Efficacy and Safety of Oral Testosterone Undecanoate in Hypogonadal Men
Condition: Hypogonadism, Male
MeSH terms: Hypogonadism; Eunuchism
Intervention: SOV2012-F1; AndroGel
Intervention description: oral preparation of testosterone undecanoate (TU); topical testosterone gel 1.62%
Intervention MeSH terms: Testosterone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Masking description: Open label
Enrollment: 314.0
Sex: Male
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This will be a randomized, multicenter, open-label, active-controlled, efficacy, and safety
      study in adult hypogonadal men. The study duration is 12 months (365 days), including a
      90-day, open-label efficacy period and a 9-month (275-day) safety evaluation period.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male aged 18 to 65 years, inclusive, at the time of providing informed consent to
             participate in the study.

          2. Hypogonadism defined as having 2 consecutive serum total T levels≤ 281 ng/dL based on
             a blood sample, drawn at least 3 days apart, between 7 a.m. and 10 a.m.

          3. At least 1 clinical feature consistent with male hypogonadism. If a subject is
             receiving commercial TRT prior to Screening Visit 1, he must have a history of at
             least 1 clinical feature consistent with male hypogonadism.

          4. Must be naïve to androgen replacement therapy or washed out adequately of prior
             androgen replacement therapies; willing to cease current T treatment; or currently not
             taking any T treatment. Subjects must remain off all forms of T, except for dispensed
             study drug, throughout the entire study.

          5. No unstable ongoing concomitant medical conditions. Treated and well-controlled
             conditions such as type 2 diabetes, hypertension, or dyslipidemia are acceptable with
             stable medication in place for at least 3 months prior to study entry:

               1. Hemoglobin A1c ≤ 8.0%

               2. BP < 150/90 mm Hg

               3. Low-density lipoprotein cholesterol < 190 mg/dL.

          6. Subjects with an endocrine disorder requiring treatment other than hypogonadism must
             be on a stable dose of replacement medication for at least 3 months prior to study
             entry.

          7. Adequate venous access to allow collection of a number of blood samples via a venous
             cannula.

          8. Written informed consent to participate in the study and ability to comply with all
             study requirements.

        Exclusion Criteria:

          1. Serum PSA > 2.5 ng/ml and/or abnormal prostate gland on palpation, eg, palpable nodes,
             at Screening Visit 2.

          2. 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.

          3. Use of any drug that could interfere with measurement or assessment of serum androgen
             levels, including 5 alpha-reductase inhibitors, anabolic steroids, and drugs with
             antiandrogenic properties (eg, spironolactone, cimetidine, flutamide, bicalutamide,
             and ketoconazole). These drugs must be stopped for at least 1 month prior to study
             entry (6 months in the case of dutasteride). Patients taking potent, long-acting
             opiate therapy on a daily basis are not eligible for the study. Conversely, ad hoc use
             of potent, short-acting opiates for a period of less than 7 days may be permitted
             after discussion with the Marius Pharmaceuticals medical monitor.

          4. Use of over-the-counter products, including natural health products (eg, food
             supplements and herbal supplements such as saw palmetto or phytoestrogens) that may
             affect total T levels, within 7 days prior to study entry.

          5. History of drug or alcohol abuse within the past 2 years that in the opinion of the
             investigator could interfere with study participation and/or influence study efficacy
             and safety endpoints assessments.

          6. Unstable or chronic disease that could interfere with participation in the study or
             patient safety, including psychiatric disorders.

          7. Myocardial infarction, coronary artery surgery, heart failure, stroke, unstable
             angina, or other unstable cardiovascular disease within the past 6 months.

          8. Abnormal ECG considered clinically significant by investigator at Screening.

          9. Diagnosis of any cancer within the previous 5 years other than basal or squamous cell
             skin cancer with clear margins.

         10. Any surgical or medical condition that might alter administration of the study drug or
             comparator, including history of gastric surgery, cholecystectomy, vagotomy, bowel
             resection, or any surgical procedure that might interfere with gastrointestinal
             motility, pH, or absorption of TU.

         11. Duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months
             prior to screening.

         12. Chronic skin conditions on the chest or upper arms that would prevent administration
             of AndroGel in a manner designed to ensure reliable and consistent absorption thereof.

         13. Human immunodeficiency virus (HIV) infection.

         14. Chronic hepatitis B virus and/or hepatitis C virus (HCV) infection (as determined by
             positive testing for hepatitis B virus surface antigen or HCV antibody with
             confirmatory testing, ie, detectable serum HCV ribonucleic acid [RNA]).

         15. Clinically significant abnormal laboratory values at screening including but not
             limited to:

               1. Elevated liver enzymes (aspartate aminotransferase [AST], alanine
                  aminotransferase [ALT] > 2x upper limit of normal)

               2. Estimated glomerular filtration rate < 60 ml/min/1.73m2 as calculated by the
                  Modification of Diet in Renal Disease formula

               3. Hemoglobin < 11.0 g/dL or > 16.0 g/dL. For a subject previously on testosterone
                  replacement therapy with less than 30 days washout prior to screening Visit 2,
                  hemoglobin < 11.0 g/dL or > 17.0 g/dL.

         16. Severe and untreated obstructive sleep apnea syndrome.

         17. Severe lower urinary tract symptoms (American Urological Association/ IPSS ≥ 19).

         18. History of any clinically significant illness, infection, or surgical procedure within
             1 month prior to study entry.

         19. Past, current, or suspected prostate or breast cancer.

         20. History of long QT syndrome or unexplained sudden death in a first-degree relative
             (parent, sibling, or child).

         21. Concurrent treatment with medications that may impact the absorption, distribution,
             metabolism, or excretion of TU or place the subject at risk for treatment with T.

         22. Subject has a partner who is currently pregnant or planning pregnancy during the
             course of the study.

         23. Treatment with any other investigational drug within 30 days of study entry or > 5
             half-lives (whichever is longer) and at any time during the study.

         24. History of noncompliance to medical regimens or potential unreliability in the opinion
             of the investigator.

         25. Unwilling or unable to comply to the dietary requirements for this study.

         26. History of polycythemia, either idiopathic or associated with TRT.

         27. Donated blood (≥ 500 mL) within the 12-week period prior to study entry.

         28. History of an abnormal bleeding tendency or thrombophlebitis within the previous 2
             years that is not linked to venipuncture or intravenous cannulation.

         29. Onset of gynecomastia within the previous 6 months.

         30. For adrenocorticotropic hormone (ACTH) stimulation substudy only: Primary or secondary
             adrenal insufficiency.

         31. For Bioanalytical Sample Stability Substudy only: subjects with a hemoglobin less than
             13 g/dL at most recent assessment* [should be excluded].