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

This study has been completed.
Sponsor:
Collaborator:
Richmond Pharmacology Limited
Information provided by (Responsible Party):
Aegerion Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01760187
First received: November 21, 2012
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Healthy Volunteer
Drug: lomitapide
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by Aegerion Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Pharmacokinetics (PK) comparison [ Time Frame: Pharmacokinetic samples will be taken pre-dose on Day 1 up to Day 27 post treatment. ] [ Designated as safety issue: No ]
    To compare the pharmacokinetics (PK) of lomitapide between Japanese and Caucasian subjects with elevated LDL-C after single and multiple doses, across the dose range studied.


Secondary Outcome Measures:
  • To evaluate the number of adverse events and changes in laboratory parameters in order to assess safety of lomitapide in Japanese and Caucasian subjects with elevated LDL-C. [ Time Frame: Samples will be taken pre-dose on Day 1 up to Day 27 post treatment. ] [ Designated as safety issue: Yes ]
    To assess the single dose and multiple dose safety of lomitapide in Japanese and Caucasian subjects with elevated LDL-C.

  • To evaluate the number of adverse events and changes in laboratory parameters in order to assess tolerability in Japanese and Caucasian subjects with elevated LDL-C. [ Time Frame: Samples will be taken pre-dose on Day 1 up to Day 27 post treatment ] [ Designated as safety issue: No ]
    To assess the single dose and multiple dose tolerability of lomitapide in Japanese and Caucasian subjects with elevated LDL-C.

  • To evaluate the number of adverse events and changes in laboratory parameters in order to assess pharmacodynamics(PD)of lomitapide in Japanese and Caucasian subjects with elevated LDL-C. [ Time Frame: Samples will be taken pre-dose on Day 1 up to Day 27 post treatment. ] [ Designated as safety issue: No ]
    To assess the pharmacodynamic(PD) of lomitapide in Japanese and Caucasian subjects with elevated LDL-C.


Enrollment: 72
Study Start Date: November 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
12 Japanese and 12 Caucasian subjects. 10 out of 12 will receive lomitapide and 2 will receive placebo.
Drug: lomitapide
Experimental: Cohort 2
8 Japanese and 8 Caucasian subjects. 6 out of 8 subjects will receive lomitapide and 2 will receive placebo.
Drug: lomitapide
Experimental: Cohort 3
8 Japanese and 8 Caucasian subjects. 6 out of 8 subjects will receive lomitapide and 2 will receive placebo.
Drug: lomitapide
Experimental: Cohort 4
8 Japanese and 8 Caucasian subjects. 6 out of 8 subjects will receive lomitapide and 2 will receive placebo.
Drug: lomitapide

  Eligibility

Ages Eligible for Study:   20 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 1. Subject is a healthy male 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 120mg/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).
  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.

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  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01760187

Locations
United Kingdom
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
  More Information

No publications provided

Responsible Party: Aegerion Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01760187     History of Changes
Other Study ID Numbers: AEGR-733-023, 2012-004220-37
Study First Received: November 21, 2012
Last Updated: January 21, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

ClinicalTrials.gov processed this record on October 19, 2014