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

Aegerion Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Effect of Atorvastatin on the Pharmacokinetics of Lomitapide

Treatments: Drug: Atorvastatin; Drug: lomitapide

Study type: Interventional

Funder types: Industry

Identifiers

NCT02080455

AEGR-733-024

Details and patient eligibility

About

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.

Full description

This study will be a single center, randomized, open-label, 2-arm study to evaluate the effects of atorvastatin, a weak CYP3A4 inhibitor, on the PK of lomitapide in healthy male and female subjects when atorvastatin is administered simultaneously with lomitapide and when it is administered 12 hours after lomitapide.

Enrollment: 32 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy males and females, between 18 and 55 years of age inclusive
2. BMI between 18.5 and 32.0 kg/m2, inclusive; total body weight of >110 lbs (50 kg);
3. in good health, determined by no clinically significant or relevant abnormalities identified by a detailed medical history and medical exam
4. creatine phosphokinase, AST, and ALT levels must be below 1.5 times the upper limit of normal
5. clinical laboratory evaluations within the reference range for the test laboratory
6. negative test for selected drugs of abuse
7. negative hepatitis panel and negative HIV antibody screens
8. males will either be sterile or agree to use approved methods of contraception
9. 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.
10. able to comprehend and willing to sign an Informed Consent Form

Exclusion criteria

1. significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI, neurological, or psychiatric disorder
2. history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
3. history of stomach or intestinal surgery or resection
4. history of Gilbert's Syndrome or suspicion of Gilbert's Syndrome
5. subjects who have an abnormality in the 12-lead ECG
6. use of any drugs of abuse for 6 months prior to Check-in;
7. 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
8. use of any tobacco- or nicotine-containing products within 6 months prior to Check-in;
9. participation in any other investigational study drug trial within 30 days prior to Check-in;
10. use of any prescription medications/products within 14 days prior to Check-in unless deemed acceptable by the Investigator and Sponsor
11. use of any over-the-counter, nonprescription preparations within 7 days prior to Check-in, unless deemed acceptable by the Investigator and Sponsor
12. use of alcohol-, grapefruit- (including star fruit), or caffeine-containing foods or beverages within 72 hours prior to Check-in and through Study Completion
13. poor peripheral venous access;
14. donation of blood (500 mL) from 30 days prior to Screening through Study Completion
15. receipt of blood products within 2 months prior to Check-in;
16. any acute or chronic condition, scheduled hospitalization (inclusive of elective surgery during study) or scheduled travel prior to completion of all study procedures which, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in this clinical study;
17. subjects who, in the opinion of the Investigator, should not participate in this study.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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32 participants in 2 patient groups

Lomitapide & Atorvastatin - Taken Together

Experimental group

Description:

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)

Treatment:

Drug: Atorvastatin

Drug: lomitapide

Lomitapide & Atorvastatin - Approx. 12 hours between

Experimental group

Description:

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)

Treatment:

Drug: Atorvastatin

Drug: lomitapide