Pharmacokinetic Drug Interactions of AEGR-733 on Lipid-lowering Agents
Condition: Healthy
Intervention: atorvastatin; simvastatin; ezetimibe; fenofibrate; dextromethorphan; Extended Release Niacin
Intervention description: Atrovastatin 20 mg and AEGR-733 10 mg or 60 mg; Simvastatin 20 mg and AEGR-733 10 mg or 60 mg; Ezetimibe 10 mg and AEGR-733 10 mg; Micronized Fenofibrate 145 mg and AEGR-733 10 mg; Dextromethorphan 30 mg and AEGR-733 10 mg; 1000 mg ER niacin and AEGR-733 10 mg
Intervention MeSH terms: Niacin; Dextromethorphan; Atorvastatin; Simvastatin; Ezetimibe; Fenofibrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 125.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: healthy volunteers

Summary:

      This phase II, open-label research study was conducted in 129 healthy volunteers. Each
      subject will be given one initial oral dose of one of 7 FDA-approved medications (probe
      drugs), followed by a 7 day period where subjects receive the study medication AEGR-733 at 10
      or 60 mg. On study day 8 subjects will receive the second oral dose of the same probe drug
      that was given on day 1 and a last dose of AEGR-733 (total of 7 doses).Subjects will return
      in 1 week for a final safety visit. Each FDA- approved probe drug will be given to ten (10)
      or fifteen (15) subjects.

      Safety, pharmacokinetic and pharmacodynamic assessments will be performed.
    

Eligibility criteria:

        Inclusion Criteria:

        Males and non-pregnant/non-lactating female subjects between the ages of 18 and 70 who are
        in good overall health.

        To be eligible for enrollment in this study, patients must meet all of the following
        criteria:

          1. Men and women between the ages of 18 and 70

          2. Women of child-bearing potential, that is, women not surgically sterilized and between
             menarche and 1 year post menopause, must test negative for pregnancy at the time of
             enrollment based on a urine pregnancy test and agree to use a reliable method of
             non-medication birth control (for example, a reliable barrier method of birth control
             [diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms
             with contraceptive foam; intrauterine devices]; partner with vasectomy; or abstinence)
             during the study and for one month following the last dose of study drug.

          3. Subjects must be in good overall health

          4. Subjects must be able to comprehend and willing to provide a signed IRB approved
             Informed Consent Form.

          5. Subjects must be willing to comply with all study-related procedures.

        Exclusion Criteria:

          1. Known atherosclerotic cardiovascular disease, including coronary disease,
             cerebrovascular disease, or peripheral vascular disease

          2. History of diabetes mellitus or fasting glucose > 126 mg/dL at the screening visit.

          3. History of a non-skin malignancy within the previous 5 years

          4. Renal insufficiency as defined by creatinine > 1.3 mg/dl

          5. Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory
             condition

          6. History of hypertension

          7. Known coagulopathy and /or elevated PT/PTT >1.5 x ULN

          8. Oral history of HIV positive

          9. Patients who have undergone any organ transplant

         10. Known active fibrotic or cirrhotic disease; ALT or AST > 1.5x ULN

         11. Any major surgery within the previous 3 months

         12. Individuals who currently use tobacco products or have done so in the previous 30 days

         13. History of drug abuse (< 3 years)

         14. Regular use of alcoholic beverages (> 7 drinks/day)

         15. Subjects who do not agree to abstain from consuming alcoholic beverages during the
             entire study duration.

         16. Body mass index (BMI) > 30 kg/m2 or < 18.5 kg/m2

         17. Participation in an investigational drug study within 6 weeks prior to the screening
             visit

         18. Serious or unstable medical or psychological conditions that, in the opinion of the
             investigator, would compromise the subject's safety or successful participation in the
             study will be excluded.

         19. Currently taking any prescription, including oral contraceptives, or OTC medication
             regularly that cannot be stopped for at least 30 days prior to enrollment until
             completion of the study

         20. Regular consumers of grapefruit juice, or have taken any medications known to be
             metabolized by CYP 3A4 within 4 weeks prior to the screening visit (ie. SSRIs,
             anti-fungals, anti-biotics, etc)

         21. History of myalgia with a statin or unknown hypersensitivity to any statin, zetia,
             AEGR-733, or fenofibrate.