A Comparative Bioavailability Study of Lomitapide 20 mg Intact vs Sprinkled

• ClinicalTrials.gov Identifier: NCT02044419
• Recruitment Status: Completed
• First Posted: January 24, 2014
• Results First Posted: February 13, 2018
• Last Update Posted: February 13, 2018
• Sponsor: Aegerion Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Aegerion Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: November 6, 2013
• First Posted Date: January 24, 2014
• Results First Submitted Date: June 23, 2015
• Results First Posted Date: February 13, 2018
• Last Update Posted Date: February 13, 2018
• Actual Study Start Date: October 30, 2013
• Actual Primary Completion Date: December 23, 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 8, 2018)

• AUC0-t [ Time Frame: predose 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).
• Cmax [ Time Frame: predose 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: predose 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 of lomitapide and its metabolites (M1& M3).
• t1/2 [ Time Frame: predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post-dose ]
  Terminal elimination half-life of lomitapide and its metabolites (M1& M3).
• AUC0-∞ [ Time Frame: predose 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 plasma concentration vs time curve from zero to infinity of lomitapide and its metabolites (M1& M3).
• λz [ Time Frame: predose 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 of lomitapide and its metabolites (M1& M3).

Original Primary Outcome Measures (submitted: January 22, 2014)

AUC 0-t [ Time Frame: pre dose through 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).

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: January 22, 2014)

• Cmax [ Time Frame: pre dose through 168 hours post dose ]
  Maximum observed concentration of lomitapide and its metabolites (M1 & M3)
• Tmax [ Time Frame: pre dose through 168 hours post dose ]
  Timed to maximum observed concentration of lomitapide and its metabolites (M1 & M3)
• t1/2 [ Time Frame: pre dose through 168 post dose ]
  Apparent terminal elimination half-life of lomitapide and its metabolites (M1 & M3)
• λz [ Time Frame: pre dose through 168 hours post dose ]
  Elimination rate constant of lomitapide and its metabolites (M1 & M3)
• AUC inf [ Time Frame: Pre dose through 168 hours post dose ]
  Area under the concentration-time curve extrapolated to infinity of lomitapide and its metabolites (M1 & M3)

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: January 22, 2014)

To evaluate the number of adverse events and changes in laboratory parameters in order to assess safety of lomitapide. [ Time Frame: pre dose through 168 hours post dose ]

Standard laboratory safety tests (hemotology, biochemistry and urinalysis), vital signs (temperature, blood pressure and heart rate), physical examination, 12-lead ECG, and AE monitoring.

Descriptive Information

• Brief Title: A Comparative Bioavailability Study of Lomitapide 20 mg Intact vs Sprinkled
• Official Title: A Phase 1, Open-label, Randomised, Crossover Study to Determine the Comparative Bioavailability of 20 mg Lomitapide Where the Contents Have Been Opened and Sprinkled in Applesauce or Mashed Banana ("Sprinkled Contents") to a Single Oral Capsule Dose of 20 mg Lomitapide ("Intact Capsule") in Healthy Subjects
• Brief Summary: To compare the relative bioavailability of lomitapide when administered by sprinkling the contents of a 20 mg capsule of lomitapide in applesauce or in mashed banana to a single oral intact capsule dose of 20 mg lomitapide in healthy subjects.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Healthy

Intervention

Drug: lomitapide

Other Names:

• Juxtapid
• Lojuxta

Study Arms

• Experimental: lomitapide sprinkled in applesauce
  Contents of single 20 mg capsule of lomitapide sprinkled in applesauce
  Intervention: Drug: lomitapide
• Experimental: lomitapide sprinkled in mashed banana
  Contents of single 20 mg capsule of lomitapide sprinkled in mashed banana
  Intervention: Drug: lomitapide
• Experimental: lomitapide (intact)
  Intact capsule of 20 mg lomitapide
  Intervention: Drug: lomitapide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 22, 2014): 32
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: December 23, 2013
• Actual Primary Completion Date: December 23, 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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, applesauce, and/or banana.
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

• Sexes Eligible for Study: All

• Ages: 18 Years to 40 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT02044419
• Other Study ID Numbers: AEGR-733-032
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Aegerion Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Aegerion Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Mark Sumeray, MD; Aegerion Pharmaceuticals, Inc.
• Principal Investigator: Ulrike Lorch, MD; Richmond Phamacology, LTD

• PRS Account: Aegerion Pharmaceuticals, Inc.
• Verification Date: February 2018