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Study to Determine the Intra-subject Variability of Pharmacokinetics of Lomitapide in Healthy Subjects

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ClinicalTrials.gov Identifier: NCT01915771
Recruitment Status : Completed
First Posted : August 5, 2013
Results First Posted : March 11, 2020
Last Update Posted : March 11, 2020
Sponsor:
Information provided by (Responsible Party):
Aegerion Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE August 1, 2013
First Posted Date  ICMJE August 5, 2013
Results First Submitted Date  ICMJE June 23, 2015
Results First Posted Date  ICMJE March 11, 2020
Last Update Posted Date March 11, 2020
Actual Study Start Date  ICMJE July 29, 2013
Actual Primary Completion Date August 23, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2020)
  • Cmax [ Time Frame: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose. ]
    Maximum observed concentration of lomitapide and its metabolites, M1 & M3.
  • Tmax [ Time Frame: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose. ]
    Time to reach maximum plasma concentration
  • AUC0-t [ Time Frame: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose. ]
    Area under the concentration-time curve from hour 0 to the last measurable concentration of lomitapide and its metabolites, M1 & M3.
  • AUC0-∞ [ Time Frame: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose. ]
    Area under the concentration-time curve extrapolated to infinity for lomitapide and its metabolites, M1 & M3.
  • λz [ Time Frame: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose. ]
    Elimination rate constant estimated from individual linear regression of the terminal part of the log concentration vs time curve
  • t1/2 [ Time Frame: Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose. ]
    Apparent terminal elimination half-life
Original Primary Outcome Measures  ICMJE
 (submitted: August 1, 2013)
  • Cmax [ Time Frame: Pre dose and at 1,2,3,4,5,6,8,10,12,18,24,48,72,96,120,144 and 168 hours post dose. ]
    maximum observed concentration
  • Tmax [ Time Frame: Pre dose and at 1,2,3,4,5,6,8,10,12,18,24,48,72,96,120,144 and 168 hours post dose. ]
    time to maximum observed concentration
  • t1/2 [ Time Frame: Pre dose and at 1,2,3,4,5,6,8,10,12,18,24,48,72,96,120,144 and 168 hours post dose. ]
    Apparent terminal elimination half-life
  • AUC0-t [ Time Frame: Pre dose and at 1,2,3,4,5,6,8,10,12,18,24,48,72,96,120,144 and 168 hours post dose. ]
    area under the concentration-time curve from 0 to the last measurable concentration
  • AUC0-x [ Time Frame: Pre dose and at 1,2,3,4,5,6,8,10,12,18,24,48,72,96,120,144 and 168 hours post dose. ]
    area under the concentration-time curve extrapolated to infinity
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Determine the Intra-subject Variability of Pharmacokinetics of Lomitapide in Healthy Subjects
Official Title  ICMJE A Phase 1, Open-label, Crossover Study to Determine the Intra-subject Variability of the Pharmacokinetics of Single Oral CapsuleDose of 20 mg Lomitapide in Healthy Subjects
Brief Summary

Objectives:

To evaluate the intra-subject variability of the pharmacokinetics (PK) of single oral capsule doses of 20 mg lomitapide.

Detailed Description This study will be a single centre, open-label study. It will comprise of 2 single oral doses with at least a 14-day washout between doses. Following the first dose subjects will be discharged from the unit for the remainder of the washout period. Subjects will be re-admitted to the unit on Day -1 (Period 2) and following an overnight fast they will be administered the second dose on Day 1 (Period 2). Subjects will be discharged from the unit following the 168 h PK blood draw.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Intra-subject Variability of Pharmacokinetics
Intervention  ICMJE Drug: lomitapide
20 mg dose
Other Name: Juxtapid
Study Arms  ICMJE Experimental: lomitapide
It will comprise of 2 single oral doses with at least a 14-day washout between doses.
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: August 1, 2013)
15
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 23, 2013
Actual Primary Completion Date August 23, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subject is a non-smoking healthy male or female, aged between 18 and 40 years of age.
  2. Subject has a BMI of 18.5 - 25 kg/m2.
  3. Subject has total body weight between > 50 kg to ≤ 100 kg.
  4. Subjects must agree to use acceptable methods of contraception.
  5. All females, regardless of childbearing potential, must have a negative serum beta human chorionic gonadotropin pregnancy test at Screening and on admission.
  6. In good health, determined by no clinically significant or relevant abnormalities identified by a detailed medical history & full physical examination.
  7. No known history of hypersensitivity or previous intolerance to lomitapide.
  8. 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. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs.
  3. Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations.
  4. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator;
  5. Electrocardiogram (ECG) abnormalities in the standard 12-lead ECG (at screening) such as a QTcF interval of >450 msec, a history of a prolonged QTc interval or Brugada syndrome.
  6. History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrinological, allergic, dermatological, metabolic, neurological, psychiatric or other disease.
  7. History or laboratory evidence of Gilbert's syndrome.
  8. 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).
  9. Use of any drugs of abuse within 6 months prior to admission.
  10. Confirmed positive results from urine drug screen (amphetamines, benzodiazepines, cocaine, cannabinoids, opiates, barbiturates and methadone) or from the alcohol breath test at screening and on admission (Day -1).
  11. History or clinical evidence of alcohol or drug abuse within one year prior to admission.
  12. Mentally handicapped.
  13. Participation in a drug trial within 90 days prior to first drug administration.
  14. Use of any prescription medication within 2 weeks prior to admission (Day -1), with the exception of the oral contraceptive pill.
  15. Use of any substance inducing or inhibiting CYP3A4 enzymes within 30 days prior to admission (Day -1).
  16. Use of any over-the-counter (OTC) medication (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days prior to admission (Day -1), unless deemed acceptable by the Investigator and Sponsor.
  17. Use of alcohol-, grapefruit-, starfruit-, or caffeine-containing foods or beverages within 72 hours prior to admission and through Study Completion.
  18. Donation of more than 500 mL of blood within 90 days prior to drug administration.
  19. Receipt of blood products within 2 months prior to admission.
  20. Poor peripheral venous access.
  21. Use of any tobacco- or nicotine-containing products within 6 months prior to admission (Day -1).
  22. Any acute or chronic condition, scheduled hospitalisation (inclusive of elective surgery during study), or scheduled travel prior to completion of all study procedures.
  23. Any circumstances or conditions, which, in the opinion of the PI, may affect full participation in the trial or compliance with the protocol.
  24. Legal incapacity or limited legal capacity at screening.
  25. Subjects who are vegetarians, vegans or have any dietary restrictions conflicting with the study standardised menus.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 40 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 NCT01915771
Other Study ID Numbers  ICMJE AEGR-733-026
2013-002692-17 ( 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 Not Provided
Investigators  ICMJE
Study Chair: Mark Sumeray, MD Aegerion Pharmaceuticals, Inc.
Principal Investigator: Ulrike Lorch, MD Richmond Pharmacology Limited
PRS Account Aegerion Pharmaceuticals, Inc.
Verification Date February 2020

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