Clinical trial NCT02080468: Evaluate the Effect of Ethinyl Estradiol/Norgestimate on the Pharmacokinetics of Lomitapide in Healthy Female Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Effect
Ethinyl Estradiol/Norgestimate
Pharmacokinetics
Lomitapide.
Lead sponsor: Aegerion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-03-06
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cmax for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing
measure: Tmax for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing
measure: AUC0-t for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing
measure: AUC0-∞ for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing
measure: t1/2 for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing
Secondary outcomes:
measure: Cmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing
measure: Tmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing
measure: AUC0-t for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing
measure: AUC0-∞ for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing
measure: t1/2 for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Covance Clinical Research Unit, Inc
state: Texas
Study officials:
affiliation: Cheif Medical Officer
name: Mark Sumeray, MD
role: STUDY_CHAIR
affiliation: Covance
name: T. Alex King, MD, CPI
role: PRINCIPAL_INVESTIGATOR
References: