Years
Healthy volunteers
Yes

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).

Design outcomes

Primary

MeasureTime frameDescription
Cmax for Lomitapide1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Maximum observed plasma concentration for lomitapide
Tmax for Lomitapide1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Time to maximum observed concentration for lomitapide
AUC0-t for Lomitapide1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for lomitapide
AUC0-∞ for Lomitapide1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Area under the plasma concentration versus time curve from zero to infinity for lomitapide
t1/2 for Lomitapide1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Apparent terminal elimination half-life for lomitapide

Secondary

MeasureTime frameDescription
Cmax for M31, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Maximum observed plasma concentration for M3 metabolite of lomitapide
Tmax for M31, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Time to maximum observed concentration for M3 metabolite of lomitapide
Cmax for M11, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Maximum observed plasma concentration for M1 metabolite of lomitapide
AUC0-∞ for M31, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Area under the plasma concentration versus time curve from zero to infinity for M3 metabolite of lomitapide
t1/2 for M31, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Apparent terminal elimination half-life for M3 metabolite of lomitapide
AUC0-t for M31, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for M3 metabolite of lomitapide
Tmax for M11, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Time to maximum observed concentration for M1 metabolite of lomitapide
AUC0-t for M11, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for M1 metabolite of lomitapide
AUC0-∞ for M11, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Area under the plasma concentration versus time curve from zero to infinity for M1 metabolite of lomitapide
t1/2 for M11, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7Apparent terminal elimination half-life for M1 metabolite of lomitapide

Countries

United Kingdom

Participant flow

Participants by arm

ArmCount
Placebo - Japanese Patients
8 Japanese patients will receive placebo, across the cohorts. (2 at each cohort)
8
Placebo - Caucasian Patients
8 Caucasian patients will receive placebo, across the cohorts. (2 at each cohort)
8
Cohort 1- Japanese Patients
10 Japanese subjects will receive 10 mg of lomitapide.
10
Cohort 1 - Caucasian Patients
10 Caucasian subjects will receive 10 mg of lomitapide.
10
Cohort 2 - Japanese Patients
6 Japanese subjects will receive 20 mg of lomitapide.
6
Cohort 2 - Caucasian Patients
6 Caucasian subjects will receive 20 mg of lomitapide.
6
Cohort 3 - Japanese Patients
6 Japanese subjects will receive 40 mg of lomitapide.
6
Cohort 3 - Caucasian Patients
6 Caucasian subjects will receive 40 mg of lomitapide.
6
Cohort 4 - Japanese Patients
6 Japanese subjects will receive 60 mg of lomitapide.
6
Cohort 4 - Caucasian Patients
6 Caucasian subjects will receive 60 mg of lomitapide.
6
Total72

Baseline characteristics

CharacteristicPlacebo - Caucasian PatientsCohort 1- Japanese PatientsCohort 1 - Caucasian PatientsCohort 2 - Japanese PatientsCohort 2 - Caucasian PatientsPlacebo - Japanese PatientsCohort 3 - Japanese PatientsCohort 3 - Caucasian PatientsCohort 4 - Japanese PatientsCohort 4 - Caucasian PatientsTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
8 Participants10 Participants10 Participants6 Participants6 Participants8 Participants6 Participants6 Participants6 Participants6 Participants72 Participants
Age, Continuous33.6 years
STANDARD_DEVIATION 7.3
33.8 years
STANDARD_DEVIATION 6
31.2 years
STANDARD_DEVIATION 6.6
32.2 years
STANDARD_DEVIATION 5.4
36.0 years
STANDARD_DEVIATION 7.5
34.1 years
STANDARD_DEVIATION 6
32.5 years
STANDARD_DEVIATION 4.6
31.2 years
STANDARD_DEVIATION 9.7
30.2 years
STANDARD_DEVIATION 5.4
37.7 years
STANDARD_DEVIATION 3.4
33.3 years
STANDARD_DEVIATION 6.2
Region of Enrollment
United Kingdom
8 participants10 participants10 participants6 participants6 participants8 participants6 participants6 participants6 participants6 participants72 participants
Sex: Female, Male
Female
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Sex: Female, Male
Male
8 Participants10 Participants10 Participants6 Participants6 Participants8 Participants6 Participants6 Participants6 Participants6 Participants72 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
EG007
affected / at risk
EG008
affected / at risk
EG009
affected / at risk
deaths
Total, all-cause mortality
0 / 80 / 80 / 100 / 100 / 60 / 60 / 60 / 60 / 60 / 6
other
Total, other adverse events
2 / 86 / 84 / 106 / 103 / 64 / 65 / 66 / 66 / 66 / 6
serious
Total, serious adverse events
0 / 80 / 80 / 100 / 100 / 60 / 60 / 60 / 60 / 60 / 6

Outcome results

Primary

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

Population: 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.

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgAUC0-∞ for Lomitapide37.3 ng*hr/mLStandard Deviation 16.7
Caucasian 10 mgAUC0-∞ for Lomitapide35.9 ng*hr/mLStandard Deviation 15.3
Japanese 20 mgAUC0-∞ for Lomitapide68.6 ng*hr/mLStandard Deviation 17.4
Caucasian 20 mgAUC0-∞ for Lomitapide64.7 ng*hr/mLStandard Deviation 14.7
Japanese 40 mgAUC0-∞ for Lomitapide168 ng*hr/mLStandard Deviation 59
Caucasian 40 mgAUC0-∞ for Lomitapide133 ng*hr/mLStandard Deviation 58
Japanese 60 mgAUC0-∞ for Lomitapide251 ng*hr/mLStandard Deviation 89
Caucasian 60 mgAUC0-∞ for Lomitapide260 ng*hr/mLStandard Deviation 74
Primary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgAUC0-t for Lomitapide29.1 ng*hr/mLStandard Deviation 13
Caucasian 10 mgAUC0-t for Lomitapide27.5 ng*hr/mLStandard Deviation 11
Japanese 20 mgAUC0-t for Lomitapide63.0 ng*hr/mLStandard Deviation 16
Caucasian 20 mgAUC0-t for Lomitapide54.2 ng*hr/mLStandard Deviation 9.6
Japanese 40 mgAUC0-t for Lomitapide152 ng*hr/mLStandard Deviation 48
Caucasian 40 mgAUC0-t for Lomitapide123 ng*hr/mLStandard Deviation 53
Japanese 60 mgAUC0-t for Lomitapide238 ng*hr/mLStandard Deviation 84
Caucasian 60 mgAUC0-t for Lomitapide241 ng*hr/mLStandard Deviation 72
Primary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgAUC0-t for Lomitapide38.1 ng*hr/mLStandard Deviation 14.1
Caucasian 10 mgAUC0-t for Lomitapide44.5 ng*hr/mLStandard Deviation 29
Japanese 20 mgAUC0-t for Lomitapide91.3 ng*hr/mLStandard Deviation 29.5
Caucasian 20 mgAUC0-t for Lomitapide74.4 ng*hr/mLStandard Deviation 18.8
Japanese 40 mgAUC0-t for Lomitapide263 ng*hr/mLStandard Deviation 64
Caucasian 40 mgAUC0-t for Lomitapide204 ng*hr/mLStandard Deviation 79
Japanese 60 mgAUC0-t for Lomitapide388 ng*hr/mLStandard Deviation 86
Caucasian 60 mgAUC0-t for Lomitapide403 ng*hr/mLStandard Deviation 130
Primary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgCmax for Lomitapide0.570 ng/mLStandard Deviation 0.285
Caucasian 10 mgCmax for Lomitapide0.436 ng/mLStandard Deviation 0.166
Japanese 20 mgCmax for Lomitapide1.70 ng/mLStandard Deviation 0.49
Caucasian 20 mgCmax for Lomitapide1.01 ng/mLStandard Deviation 0.17
Japanese 40 mgCmax for Lomitapide3.93 ng/mLStandard Deviation 0.75
Caucasian 40 mgCmax for Lomitapide3.00 ng/mLStandard Deviation 1.52
Japanese 60 mgCmax for Lomitapide8.29 ng/mLStandard Deviation 3.44
Caucasian 60 mgCmax for Lomitapide5.75 ng/mLStandard Deviation 1.78
Primary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgCmax for Lomitapide2.46 ng/mLStandard Deviation 0.88
Caucasian 10 mgCmax for Lomitapide3.31 ng/mLStandard Deviation 2.91
Japanese 20 mgCmax for Lomitapide5.96 ng/mLStandard Deviation 2.79
Caucasian 20 mgCmax for Lomitapide4.35 ng/mLStandard Deviation 1.07
Japanese 40 mgCmax for Lomitapide19.7 ng/mLStandard Deviation 6.2
Caucasian 40 mgCmax for Lomitapide13.8 ng/mLStandard Deviation 5.1
Japanese 60 mgCmax for Lomitapide29.6 ng/mLStandard Deviation 11.1
Caucasian 60 mgCmax for Lomitapide24.6 ng/mLStandard Deviation 9
Primary

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

Population: 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.

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgt1/2 for Lomitapide79.5 hrStandard Deviation 5.6
Caucasian 10 mgt1/2 for Lomitapide82.8 hrStandard Deviation 5.9
Japanese 20 mgt1/2 for Lomitapide50.5 hrStandard Deviation 2.6
Caucasian 20 mgt1/2 for Lomitapide64.3 hrStandard Deviation 20.6
Japanese 40 mgt1/2 for Lomitapide58.8 hrStandard Deviation 13.3
Caucasian 40 mgt1/2 for Lomitapide56.2 hrStandard Deviation 7.1
Japanese 60 mgt1/2 for Lomitapide44.9 hrStandard Deviation 5.7
Caucasian 60 mgt1/2 for Lomitapide51.5 hrStandard Deviation 10.9
Primary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgt1/2 for Lomitapide62.6 hrStandard Deviation 10.1
Caucasian 10 mgt1/2 for Lomitapide57.6 hrStandard Deviation 8.9
Japanese 20 mgt1/2 for Lomitapide56.1 hrStandard Deviation 9.9
Caucasian 20 mgt1/2 for Lomitapide53.3 hrStandard Deviation 8.5
Japanese 40 mgt1/2 for Lomitapide49.7 hrStandard Deviation 11.3
Caucasian 40 mgt1/2 for Lomitapide44.8 hrStandard Deviation 6.4
Japanese 60 mgt1/2 for Lomitapide48.9 hrStandard Deviation 9.9
Caucasian 60 mgt1/2 for Lomitapide46.5 hrStandard Deviation 6.3
Primary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEDIAN)
Japanese 10 mgTmax for Lomitapide4 hr
Caucasian 10 mgTmax for Lomitapide4 hr
Japanese 20 mgTmax for Lomitapide4 hr
Caucasian 20 mgTmax for Lomitapide4 hr
Japanese 40 mgTmax for Lomitapide4 hr
Caucasian 40 mgTmax for Lomitapide4 hr
Japanese 60 mgTmax for Lomitapide4 hr
Caucasian 60 mgTmax for Lomitapide4 hr
Primary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEDIAN)
Japanese 10 mgTmax for Lomitapide4 hr
Caucasian 10 mgTmax for Lomitapide5 hr
Japanese 20 mgTmax for Lomitapide9 hr
Caucasian 20 mgTmax for Lomitapide6 hr
Japanese 40 mgTmax for Lomitapide4 hr
Caucasian 40 mgTmax for Lomitapide5 hr
Japanese 60 mgTmax for Lomitapide6 hr
Caucasian 60 mgTmax for Lomitapide5 hr
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgAUC0-∞ for M138.7 ng*hr/mLStandard Deviation 10.1
Caucasian 10 mgAUC0-∞ for M134.0 ng*hr/mLStandard Deviation 8.3
Japanese 20 mgAUC0-∞ for M165.7 ng*hr/mLStandard Deviation 15.9
Caucasian 20 mgAUC0-∞ for M159.1 ng*hr/mLStandard Deviation 19.5
Japanese 40 mgAUC0-∞ for M1138 ng*hr/mLStandard Deviation 39
Caucasian 40 mgAUC0-∞ for M1132 ng*hr/mLStandard Deviation 58
Japanese 60 mgAUC0-∞ for M1204 ng*hr/mLStandard Deviation 67
Caucasian 60 mgAUC0-∞ for M1183 ng*hr/mLStandard Deviation 46
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgAUC0-∞ for M3276 ng*hr/mLStandard Deviation 55
Caucasian 10 mgAUC0-∞ for M3196 ng*hr/mLStandard Deviation 91.2
Japanese 20 mgAUC0-∞ for M3501 ng*hr/mLStandard Deviation 147
Caucasian 20 mgAUC0-∞ for M3274 ng*hr/mLStandard Deviation 119
Japanese 40 mgAUC0-∞ for M3780 ng*hr/mLStandard Deviation 171
Caucasian 40 mgAUC0-∞ for M3839 ng*hr/mLStandard Deviation 361
Japanese 60 mgAUC0-∞ for M31430 ng*hr/mLStandard Deviation 693
Caucasian 60 mgAUC0-∞ for M31200 ng*hr/mLStandard Deviation 551
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgAUC0-t for M137.1 ng*hr/mLStandard Deviation 9.7
Caucasian 10 mgAUC0-t for M132.1 ng*hr/mLStandard Deviation 7.9
Japanese 20 mgAUC0-t for M164.1 ng*hr/mLStandard Deviation 15.6
Caucasian 20 mgAUC0-t for M156.7 ng*hr/mLStandard Deviation 18.6
Japanese 40 mgAUC0-t for M1134 ng*hr/mLStandard Deviation 37
Caucasian 40 mgAUC0-t for M1129 ng*hr/mLStandard Deviation 57
Japanese 60 mgAUC0-t for M1199 ng*hr/mLStandard Deviation 64
Caucasian 60 mgAUC0-t for M1177 ng*hr/mLStandard Deviation 44
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgAUC0-t for M144.3 ng*hr/mLStandard Deviation 8.5
Caucasian 10 mgAUC0-t for M136.1 ng*hr/mLStandard Deviation 8.5
Japanese 20 mgAUC0-t for M173.7 ng*hr/mLStandard Deviation 14.4
Caucasian 20 mgAUC0-t for M175.3 ng*hr/mLStandard Deviation 25.9
Japanese 40 mgAUC0-t for M1180 ng*hr/mLStandard Deviation 78
Caucasian 40 mgAUC0-t for M1176 ng*hr/mLStandard Deviation 58
Japanese 60 mgAUC0-t for M1230 ng*hr/mLStandard Deviation 71
Caucasian 60 mgAUC0-t for M1223 ng*hr/mLStandard Deviation 66
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgAUC0-t for M3335 ng*hr/mLStandard Deviation 84
Caucasian 10 mgAUC0-t for M3239 ng*hr/mLStandard Deviation 90
Japanese 20 mgAUC0-t for M3617 ng*hr/mLStandard Deviation 163
Caucasian 20 mgAUC0-t for M3386 ng*hr/mLStandard Deviation 183
Japanese 40 mgAUC0-t for M3891 ng*hr/mLStandard Deviation 259
Caucasian 40 mgAUC0-t for M31150 ng*hr/mLStandard Deviation 462
Japanese 60 mgAUC0-t for M31640 ng*hr/mLStandard Deviation 664
Caucasian 60 mgAUC0-t for M31640 ng*hr/mLStandard Deviation 767
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgAUC0-t for M3265 ng*hr/mLStandard Deviation 53
Caucasian 10 mgAUC0-t for M3185 ng*hr/mLStandard Deviation 86
Japanese 20 mgAUC0-t for M3486 ng*hr/mLStandard Deviation 145
Caucasian 20 mgAUC0-t for M3263 ng*hr/mLStandard Deviation 115
Japanese 40 mgAUC0-t for M3760 ng*hr/mLStandard Deviation 169
Caucasian 40 mgAUC0-t for M3824 ng*hr/mLStandard Deviation 355
Japanese 60 mgAUC0-t for M31410 ng*hr/mLStandard Deviation 675
Caucasian 60 mgAUC0-t for M31170 ng*hr/mLStandard Deviation 541
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgCmax for M11.23 ng/mLStandard Deviation 0.23
Caucasian 10 mgCmax for M11.02 ng/mLStandard Deviation 0.23
Japanese 20 mgCmax for M12.27 ng/mLStandard Deviation 0.54
Caucasian 20 mgCmax for M11.86 ng/mLStandard Deviation 0.54
Japanese 40 mgCmax for M14.18 ng/mLStandard Deviation 1.22
Caucasian 40 mgCmax for M14.20 ng/mLStandard Deviation 1.72
Japanese 60 mgCmax for M17.43 ng/mLStandard Deviation 1.88
Caucasian 60 mgCmax for M15.53 ng/mLStandard Deviation 0.83
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgCmax for M12.56 ng/mLStandard Deviation 0.44
Caucasian 10 mgCmax for M12.15 ng/mLStandard Deviation 0.53
Japanese 20 mgCmax for M14.36 ng/mLStandard Deviation 0.88
Caucasian 20 mgCmax for M14.24 ng/mLStandard Deviation 1.3
Japanese 40 mgCmax for M19.98 ng/mLStandard Deviation 4.13
Caucasian 40 mgCmax for M110.7 ng/mLStandard Deviation 3.6
Japanese 60 mgCmax for M113.5 ng/mLStandard Deviation 3.4
Caucasian 60 mgCmax for M112.6 ng/mLStandard Deviation 3.2
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgCmax for M333.9 ng/mLStandard Deviation 9.3
Caucasian 10 mgCmax for M324.1 ng/mLStandard Deviation 7.9
Japanese 20 mgCmax for M356.4 ng/mLStandard Deviation 15
Caucasian 20 mgCmax for M335.2 ng/mLStandard Deviation 18.8
Japanese 40 mgCmax for M376.3 ng/mLStandard Deviation 26.7
Caucasian 40 mgCmax for M386.4 ng/mLStandard Deviation 27.1
Japanese 60 mgCmax for M3129 ng/mLStandard Deviation 35
Caucasian 60 mgCmax for M3126 ng/mLStandard Deviation 50
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgCmax for M320.0 ng/mLStandard Deviation 4.1
Caucasian 10 mgCmax for M314.2 ng/mLStandard Deviation 4.8
Japanese 20 mgCmax for M335.3 ng/mLStandard Deviation 8.2
Caucasian 20 mgCmax for M320.0 ng/mLStandard Deviation 5.8
Japanese 40 mgCmax for M355.7 ng/mLStandard Deviation 18.3
Caucasian 40 mgCmax for M350.9 ng/mLStandard Deviation 24.7
Japanese 60 mgCmax for M383.9 ng/mLStandard Deviation 34.5
Caucasian 60 mgCmax for M367.7 ng/mLStandard Deviation 23.8
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgt1/2 for M137.8 hrStandard Deviation 11.3
Caucasian 10 mgt1/2 for M144.0 hrStandard Deviation 14.3
Japanese 20 mgt1/2 for M135.9 hrStandard Deviation 8.7
Caucasian 20 mgt1/2 for M135.9 hrStandard Deviation 6
Japanese 40 mgt1/2 for M141.5 hrStandard Deviation 4.3
Caucasian 40 mgt1/2 for M136.3 hrStandard Deviation 7.9
Japanese 60 mgt1/2 for M139.4 hrStandard Deviation 3.4
Caucasian 60 mgt1/2 for M143.6 hrStandard Deviation 4.9
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgt1/2 for M142.4 hrStandard Deviation 9
Caucasian 10 mgt1/2 for M141.9 hrStandard Deviation 7.5
Japanese 20 mgt1/2 for M141.6 hrStandard Deviation 8.5
Caucasian 20 mgt1/2 for M139.7 hrStandard Deviation 4.5
Japanese 40 mgt1/2 for M141.0 hrStandard Deviation 6.6
Caucasian 40 mgt1/2 for M136.0 hrStandard Deviation 1.7
Japanese 60 mgt1/2 for M143.5 hrStandard Deviation 7.8
Caucasian 60 mgt1/2 for M141.2 hrStandard Deviation 6.2
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgt1/2 for M356.3 hrStandard Deviation 11.6
Caucasian 10 mgt1/2 for M356.9 hrStandard Deviation 10.2
Japanese 20 mgt1/2 for M353.1 hrStandard Deviation 12.9
Caucasian 20 mgt1/2 for M351.3 hrStandard Deviation 6.4
Japanese 40 mgt1/2 for M350.5 hrStandard Deviation 14.9
Caucasian 40 mgt1/2 for M339.4 hrStandard Deviation 6.1
Japanese 60 mgt1/2 for M347.0 hrStandard Deviation 7.4
Caucasian 60 mgt1/2 for M343.8 hrStandard Deviation 5.3
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEAN)Dispersion
Japanese 10 mgt1/2 for M354.4 hrStandard Deviation 11
Caucasian 10 mgt1/2 for M344.3 hrStandard Deviation 7.2
Japanese 20 mgt1/2 for M340.4 hrStandard Deviation 6.9
Caucasian 20 mgt1/2 for M355.4 hrStandard Deviation 11.5
Japanese 40 mgt1/2 for M341.6 hrStandard Deviation 8.6
Caucasian 40 mgt1/2 for M339.3 hrStandard Deviation 7.6
Japanese 60 mgt1/2 for M354.9 hrStandard Deviation 17.4
Caucasian 60 mgt1/2 for M341.8 hrStandard Deviation 9.3
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEDIAN)
Japanese 10 mgTmax for M16 hr
Caucasian 10 mgTmax for M16 hr
Japanese 20 mgTmax for M15 hr
Caucasian 20 mgTmax for M16 hr
Japanese 40 mgTmax for M14 hr
Caucasian 40 mgTmax for M16 hr
Japanese 60 mgTmax for M16 hr
Caucasian 60 mgTmax for M16 hr
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEDIAN)
Japanese 10 mgTmax for M16 hr
Caucasian 10 mgTmax for M16 hr
Japanese 20 mgTmax for M16 hr
Caucasian 20 mgTmax for M16 hr
Japanese 40 mgTmax for M14 hr
Caucasian 40 mgTmax for M16 hr
Japanese 60 mgTmax for M16 hr
Caucasian 60 mgTmax for M14 hr
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEDIAN)
Japanese 10 mgTmax for M34 hr
Caucasian 10 mgTmax for M33 hr
Japanese 20 mgTmax for M34 hr
Caucasian 20 mgTmax for M34 hr
Japanese 40 mgTmax for M33 hr
Caucasian 40 mgTmax for M32 hr
Japanese 60 mgTmax for M34 hr
Caucasian 60 mgTmax for M32 hr
Secondary

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

Population: All subjects with evaluable concentrations

ArmMeasureValue (MEDIAN)
Japanese 10 mgTmax for M32 hr
Caucasian 10 mgTmax for M33 hr
Japanese 20 mgTmax for M33 hr
Caucasian 20 mgTmax for M34 hr
Japanese 40 mgTmax for M34 hr
Caucasian 40 mgTmax for M34 hr
Japanese 60 mgTmax for M34 hr
Caucasian 60 mgTmax for M32 hr

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026