Phase I Study of the Safety, Tolerability, PK & PD of Lom... | NCT01760187

NCT01760187

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2012-004220-37	EudraCT Number

Status Module

Name	Class
Richmond Pharmacology Limited	INDUSTRY

Arms/Interventions Module

Arm Groups

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

Name	Type	Description	Arm Group Labels	Other Names
lomitapide	Drug		Cohort 1 Cohort 2 Cohort 3 Cohort 4

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

Measure	Description	Time Frame
Cmax for M1	Maximum observed plasma concentration for M1 metabolite of lomitapide	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

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

1. Subject is a healthy male or female, Caucasian or Japanese, aged 20 - 45 years, inclusive, at screening.

2. Subject has a BMI of 18.5 - 30 kg/m2 inclusive at screening.

3. Subjects must have a screening LDL-C measurement and the mean of Day 5 and Day 6 measurements greater than or equal to 110mg/dL.

4. Subjects must agree to use acceptable methods of contraception (details provided in the protocol)

5. Subjects must be capable of understanding and complying with the requirements of the protocol and must have signed the informed consent form prior to undergoing any study-related procedures.

Exclusion Criteria:

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).

Name	Affiliation	Role
Ulrike Lorch, MD FRCA FFPM	Richmond Pharmacology Limited	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Richmond Pharmacology Ltd		Croydon	Surrey	CR7 7YE	United Kingdom

ID	Title	Description
FG000	Cohort 1	10 Japanese and 10 Caucasian subjects will receive 10 mg lomitapide.
FG001	Cohort 2	6 Japanese and 6 Caucasian subjects will receive 20 mg lomitapide.
FG002	Cohort 3	6 Japanese and 6 Caucasian subjects will receive 40 mg lomitapide.
FG003	Cohort 4	6 Japanese and 6 Caucasian subjects will receive 60 mg lomitapide.
FG004	Placebo	8 Japanese and 8 Caucasian subjects will receive placebo.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Placebo - Japanese Patients	8 Japanese patients will receive placebo, across the cohorts. (2 at each cohort)
BG001	Placebo - Caucasian Patients	8 Caucasian patients will receive placebo, across the cohorts. (2 at each cohort)

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Cmax for Lomitapide

Maximum observed plasma concentration for lomitapide

All subjects with evaluable concentrations

Posted

Mean

Standard Deviation

ng/mL

1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7

ID	Title	Description
OG000	Japanese 10 mg	Japanese Subjects who received 10 mg Lomitapide
OG001	Caucasian 10 mg	Caucasian Subjects who received 10 mg Lomitapide
OG002	Japanese 20 mg

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo - Japanese Patients	8 Japanese patients will receive placebo, across the cohorts. (2 at each cohort)