Evaluate the Effect of Atorvastatin on the Pharmacokinetics of Lomitapide in Healthy Subjects.

NCT02080455 | Completed Phase 1 Results

• 1 other identifier: AEGR-733-024
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess the effect of atorvastatin, a weak cytochrome P450 (CYP) 3A4 inhibitor, on the pharmacokinetics (PK) of lomitapide and its 2 primary metabolites, M1 and M3.

Conditions

Effect of Atorvastatin on the Pharmacokinetics of Lomitapide

Outcome Measures

Primary Outcomes (5)

• Cmax

  Maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 \& M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1)

  Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing

• Tmax

  Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 \& M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1)

  Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing

• AUC0-t

  Area under the concentration-time curve from zero to the last quantifiable concentration of lomitapide and its 2 primary metabolites (M1 \& M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1)

  Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing

• AUC0-∞

  Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites (M1 \& M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1)

  Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing

• t1/2

  Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites (M1 \& M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1)

  Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing

Secondary Outcomes (5)

• Cmax

  Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing

• Tmax

  Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing

• AUC0-t

  Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing

• AUC0-∞

  Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing

• t1/2

  Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing

Study Arms (2)

Lomitapide & Atorvastatin - Taken Together

EXPERIMENTAL

2 single oral doses of lomitapide (20 mg) with a 14-day washout between (Day 1 \& Day 15) 11 single oral doses of atorvastatin (80 mg) (Day 11 through day 21)

Drug: lomitapide; Drug: Atorvastatin

Lomitapide & Atorvastatin - Approx. 12 hours between

EXPERIMENTAL

2 single oral doses of lomitapide (20 mg) with a 14-day washout between (Day 1 \& Day 15) 11 single oral doses of atorvastatin (80 mg) (Day 12 through day 22)

Drug: lomitapide; Drug: Atorvastatin

Interventions

lomitapide DRUG

20 mg dose

Also known as: Juxtapid

Lomitapide & Atorvastatin - Approx. 12 hours between; Lomitapide & Atorvastatin - Taken Together

Atorvastatin DRUG

80 mg

Also known as: Lipitor

Lomitapide & Atorvastatin - Approx. 12 hours between; Lomitapide & Atorvastatin - Taken Together

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males and females, between 18 and 55 years of age inclusive
• BMI between 18.5 and 32.0 kg/m2, inclusive; total body weight of \>110 lbs (50 kg);
• in good health, determined by no clinically significant or relevant abnormalities identified by a detailed medical history and medical exam
• creatine phosphokinase, AST, and ALT levels must be below 1.5 times the upper limit of normal
• clinical laboratory evaluations within the reference range for the test laboratory
• negative test for selected drugs of abuse
• negative hepatitis panel and negative HIV antibody screens
• males will either be sterile or agree to use approved methods of contraception
• all females must have a negative serum beta human chorionic gonadotropin pregnancy test and will be required to use a medically acceptable method of contraception.
• able to comprehend and willing to sign an Informed Consent Form

You may not qualify if:

• significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI, neurological, or psychiatric disorder
• history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
• history of stomach or intestinal surgery or resection
• history of Gilbert's Syndrome or suspicion of Gilbert's Syndrome
• subjects who have an abnormality in the 12-lead ECG
• use of any drugs of abuse for 6 months prior to Check-in;
• subjects who consume more than 14 units of alcohol per week or who have a significant history of alcoholism or drug/chemical abuse within 1 year prior to Check-in
• use of any tobacco- or nicotine-containing products within 6 months prior to Check-in;
• participation in any other investigational study drug trial within 30 days prior to Check-in;
• use of any prescription medications/products within 14 days prior to Check-in unless deemed acceptable by the Investigator and Sponsor
• use of any over-the-counter, nonprescription preparations within 7 days prior to Check-in, unless deemed acceptable by the Investigator and Sponsor
• use of alcohol-, grapefruit- (including star fruit), or caffeine-containing foods or beverages within 72 hours prior to Check-in and through Study Completion
• poor peripheral venous access;
• donation of blood (500 mL) from 30 days prior to Screening through Study Completion
• receipt of blood products within 2 months prior to Check-in;

Sponsors & Collaborators

• Aegerion Pharmaceuticals, Inc.: lead

Study Sites (1)

Covance Clinical Research Unit, Inc

Dallas, Texas, 75247, United States

Location

MeSH Terms

Interventions

BMS201038; Atorvastatin

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

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

alison.long@aegerion.com

617-242-5142

Study Officials

• Mark Sumeray, MD

  Cheif Medical Officer

  STUDY CHAIR

• T. Alex King, MD, CPI

  Covance

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: March 5, 2014
• First Posted: March 6, 2014
• Study Start: January 27, 2014
• Primary Completion: March 7, 2014
• Study Completion: March 7, 2014
• Last Updated: March 10, 2020
• Results First Posted: March 10, 2020

Record last verified: 2020-02

Locations

US (1)