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Efficacy and Safety of Oral Testosterone Undecanoate in Hypogonadal Men

Sponsor
Marius Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03198728
Collaborator
Syneos Health (Other)
314
Enrollment
36
Locations
2
Arms
33.9
Actual Duration (Months)
8.7
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
314 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 :
Jul 5, 2017
Actual Primary Completion Date :
May 1, 2020
Actual Study Completion Date :
May 1, 2020

Arms and Interventions

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.

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

Outcome Measures

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. [90 days]

    Efficacy assessment includes T Cavg

Secondary Outcome Measures

  1. maximum plasma testosterone concentration [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 [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 [52 weeks]

    Patient reported outcomes will be assessed by the Psychosexual Daily Questionnaire (PDQ)

  3. To determine changes from baseline in the SF-36 [52 weeks]

    Patient reported outcomes will be assessed by the Short-Form Survey (SF-36)

  4. To determine changes from baseline in the IIEF [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 [52 weeks]

  6. To determine change from baseline in fasting insulin concentration [52 weeks]

  7. Incidence of AEs and SAEs leading withdrawal of drug [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) [52 weeks]

  9. Assess changes from baseline in liver function tests [52 weeks]

    Liver function tests (ALT, AST, total bilirubin, alkaline phosphatase).

  10. Assess changes from baseline in hematology parameters [52 weeks]

    Hematology parameters (hemoglobin, hematocrit)

  11. Assess changes from baseline in hormone levels [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 [52 weeks]

    Lipid profiles (high and low-density lipoproteins, total cholesterol, triglycerides)

  13. Assess changes from baseline in PSA [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
Male
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:

  6. Hemoglobin A1c ≤ 8.0%

  7. BP < 150/90 mm Hg

  8. Low-density lipoprotein cholesterol < 190 mg/dL.

  9. 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.

  10. Adequate venous access to allow collection of a number of blood samples via a venous cannula.

  11. 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:

  16. Elevated liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] > 2x upper limit of normal)

  17. Estimated glomerular filtration rate < 60 ml/min/1.73m2 as calculated by the Modification of Diet in Renal Disease formula

  18. 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.

  19. Severe and untreated obstructive sleep apnea syndrome.

  20. Severe lower urinary tract symptoms (American Urological Association/ IPSS ≥ 19).

  21. History of any clinically significant illness, infection, or surgical procedure within 1 month prior to study entry.

  22. Past, current, or suspected prostate or breast cancer.

  23. History of long QT syndrome or unexplained sudden death in a first-degree relative (parent, sibling, or child).

  24. 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.

  25. Subject has a partner who is currently pregnant or planning pregnancy during the course of the study.

  26. 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.

  27. History of noncompliance to medical regimens or potential unreliability in the opinion of the investigator.

  28. Unwilling or unable to comply to the dietary requirements for this study.

  29. History of polycythemia, either idiopathic or associated with TRT.

  30. Donated blood (≥ 500 mL) within the 12-week period prior to study entry.

  31. History of an abnormal bleeding tendency or thrombophlebitis within the previous 2 years that is not linked to venipuncture or intravenous cannulation.

  32. Onset of gynecomastia within the previous 6 months.

  33. For adrenocorticotropic hormone (ACTH) stimulation substudy only: Primary or secondary adrenal insufficiency.

  34. For Bioanalytical Sample Stability Substudy only: subjects with a hemoglobin less than 13 g/dL at most recent assessment* [should be excluded].

Contacts and Locations

Locations

Site City State Country Postal Code
1 Central Research Associates, Inc. Birmingham Alabama United States 35205
2 Alabama Clinical Therapeutics, LLC Birmingham Alabama United States 35235
3 Coastal Clinical Research, Inc. Mobile Alabama United States 36608
4 Quality of Life Medical and Research Centers, LLC Tucson Arizona United States 85712
5 San Diego Sexual Medicine San Diego California United States 92120
6 South Florida Medical Research Aventura Florida United States 33180
7 PAB Clinical Research Brandon Florida United States 33511
8 Innovative Research of West Florida, Inc. Clearwater Florida United States 33756
9 Jacksonville Impotence Treatment Center Jacksonville Florida United States 32223
10 Health Awareness, Inc. Jupiter Florida United States 33458
11 Meridien Research Lakeland Florida United States 33805
12 My Community Research Center Miami Florida United States 33155
13 Oviedo Medical Research, LLC Oviedo Florida United States 32765
14 Meridien Research Saint Petersburg Florida United States 33709
15 Primary Care Research Group Atlanta Georgia United States 30312
16 Northwest Clinical Trials Boise Idaho United States 83704
17 Advanced Clinical Research Meridian Idaho United States 83642
18 Central Kentucky Research Associates Lexington Kentucky United States 40509
19 Centex Studies, Inc. Lake Charles Louisiana United States 70601
20 Men's Health Boston Chestnut Hill Massachusetts United States 02467
21 Quality Clinical Research, Inc. Omaha Nebraska United States 68114
22 Palm Research Center, Inc. Las Vegas Nevada United States 89148
23 Accumed Research Associates Garden City New York United States 11530
24 Manhattan Medical Research Practice, PLLC New York New York United States 10016
25 Rapha Institute For Clinical Research Fayetteville North Carolina United States 28314
26 Aventiv Research, Inc. Columbus Ohio United States 43213
27 Urologic Consultants of SE Pennsylvania Bala-Cynwyd Pennsylvania United States 19004
28 Coastal Carolina Research Center Mount Pleasant South Carolina United States 29464
29 University Diabetes Endocrine Consultants Chattanooga Tennessee United States 37411
30 Centex Studies, Inc. Houston Texas United States 77058
31 Pioneer Research Solutions, Inc. Houston Texas United States 77099
32 Advanced Clinical Research West Jordan Utah United States 84088
33 Clinical Research Associates of Tidewater Norfolk Virginia United States 23507
34 National Clinical Research, Inc. Richmond Virginia United States 23294
35 Rainier Clinical Research Center, Inc. Renton Washington United States 98057
36 Mid-Columbia Research Richland Washington United States 99352

Sponsors and Collaborators

  • Marius Pharmaceuticals
  • Syneos Health

Investigators

  • Study Director: Alastair Smith, MB, ChB, Syneos Health
  • Study Chair: Om Dhingra, PhD, Marius Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Marius Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03198728
Other Study ID Numbers:
  • MRS-TU-2019
First Posted:
Jun 26, 2017
Last Update Posted:
Jan 15, 2021
Last Verified:
Jan 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Hypogonadism
Eunuchism
Testosterone

Study Results

No Results Posted as of Jan 15, 2021