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Efficacy and Safety of Oral Testosterone Undecanoate in Hypogonadal Men

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03198728
Recruitment Status : Recruiting
First Posted : June 26, 2017
Last Update Posted : June 21, 2019
Syneos Health
Information provided by (Responsible Party):
Marius Pharmaceuticals

Brief 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.

Condition or disease Intervention/treatment Phase
Hypogonadism, Male Drug: SOV2012-F1 Drug: AndroGel Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description: Open label
Primary Purpose: Treatment
Official Title: A 12-Month, Randomized, Active-controlled, Open-label Study of the Efficacy and Safety of Oral Testosterone Undecanoate in Hypogonadal Men (RE-TUne)
Actual Study Start Date : July 5, 2017
Estimated Primary Completion Date : October 25, 2019
Estimated Study Completion Date : May 31, 2020

Arm Intervention/treatment
Experimental: SOV2012-F1-treated

200 patients treated with SOV2012-F1, starting dose of 600 mg - (400 mg with morning meal and 200 mg with evening meal). Dose titrated up to a maximum of 600 mg TU in the morning and 400 mg in the evening or down to 200 mg TU in the morning based on plasma T at Days 14 and 42.

A further 170 patients treated with SOV-2012-F1 to support the ABPM sub study

Drug: SOV2012-F1
oral preparation of testosterone undecanoate (TU)

Active Comparator: Andro-Gel treated
100 patients treated with AndroGel, starting dose of 40.5 mg QD. Dose titrated down to 20.25 mg or up to 81 mg based on serum T on Days 14 and 42.
Drug: AndroGel
topical testosterone gel

Primary Outcome Measures :
  1. Efficacy of oral SOV2012-F1 by measuring the percentage of male hypogonadal subjects with average plasma total testosterone (T Cavg) within the normal range. [ Time Frame: 90 days ]
    Efficacy assessment includes T Cavg

Secondary Outcome Measures :
  1. maximum plasma testosterone concentration [ Time Frame: 90 days ]
    To determine the percentage of SOV2012-F1-treated subjects with maximum plasma testosterone concentration (T Cmax) values (a) < 1500 ng/dL; (b) 1800 to 2500 ng/dL; and (c) > 2500 ng/dL.

Other Outcome Measures:
  1. To determine changes from baseline in the IPSS [ Time Frame: 52 weeks ]
    Patient reported outcomes will be assessed by the International Prostate Symptom Score (I-PSS)

  2. To determine changes from baseline in the PDQ [ Time Frame: 52 weeks ]
    Patient reported outcomes will be assessed by the Psychosexual Daily Questionnaire (PDQ)

  3. To determine changes from baseline in the SF-36 [ Time Frame: 52 weeks ]
    Patient reported outcomes will be assessed by the Short-Form Survey (SF-36)

  4. To determine changes from baseline in the IIEF [ Time Frame: 52 weeks ]
    Patient reported outcomes will be assessed by the International Index of Erectile Function (IIEF)

  5. To determine change from baseline in fasting serum glucose concentration [ Time Frame: 52 weeks ]
  6. To determine change from baseline in fasting insulin concentration [ Time Frame: 52 weeks ]
  7. Incidence of AEs and SAEs leading withdrawal of drug [ Time Frame: 52 weeks ]
    To determine the incidence of adverse events (AEs), serious adverse events (SAEs), and AEs leading to study withdrawal in SOV2012-F1-treated subjects.

  8. Assess changes from baseline in blood pressure (BP) [ Time Frame: 52 weeks ]
  9. Assess changes from baseline in liver function tests [ Time Frame: 52 weeks ]
    Liver function tests (ALT, AST, total bilirubin, alkaline phosphatase).

  10. Assess changes from baseline in hematology parameters [ Time Frame: 52 weeks ]
    Hematology parameters (hemoglobin, hematocrit)

  11. Assess changes from baseline in hormone levels [ Time Frame: 52 weeks ]
    Hormone levels (luteinizing hormone [LH], follicle-stimulating hormone [FSH], dihydrotestosterone [DHT], sex hormone-binding globulin [SHBG], TSH).

  12. Assess changes from baseline in lipid profiles [ Time Frame: 52 weeks ]
    Lipid profiles (high and low-density lipoproteins, total cholesterol, triglycerides)

  13. Assess changes from baseline in PSA [ Time Frame: 52 weeks ]
    Serum prostate-specific antigen (PSA).

  14. Effect of SOV2012-F1 on adrenal cortical function as assessed by measuring the cortisol response to synthetic ACTH at baseline in subjects [ Time Frame: 52 weeks ]
    To determine the effect of SOV2012-F1 on adrenal cortical function as assessed by measuring the cortisol response to synthetic ACTH at baseline and after 52 weeks of treatment in a subset of SOV2012-F1 subjects.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No

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 < 12.5 g/dL.
  16. Hematocrit > 48%.
  17. Severe and untreated obstructive sleep apnea syndrome.
  18. Severe lower urinary tract symptoms (American Urological Association/ IPSS ≥ 19).
  19. History of seizures or convulsions, including febrile, alcohol, or drug withdrawal seizures.
  20. History of any clinically significant illness, infection, or surgical procedure within 1 month prior to study entry.
  21. Past, current, or suspected prostate or breast cancer.
  22. History of long QT syndrome or unexplained sudden death in a first-degree relative (parent, sibling, or child).
  23. 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.
  24. Subject has a partner who is currently pregnant or planning pregnancy during the course of the study.
  25. 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.
  26. History of noncompliance to medical regimens or potential unreliability in the opinion of the investigator.
  27. Unwilling or unable to comply to the dietary requirements for this study.
  28. History of polycythemia, either idiopathic or associated with TRT.
  29. Donated blood (≥ 500 mL) within the 12-week period prior to study entry.
  30. History of an abnormal bleeding tendency or thrombophlebitis within the previous 2 years that is not linked to venipuncture or intravenous cannulation.
  31. Onset of gynecomastia within the previous 6 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03198728

  Show 41 Study Locations
Sponsors and Collaborators
Marius Pharmaceuticals
Syneos Health
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Study Director: Alastair Smith, MB, ChB Syneos Health
Study Chair: Om Dhingra, PhD Marius Pharmaceuticals

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Responsible Party: Marius Pharmaceuticals Identifier: NCT03198728     History of Changes
Other Study ID Numbers: MRS-TU-2019
First Posted: June 26, 2017    Key Record Dates
Last Update Posted: June 21, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Gonadal Disorders
Endocrine System Diseases
Testosterone undecanoate
Testosterone enanthate
Testosterone 17 beta-cypionate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents