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

A Phase 1, Open-Label, Randomized, 2-Arm Study to Evaluate the Effect of Ethinyl Estradiol/Norgestimate (Ortho Cyclen®), a Weak CYP3A4 Inhibitor, on the Pharmacokinetics of Lomitapide in Healthy Female Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: lomitapide; Drug: EE/norgestimate

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Clinical Research Unit, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Healthy females, between 18 and 40 years of age inclusive
2. BMI between 18.5 and 30.0 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 physical exam
4. no known history of hypersensitivity or previous intolerance to lomitapide or EE/norgestimate
5. creatine phosphokinase, AST, and ALT levels must be below 1.5 times the upper limit of normal
6. clinical laboratory evaluations within the reference range for the test laboratory
7. negative test for selected drugs of abuse
8. negative hepatitis panel and negative HIV antibody screens
9. are of childbearing potential(ie, not postmenopausal or surgically sterile). All subjects must have a negative serum beta pregnancy test.
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 unexplained breast abnormalities or abnormal uterine bleeding
3. history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
4. history of stomach or intestinal surgery or resection
5. history of Gilbert's Syndrome or suspicion of Gilbert's Syndrome
6. subjects who have an abnormality in the 12-lead ECG
7. use of any drugs of abuse for 6 months prior to Check-in;
8. 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
9. use of any tobacco- or nicotine-containing products within 6 months prior to Check-in;
10. participation in any other investigational study drug trial within 30 days prior to Check-in;
11. use of any prescription medications/products within 14 days prior to Check-in unless deemed acceptable by the Investigator and Sponsor
12. use of any over-the-counter, nonprescription preparations within 7 days prior to Check-in, unless deemed acceptable by the Investigator and Sponsor
13. use of alcohol-, grapefruit- (including star fruit), or caffeine-containing foods or beverages within 72 hours prior to Check-in and through Study Completion
14. use of oral (except scheduled administration of EE/norgestimate), implantable, injectable, or transdermal contraceptives
15. use of hormone replacement therapy
16. poor peripheral venous access;
17. donation of blood (500 mL) from 30 days prior to Screening through Study Completion
18. receipt of blood products within 2 months prior to Check-in;
19. 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;
20. subjects who, in the opinion of the Investigator, should not participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Lomitapide & EE/Norgestimate - Taken Together; 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)	Drug: lomitapide; 20 mg; Other Names: Juxtapid; Drug: EE/norgestimate; 1x0.035-mg EE/0.25-mg norgestimate tablet; Other Names: Ortho Cylclen
Experimental: Arm 2: Lomitapide & EE/Norgestimate - Taken 12 Hours Apart; 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)	Drug: lomitapide; 20 mg; Other Names: Juxtapid; Drug: EE/norgestimate; 1x0.035-mg EE/0.25-mg norgestimate tablet; Other Names: Ortho Cylclen

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Aegerion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2014
• Primary Completion (Actual): April 24, 2014
• Study Completion (Actual): April 24, 2014

Study Registration Dates

• First Submitted: March 5, 2014
• First Submitted That Met QC Criteria: March 5, 2014
• First Posted (Estimate): March 6, 2014

Study Record Updates

• Last Update Posted (Actual): March 11, 2019
• Last Update Submitted That Met QC Criteria: November 16, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Effect; Ethinyl Estradiol/Norgestimate; Lomitapide.
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Norgestimate
• Other Study ID Numbers: AEGR-733-029