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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.

Tracking Information
First Submitted Date  ICMJE November 21, 2012
First Posted Date  ICMJE January 4, 2013
Results First Submitted Date  ICMJE June 23, 2015
Results First Posted Date  ICMJE November 20, 2018
Last Update Posted Date November 20, 2018
Actual Study Start Date  ICMJE November 7, 2012
Actual Primary Completion Date June 3, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 16, 2018)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: January 3, 2013)
Pharmacokinetics (PK) comparison [ Time Frame: Pharmacokinetic samples will be taken pre-dose on Day 1 up to Day 27 post treatment. ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 16, 2018)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2013)
  • 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. ]
    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 ]
    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. ]
    To assess the pharmacodynamic(PD) of lomitapide in Japanese and Caucasian subjects with elevated LDL-C.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I Study of the Safety, Tolerability, PK & PD of Lomitapide in Japanese and Caucasian Subjects With Elevated LDL-C
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Healthy Volunteer
Intervention  ICMJE Drug: lomitapide
Study Arms  ICMJE
  • Experimental: Cohort 1
    12 Japanese and 12 Caucasian subjects. 10 out of 12 will receive 10 mg lomitapide and 2 will receive placebo.
    Intervention: 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.
    Intervention: 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.
    Intervention: 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.
    Intervention: Drug: lomitapide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 3, 2013)
72
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 3, 2013
Actual Primary Completion Date June 3, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01760187
Other Study ID Numbers  ICMJE AEGR-733-023
2012-004220-37 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Aegerion Pharmaceuticals, Inc.
Study Sponsor  ICMJE Aegerion Pharmaceuticals, Inc.
Collaborators  ICMJE Richmond Pharmacology Limited
Investigators  ICMJE
Principal Investigator: Ulrike Lorch, MD FRCA FFPM Richmond Pharmacology Limited
PRS Account Aegerion Pharmaceuticals, Inc.
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP