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

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ClinicalTrials.gov Identifier: NCT01760187
Recruitment Status : Completed
First Posted : January 4, 2013
Results First Posted : November 20, 2018
Last Update Posted : November 20, 2018
Sponsor:
Collaborator:
Richmond Pharmacology Limited
Information provided by (Responsible Party):
Aegerion Pharmaceuticals, Inc.

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

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Study Type : Interventional  (Clinical Trial)
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 : November 7, 2012
Actual Primary Completion Date : June 3, 2013
Actual Study Completion Date : June 3, 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Lomitapide

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



Primary Outcome Measures :
  1. Cmax for Lomitapide [ Time Frame: 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

  2. Tmax for Lomitapide [ Time Frame: 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

  3. AUC0-t for Lomitapide [ Time Frame: 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

  4. AUC0-∞ for Lomitapide [ Time Frame: 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

  5. t1/2 for Lomitapide [ Time Frame: 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

  6. Cmax for Lomitapide [ Time Frame: 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

  7. Tmax for Lomitapide [ Time Frame: 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

  8. AUC0-t for Lomitapide [ Time Frame: 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

  9. t1/2 for Lomitapide [ Time Frame: 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 :
  1. Cmax for M1 [ Time Frame: 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

  2. Tmax for M1 [ Time Frame: 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

  3. AUC0-t for M1 [ Time Frame: 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

  4. AUC0-∞ for M1 [ Time Frame: 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

  5. t1/2 for M1 [ Time Frame: 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

  6. Cmax for M3 [ Time Frame: 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

  7. Tmax for M3 [ Time Frame: 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

  8. AUC0-t for M3 [ Time Frame: 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

  9. AUC0-∞ for M3 [ Time Frame: 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

  10. t1/2 for M3 [ Time Frame: 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

  11. Cmax for M1 [ Time Frame: 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

  12. Tmax for M1 [ Time Frame: 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

  13. AUC0-t for M1 [ Time Frame: 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

  14. t1/2 for M1 [ Time Frame: 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

  15. Cmax for M3 [ Time Frame: 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

  16. Tmax for M3 [ Time Frame: 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

  17. AUC0-t for M3 [ Time Frame: 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

  18. t1/2 for M3 [ Time Frame: 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



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Ages Eligible for Study:   20 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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:

  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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01760187


Locations
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United Kingdom
Richmond Pharmacology Ltd
Croydon, Surrey, United Kingdom, CR7 7YE
Sponsors and Collaborators
Aegerion Pharmaceuticals, Inc.
Richmond Pharmacology Limited
Investigators
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Principal Investigator: Ulrike Lorch, MD FRCA FFPM Richmond Pharmacology Limited

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Responsible Party: Aegerion Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01760187     History of Changes
Other Study ID Numbers: AEGR-733-023
2012-004220-37 ( EudraCT Number )
First Posted: January 4, 2013    Key Record Dates
Results First Posted: November 20, 2018
Last Update Posted: November 20, 2018
Last Verified: November 2018