The Effect of Various Amounts of Fat on PK of Oral Testosterone Undecanoate
Condition: Hypogonadism
MeSH terms: Hypogonadism
Intervention: Oral Testosterone Undecanoate
Intervention description: All study participants received Oral TU dose of 237 mg TU twice daily before breakfast and dinner for 14 days and throughout 5 crossover periods
Intervention MeSH terms: Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Intervention model description: Open-label, randomized, 5-period crossover food effect study
Masking: None (Open Label)
Enrollment: 18.0
Sex: Male
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      A Phase 2, open-label, randomized, cross-over, pharmacokinetic study designed to determine
      the effect of meals of various amounts of fat given immediately prior to dosing on the
      pharmacokinetics of oral testosterone undecanoate. Approximately 20 hypogonadal subjects will
      be dosed for a 14 day run-in period. This will be followed by a randomized sequence of five
      periods over a 6 day confinement period. Subjects will receive a randomly ordered sequence of
      breakfast meals containing various amounts of fat, fasting, 15 g, 30 g, 45 g and a high fat
      breakfast consistent Guidance for Industry on Food-Effect Bioavailability and Fed
      Bioequivalence Studies.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Man 18 to 65 years of age, inclusive, with a clinical diagnosis of hypogonadism
             (signs/symptoms consistent with hypogonadism for testosterone naïve subjects and
             history of signs/symptoms for subjects who have received prior treatment) as well as
             testosterone levels consistent with hypogonadism as defined by 2 morning total T
             values of <300 ng/dL (between 6:00 and 10:00 AM drawn on 2 separate days
             [approximately 7 (±2) days apart].

          2. Adequate venous access in the left or right arm to allow collection of a number of
             blood samples via a venous cannula.

          3. Must be naïve to androgen-replacement therapy or washed out of prior androgen
             replacement therapies; that is, be willing to cease current T treatment or currently
             not be taking T treatment, (washout durations specified in exclusion criterion #1).
             Subjects must remain off all forms of T, except for dispensed study drug, throughout
             the entire study.

          4. Subjects on replacement therapy for hypopituitarism or multiple endocrine deficiencies
             must be on stable doses of thyroid hormone and adrenal replacement hormones for at
             least 14 days before Screen 1.

          5. Has voluntarily given written informed consent to participate in this study.

        Exclusion Criteria:

          1. Received oral topical (eg, gel or patch), intranasal, or buccal T therapy within the
             previous 2 weeks, intramuscular T injection of short-acting duration (eg, T enanthate,
             T cypionate) within the previous 4 weeks, intramuscular T injection of long-acting
             duration (eg, AVEED) within the previous 20 weeks, or T implantable pellets
             (Testopel®) within the previous 6 months.

          2. Has an intercurrent disease deemed clinically significant in the opinion of the
             investigator of any type; in particular, liver, kidney, uncontrolled or poorly
             controlled heart disease, including hypertension, congestive heart failure or coronary
             heart disease, or psychiatric-illness, including severe depression.

          3. Has had a recent (within 2 years) history of stroke, transient ischemic attack, or
             acute coronary event.

          4. Has a mean of the triplicate assessment of sBP > 150 mm Hg and/or dBP > 90 mm Hg at
             screening (if prescribed antihypertensives, subject should be taking medications on
             the day of the screening visit with a sip of water). Subjects < 60 years of age and
             prescribed antihypertensives will be excluded if the mean of the triplicate assessment
             of sBP > 140 mm Hg and/or dBP > 90 mm Hg at screening.

          5. Has had recent (within 2 years) history of angina or stent (coronary or carotid)
             placement.

          6. Has untreated, severe obstructive sleep apnea.

          7. Has clinically significant abnormal laboratory values, including serum transaminases >
             2 × upper limits of normal (ULN), serum bilirubin > 1.5 × ULN and serum creatinine >
             1.5 × ULN.

          8. Has a hematocrit (HCT) value of < 35% or > 48%.

          9. Has a history of polycythemia, either idiopathic or associated with TRT treatment.

         10. Is a diabetic subject with a glycosylated hemoglobin > 8.5%.

         11. Has a body mass index (BMI) ≥ 38 kg/m2.

         12. Has been on stable doses of antihypertensive medication for < 3 months.

         13. Has an abnormal prostate digital rectal examination [(DRE); palpable nodules],
             elevated PSA (serum PSA > 4.0 ng/mL), I-PSS > 19 points at screening, and/or history
             of, or current or suspected, prostate cancer.

         14. Has a history of, or current or suspected, breast cancer.

         15. Has a history of abnormal bleeding tendencies or thrombophlebitis unrelated to
             venipuncture or intravenous cannulation within the previous 2 years.

         16. Use of dietary supplements such as saw palmetto or phytoestrogens and any dietary
             supplements that may increase total T, such as androstenedione or
             dehydroepiandrosterone within the previous 4 weeks.

         17. Has known malabsorption syndrome and/or current treatment with oral lipase inhibitors
             (eg, orlistat [Xenical®]) and/or bile acid-binding resins (eg, cholestyramine
             [Questran®], colestipol [Colestid®]) or treatments that promote gastric emptying (eg,
             metoclopramide [Reglan®]).

         18. Inability to observe all rules and smoking restrictions in place at the clinical
             facility during confinement.

         19. Has history of abuse of alcohol or any drug substance within the previous 2 years.

         20. Poor compliance or unlikely to keep clinic appointments and remain for entire
             confinement period.

         21. Has received any drug as part of another research study within 30 days of initial dose
             administration in this study.

         22. Donated blood (≥ 500 mL) within the 12-week period before the initial study dose.

         23. Current use of the following groups of drugs that effect T levels, T metabolism or
             levels of T metabolites, namely antiandrogens, 5-alpha-reductase inhibitors (eg,
             dutasteride, finasteride), estrogens, long-acting opioid analgesics (eg, methadone
             hydrochloride, buprenorphine hydrochloride) or human growth hormone (HGH).

         24. Unwilling or unable to follow the dietary requirements for this study.