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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: lomitapide
* Drug: EE/norgestimate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Lomitapide & EE/Norgestimate - Taken Together<br>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<br>* 20 mg<br>* Other names: Juxtapid;Drug: EE/norgestimate<br>* 1x0.035-mg EE/0.25-mg norgestimate tablet<br>* Other names: Ortho Cylclen;|
| Experimental: Arm 2: Lomitapide & EE/Norgestimate - Taken 12 Hours Apart<br>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<br>* 20 mg<br>* Other names: Juxtapid;Drug: EE/norgestimate<br>* 1x0.035-mg EE/0.25-mg norgestimate tablet<br>* Other names: Ortho Cylclen;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Effect, Ethinyl Estradiol/Norgestimate, Pharmacokinetics, Lomitapide.