A Study of Oral Testosterone Undecanoate (TU) in Hypogonadal Men
Condition: Hypogonadism
MeSH terms: Hypogonadism
Intervention: Oral Testosterone Undecanoate; Axiron Testosterone Topical Solution
Intervention description: Subjects assigned to oral TU treatment will begin at 237 mg TU twice daily. Serial PK samples over 24 hours will be obtained after 21 days and 56 days of treatment. Dose adjustments may be made on Day 35 and Day 70, based on the T Cavg results obtained at Day 21 and Day 56, respectively. Dose will be increased if Cavg < 350 ng/dL, decreased if > 800 ng/dL and maintained if Cavg = 350 ng/dL to 800 ng/dL.; Subjects assigned to Axiron treatment will begin at 60 mg Axiron every morning. Axiron is applied to the axilla only.
Serial PK samples over 24 hours will be obtained after 21 days and 56 days of treatment. Dose adjustments may be made on Day 35 and Day 70, based on the T Cavg results obtained at Day 21 and Day 56, respectively. Dose will be increased if Cavg < 350 ng/dL, decreased if > 800 ng/dL and maintained if Cavg = 350 ng/dL to 800 ng/dL.
Intervention MeSH terms: Methyltestosterone; Pharmaceutical Solutions; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
Phase: Phase 3
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 222.0
Sex: Male
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      A Phase 3, Randomized, Active-controlled, Open-label Study of the Safety and Efficacy of Oral
      Testosterone Undecanoate (TU) in Hypogonadal Men
    

Eligibility criteria:

        Inclusion Criteria:

          1. Man 18 to 65 years of age, inclusive, with hypogonadism as defined by 2 AM total T
             values of <300 ng/dL drawn on 2 separate days ([approximately 7 days apart]).

          2. Adequate venous access

          3. Must be naïve to androgen-replacement therapy or washed out of prior androgen
             replacement therapies; willing to cease current T treatment or currently not be taking
             T treatment. 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. Voluntarily given written informed consent to participate in this study.

        Exclusion Criteria:

          1. Received oral topical, intranasal, or buccal T therapy within the previous 2 weeks,
             intramuscular T injection of short-acting duration within the previous 4 weeks,
             intramuscular T injection of long-acting duration within the previous 20 weeks, or T
             implantable pellets within the previous 6 months.

          2. Received oral TU in a previous Clarus-sponsored investigational study.

          3. Significant intercurrent disease 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.

          4. Recent (within 2 years) history of stroke, transient ischemic attack, or acute
             coronary event.

          5. A mean of the triplicate assessment of systolic blood pressure (sBP) > 150 mm Hg
             and/or diastolic blood pressure (dBP) > 90 mm Hg at screening.

          6. Recent (within 2 years) history of angina or stent (coronary or carotid) placement.

          7. Untreated, severe obstructive sleep apnea.

          8. Clinically significant abnormal laboratory values (serum transaminases > 2 × ULN,
             serum bilirubin > 1.5 × ULN and serum creatinine > 1.5 × ULN).

          9. Hematocrit (HCT) value of < 35% or > 48%.

         10. Has a history of polycythemia, either idiopathic or associated with testosterone
             replacement therapy (TRT).

         11. Glycosylated hemoglobin (A1C) > 8.5%.

         12. BMI ≥ 38 kg/m2.

         13. If receiving the following medications:

               -  Has been on stable doses of lipid-lowering medication for < 3 months;

               -  Has been on stable doses of oral medication for diabetes for < 2 months; or

               -  Has been on stable doses of antihypertensive medication for < 3 months.

         14. Abnormal prostate digital rectal examination (palpable nodules), elevated Prostate
             Specific Antigen (serum PSA > 4.0 ng/mL), International Prostate Symptom Score (I-PSS)
             > 19 points at screening, and/or history of, or current or suspected, prostate cancer.

         15. History of, or current or suspected, breast cancer.

         16. History of abnormal bleeding tendencies or thrombophlebitis unrelated to venipuncture
             or intravenous cannulation within the previous 2 years.

         17. 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.

         18. Known malabsorption syndrome and/or current treatment with oral lipase inhibitors and
             bile acid-binding resins.

         19. Inability to refrain from smoking during the confinement periods as required by the
             individual study center.

         20. History of alcohol abuse or any drug substance within the previous 2 years.

         21. Poor compliance or unlikely to keep clinic appointments.

         22. Has received any drug as part of another research study within 30 days of initial dose
             administration in this study.

         23. Donated blood (≥ 500 mL) within the 12-week period before the initial study dose.

         24. Currently uses antiandrogens, 5-alpha-reductase inhibitors, estrogens, potent oral
             CYP3A4 inducers, potent CYP3A4 inhibitors, or long acting opioid analgesics.

         25. Unwilling or unable to follow the dietary guidelines for this study, related to taking
             oral TU with meals that contain approximately 20 to 40 g of fat