Evaluate the Effect of Ethinyl Estradiol/Norgestimate on the Pharmacokinetics of Lomitapide in Healthy Female Subjects
Condition: Healthy
Intervention: lomitapide; EE/norgestimate
Intervention description: 20 mg; 1x0.035-mg EE/0.25-mg norgestimate tablet
Intervention MeSH terms: Norgestimate
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Effect; Ethinyl Estradiol/Norgestimate; Pharmacokinetics; Lomitapide.

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.
    

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.