Evaluate the Effect of Ethinyl Estradiol/Norgestimate on the Pharmacokinetics of Lomitapide in Healthy Female Subjects

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: lomitapide
Drug: EE/norgestimate

Registration Number: NCT02080468

Lead Sponsor: Aegerion Pharmaceuticals, Inc.

Brief Summary: The primary objective of this study is to assess the effect of ethinyl estradiol (EE)/norgestimate, a weak cytochrome P450 (CYP) 3A4 inhibitor, on the pharmacokinetics (PK) of lomitapide and 2 primary metabolites, M1 and M3.

Detailed Description: This study will be a single center, randomized, open-label, 2 arm study to evaluate the effects of EE/norgestimate, a weak CYP3A4 inhibitor, on the PK of lomitapide in healthy female subjects when EE/norgestimate is administered simultaneously with lomitapide and when administration is separated by 12 hours.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 32

Inclusion Criteria

Healthy females, between 18 and 40 years of age inclusive
BMI between 18.5 and 30.0 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 physical exam
no known history of hypersensitivity or previous intolerance to lomitapide or EE/norgestimate
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
are of childbearing potential(ie, not postmenopausal or surgically sterile). All subjects must have a negative serum beta pregnancy test.
able to comprehend and willing to sign an Informed Consent Form

Exclusion Criteria

significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI, neurological, or psychiatric disorder
history of unexplained breast abnormalities or abnormal uterine bleeding
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
use of oral (except scheduled administration of EE/norgestimate), implantable, injectable, or transdermal contraceptives
use of hormone replacement therapy
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;
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;
subjects who, in the opinion of the Investigator, should not participate in this study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Lomitapide & EE/Norgestimate - Taken Together	EE/norgestimate	Lomitapide \& EE/Norgestimate - Taken Together 2 single oral doses of lomitapide (20 mg) (Day 1 \& Day 22) 21 single oral doses of EE/Norgestimate(Day 8 through day 28)
Arm 2: Lomitapide & EE/Norgestimate - Taken 12 Hours Apart	EE/norgestimate	Lomitapide \& EE/Norgestimate - Taken 12 hours apart 2 single oral doses of lomitapide (20 mg) (Day 1 \& Day 22) 21 single oral doses of EE/Norgestimate(Day 9 through day 29)
Arm 1: Lomitapide & EE/Norgestimate - Taken Together	lomitapide	Lomitapide \& EE/Norgestimate - Taken Together 2 single oral doses of lomitapide (20 mg) (Day 1 \& Day 22) 21 single oral doses of EE/Norgestimate(Day 8 through day 28)
Arm 2: Lomitapide & EE/Norgestimate - Taken 12 Hours Apart	lomitapide	Lomitapide \& EE/Norgestimate - Taken 12 hours apart 2 single oral doses of lomitapide (20 mg) (Day 1 \& Day 22) 21 single oral doses of EE/Norgestimate(Day 9 through day 29)

Primary Outcome Measures

Name	Time	Method
Tmax for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)	1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing	Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites, M1 \& M3.
AUC0-∞ for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)	1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing	Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites, M1 \& M3.
t1/2 for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)	1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing	Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites, M1 \& M3.
Cmax for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)	1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing	Maximum observed plasma concentration of lomitapide and its 2 primary metabolites, M1 \& M3
AUC0-t for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)	1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing	Area under the concentration-time curve from zero to last quantifiable concentration of lomitapide and its 2 primary metabolites, M1 \& M3.

Secondary Outcome Measures

Name	Time	Method
Tmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)	1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing	Time to reach maximum observed plasma concentration of lomitapide and its metabolites, M1 \& M3.
t1/2 for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)	1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing	Apparent terminal elimination half-life of lomitapide and its metabolites, M1 \& M3.
Cmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)	1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing	Maximum observed plasma concentration of lomitapide and its metabolites, M1 \& M3.
AUC0-t for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)	1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing	Area under the concentration-time curve from zero to last quantifiable concentration of lomitapide and its metabolites, M1 \& M3.
AUC0-∞ for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)	1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing	Area under the concentration-time curve from zero to infinity of lomitapide and its metabolites, M1 \& M3.