A Phase 4 Study to Evaluate Adrenal Function in Hypogonadal Men Treated With JATENZO® for 12 Months

TOL-CLAR-20024 is a Phase 4, multi-center, open-label safety study evaluating the potential effect of JATENZO on adrenal function in hypogonadal men treated with JATENZO for 12 months.

Following all screening activities and confirmation that the subject has met all eligibility requirements, JATENZO treatment for approximately 1 year will begin. The dose of JATENZO will be titrated using its standard dose-titration algorithms based on serum testosterone levels. The Treatment Period will consist of Visits 1 - 12, with cosyntropin stimulation test completed at Visit 9 (Day 169 ±7) and Visit 12 (Day 365 ±7). At each visit during the Treatment Period, subjects will be evaluated for signs and symptoms of adrenal insufficiency, occurrence of adverse events, and changes in concomitant medications. There will be a safety follow-up visit 2 weeks after completion of Visit 12.

Eligibility Criteria:
Inclusion Criteria:

1. Subject must be a man 18 to 65 years of age, inclusive, with a previous clinical diagnosis of hypogonadism (signs/symptoms consistent with hypogonadism and a low T level as defined by established criteria at the time of diagnosis); subjects must also have at least 1 T level \< 300 ng/dL at either Screen 1 or Screen 2.
2. Subject must be naïve to androgen replacement therapy or washed out of prior androgen replacement therapies (wash out durations specified in exclusion criterion); that is, be willing to cease current T treatment, or currently not be taking T treatment.
3. Subject agrees as part of signed informed consent to remain off all forms of T, except for dispensed study drug, throughout the entire study.
4. Subject must have adequate venous access in the left or right arm to allow collection of blood samples.
5. Subject must be able and willing to provide written informed consent and comply with the trial protocol and procedures.

Exclusion Criteria:

* Subject will be excluded if 1 or more of the main exclusion is applicable:

  1. Subject with a history of panhypopituitarism or multiple endocrine deficiencies (whether or not on stable doses of thyroid hormone and adrenal replacement hormones).
  2. Subject with a current or prior history of AI.
  3. Subject is currently receiving corticosteroids.
  4. On the CST at Screen 3, the maximum serum total cortisol at both the 30- and 60-minute timepoint is ≤ 14 mcg/dL or has a baseline CBG outside the reference range.
  5. Subject with a history of a short course (2 weeks or less) of any glucocorticoids within the past 3 months or anabolic steroids other than testosterone within the past 6 months.
  6. Subject with a history of a protracted course of any glucocorticoid therapy (e.g., inhaled nasal steroids, inhaled oral steroids, topical steroids, injectable steroids such as joint injections) or anabolic steroids other than T. Enrolled subjects who take glucocorticoids while on study drug may be discontinued from the study at the discretion of the investigator in consultation with the sponsor.
  7. Subject with a history of anabolic steroid abuse.
  8. Subject with a diagnosis of hypogonadism who has received any topical (e.g., gel or patch), intranasal, or buccal T therapy within the previous 2 weeks, intramuscular T injection of short-acting duration (e.g., T enanthate, T cypionate) within the previous 4 weeks, intramuscular T injection of long-acting duration (e.g., AVEED®) within the previous 20 weeks, T implantable pellets (Testopel®) product within the previous 6 months or any prior use of an oral testosterone product.
  9. Subject has received any drug as part of another research study within 30 days of initial dose administration in this study.
  10. Subject has significant intercurrent disease (e.g., liver, kidney, inflammatory bowel disease, uncontrolled or poorly controlled heart disease, including hypertension, thromboembolism, congestive heart failure, or coronary heart disease, psychiatric illness, including severe depression), which in the opinion of the Investigator, would affect study participation or interpretation of study assessments.
  11. Subject has untreated, severe obstructive sleep apnea.
  12. Subject has clinically significant abnormal laboratory values, including serum transaminases \> 2 × upper limits of normal (ULN), serum bilirubin \> 1.5 × ULN (except subjects with Gilbert syndrome) and serum creatinine \> 1.5 × ULN.
  13. Subject has a HCT value of \< 35% or \> 50%.
  14. Subject has a history of polycythemia, either idiopathic or associated with TRT treatment.
  15. Subject is diabetic with a glycosylated hemoglobin \> 8.5%.
  16. Subject has a body mass index (BMI) ≥ 38 kg/m2.
  17. Subject has had a recent (within 2 years) history of stroke, transient ischemic attack, or acute coronary event.
  18. Subject has a mean (triplicate assessments) systolic blood pressure (sBP) \> 140 mm Hg and/or diastolic blood pressure (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).
  19. Subject has had recent (within 2 years) history of angina or stent (coronary or carotid) placement.
  20. Subject does not meet the requirements for concomitant medication as outlined below:

      1. If hypertensive, on a stable dose of antihypertensive medication for \< 3 months
      2. If diabetic, on a stable dose of oral medication for \< 2 months
      3. If on anticonvulsant therapy, on a stable dose for \< 3 months
      4. If on lipid lowering medications, on a stable dose for \< 3 months. Subject is expected to remain on a stable dose of lipid-lowering medication(s) throughout the study.
  21. Subject has an abnormal prostate DRE (palpable nodules), elevated PSA (serum PSA \> 4.0 ng/mL), I-PSS \> 19 points at screening.
  22. Subject has a history of, or current or suspected prostate cancer.
  23. Subject has a history of, or current or suspected breast cancer.
  24. Subject currently using a drug known to affect T levels, T metabolism or levels of T metabolites. These include: 5-alpha-reductase inhibitors (e.g., dutasteride, finasteride), estrogens, long-acting opioid analgesics (e.g., methadone hydrochloride, buprenorphine hydrochloride), human growth hormone (HGH) or over-the-counter supplements purported to "boost" testosterone, sexual function or improve prostate symptoms.
  25. Subject 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.
  26. Subject use of any over-the-counter "adrenal supplements".
  27. Subject is not willing to stop all supplemental biotin 3 days prior to testing at intervals described in this protocol.
  28. Subject currently using Megace, atypical anti-psychotics (e.g., clozapine, aripiorazole, asenapine, lumateperone, olanzapine, paliperidone, aripiprazole, ziprasidone, cariprazine, risperidone, pimavanserin, ioperidone, brexpiprazole, lurasidone, quetiapine) or chronic benzodiazepine use.
  29. Subject has a history of abnormal bleeding tendencies or thrombophlebitis unrelated to venipuncture or intravenous cannulation within the previous 2 years.
  30. Subject has history of abuse of alcohol or any drug substance within the previous 2 years.
  31. Subject deemed to be a compliance risk or unlikely to keep clinic appointments.
  32. Subject donated blood (≥ 500 mL) within the 12-week period before the initial study dose.