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

NCT01915771 | Completed Phase 1 Results

• 2 other identifiers: AEGR-733-0262013-002692-17
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Intra-subject Variability of Pharmacokinetics

Outcome Measures

Primary Outcomes (6)

• Cmax

  Maximum observed concentration of lomitapide and its metabolites, M1 \& M3.

  Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.

• Tmax

  Time to reach maximum plasma concentration

  Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.

• AUC0-t

  Area under the concentration-time curve from hour 0 to the last measurable concentration of lomitapide and its metabolites, M1 \& M3.

  Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.

• AUC0-∞

  Area under the concentration-time curve extrapolated to infinity for lomitapide and its metabolites, M1 \& M3.

  Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.

• λz

  Elimination rate constant estimated from individual linear regression of the terminal part of the log concentration vs time curve

  Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.

• t1/2

  Apparent terminal elimination half-life

  Pre dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours post dose.

Study Arms (1)

lomitapide

EXPERIMENTAL

It will comprise of 2 single oral doses with at least a 14-day washout between doses.

Drug: lomitapide

Interventions

lomitapide DRUG

20 mg dose

Also known as: Juxtapid

lomitapide

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is a non-smoking healthy male or female, aged between 18 and 40 years of age.
• Subject has a BMI of 18.5 - 25 kg/m2.
• Subject has total body weight between \> 50 kg to ≤ 100 kg.
• Subjects must agree to use acceptable methods of contraception.
• All females, regardless of childbearing potential, must have a negative serum beta human chorionic gonadotropin pregnancy test at Screening and on admission.
• In good health, determined by no clinically significant or relevant abnormalities identified by a detailed medical history \& full physical examination.
• No known history of hypersensitivity or previous intolerance to lomitapide.
• 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.

You may not qualify if:

• Subject has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion.
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs.
• Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator;
• 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.
• History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrinological, allergic, dermatological, metabolic, neurological, psychiatric or other disease.
• History or laboratory evidence of Gilbert's syndrome.
• 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).
• Use of any drugs of abuse within 6 months prior to admission.
• 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).
• History or clinical evidence of alcohol or drug abuse within one year prior to admission.
• Mentally handicapped.
• Participation in a drug trial within 90 days prior to first drug administration.
• Use of any prescription medication within 2 weeks prior to admission (Day -1), with the exception of the oral contraceptive pill.
• Use of any substance inducing or inhibiting CYP3A4 enzymes within 30 days prior to admission (Day -1).

Sponsors & Collaborators

• Aegerion Pharmaceuticals, Inc.: lead

Study Sites (1)

Richmond Pharmacology

Croydon, Surrey, CR7 7YE, United Kingdom

Location

MeSH Terms

Interventions

BMS201038

Results Point of Contact

• Title: Alison Long, MD - VP Clinical
• Organization: Aegerion Pharmaceuticals, Inc.

alison.long@aegerion.com

617-500-5142

Study Officials

• Mark Sumeray, MD

  Aegerion Pharmaceuticals, Inc.

  STUDY CHAIR

• Ulrike Lorch, MD

  Richmond Pharmacology Limited

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2013
• First Posted: August 5, 2013
• Study Start: July 29, 2013
• Primary Completion: August 23, 2013
• Study Completion: August 23, 2013
• Last Updated: March 11, 2020
• Results First Posted: March 11, 2020

Record last verified: 2020-02

Locations

GB (1)