Evaluate the Effect of Atorvastatin on the Pharmacokinetics of Lomitapide in Healthy 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 atorvastatin, a weak cytochrome P450 (CYP) 3A4 inhibitor, on the pharmacokinetics (PK) of lomitapide and its 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 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.

Official Title
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A Phase 1, Open-Label, Randomized, 2-Arm Study to Evaluate the Effect of Atorvastatin, a Weak CYP3A4 Inhibitor, on the Pharmacokinetics of Lomitapide in Healthy Subjects

Conditions
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Effect of Atorvastatin on the Pharmacokinetics of Lomitapide

Intervention / Treatment
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* Drug: lomitapide
* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females, between 18 and 55 years of age inclusive BMI between 18.5 and 32.0 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 medical exam 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 males will either be sterile or agree to use approved methods of contraception 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. 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 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 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: 55 Years

Sexes Eligible for Study
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All

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: Lomitapide & Atorvastatin - Taken Together<br>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) | Drug: lomitapide<br>* 20 mg dose<br>* Other names: Juxtapid;Drug: Atorvastatin<br>* 80 mg<br>* Other names: Lipitor;|
| Experimental: Lomitapide & Atorvastatin - Approx. 12 hours between<br>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) | Drug: lomitapide<br>* 20 mg dose<br>* Other names: Juxtapid;Drug: Atorvastatin<br>* 80 mg<br>* Other names: Lipitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing | 
| Tmax | Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing | 
| AUC0-t | Area under the concentration-time curve from zero to the last quantifiable concentration of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing | 
| AUC0-∞ | Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing | 
| t1/2 | Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing | 
| Tmax | Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing | 
| AUC0-t | Area under the concentration-time curve from zero to the last quantifiable concentration of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing | 
| AUC0-∞ | Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing | 
| t1/2 | Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |