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Efficacy and Safety of Oral Testosterone Undecanoate in Hypogonadal Men

Primary Purpose

Hypogonadism, Male

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
SOV2012-F1
AndroGel
Sponsored by
Marius Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypogonadism, Male

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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].

Sites / Locations

  • Central Research Associates, Inc.
  • Alabama Clinical Therapeutics, LLC
  • Coastal Clinical Research, Inc.
  • Quality of Life Medical and Research Centers, LLC
  • San Diego Sexual Medicine
  • South Florida Medical Research
  • PAB Clinical Research
  • Innovative Research of West Florida, Inc.
  • Jacksonville Impotence Treatment Center
  • Health Awareness, Inc.
  • Meridien Research
  • My Community Research Center
  • Oviedo Medical Research, LLC
  • Meridien Research
  • Primary Care Research Group
  • Northwest Clinical Trials
  • Advanced Clinical Research
  • Central Kentucky Research Associates
  • Centex Studies, Inc.
  • Men's Health Boston
  • Quality Clinical Research, Inc.
  • Palm Research Center, Inc.
  • Accumed Research Associates
  • Manhattan Medical Research Practice, PLLC
  • Rapha Institute For Clinical Research
  • Aventiv Research, Inc.
  • Urologic Consultants of SE Pennsylvania
  • Coastal Carolina Research Center
  • University Diabetes Endocrine Consultants
  • Centex Studies, Inc.
  • Pioneer Research Solutions, Inc.
  • Advanced Clinical Research
  • Clinical Research Associates of Tidewater
  • National Clinical Research, Inc.
  • Rainier Clinical Research Center, Inc.
  • Mid-Columbia Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

SOV2012-F1-treated

Andro-Gel™ treated

Arm Description

200 patients treated with SOV2012-F1, starting dose of 600 mg - (400 mg with morning meal and 200 mg with evening meal). Dose titrated on Days 28 and 56 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.

100 patients treated with AndroGel, starting dose of 40.5 mg QD. Dose titrated according to approved label, using samples from Days 14 and 42 and dose adjustments on Days 28 and 56.

Outcomes

Primary Outcome Measures

Percentage of Male Hypogonadal Subjects With Average NaF/EDTA Plasma Total Testosterone (T Cavg) Within the Normal Range Using Oral SOV2012-F1.
Efficacy assessment includes T Cavg calculated from NaF/EDTA plasma testosterone. The T Cavg is calculated as the 24-hour area under the curve (AUC), divided by 24, at Day 90, based on a fifteen blood samples (PK samples) taken over the 24-hours. The T concentration in each sample is measured using a validated LC-MS/MS method. The use of NaF/EDTA plasma tubes chilled after sample collection provides the most accurate values, as the prodrug TU may degrade post-sample collection, artificially inflating testosterone values.

Secondary Outcome Measures

Percentages of Participants in Each Category for Maximum Plasma Concentration
To determine the percentage of treated subjects with maximum plasma testosterone concentration (T Cmax) values (a) < 1.5X Upper Limit of Normal (ULN); (b) 1.8X to 2.5X ULN; and (c) > 2.5X ULN. For NaF/EDTA plasma, thresholds are 1200, 1440 and 2000 ng/dL of T. For serum, thresholds are 1500, 1800 and 2500 ng/dL of T. Note that the endpoint concerns only the investigational treatment SOV2012-F1 and the AndroGel results are reported for completeness. The reported percentages do not sum to 100% as the FDA criteria do not specify the percentage of subjects in the window of ≥ 1.5X and ≤ 1.8X the ULN.

Full Information

First Posted
June 21, 2017
Last Updated
June 6, 2023
Sponsor
Marius Pharmaceuticals
Collaborators
Syneos Health
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1. Study Identification

Unique Protocol Identification Number
NCT03198728
Brief Title
Efficacy and Safety of Oral Testosterone Undecanoate in Hypogonadal Men
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
July 5, 2017 (Actual)
Primary Completion Date
May 1, 2020 (Actual)
Study Completion Date
May 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Marius Pharmaceuticals
Collaborators
Syneos Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. 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.
Detailed Description
MRS-TU-2019 was a 12-month study designed to determine the efficacy of oral SOV2012-F1 as measured by the percentage of male hypogonadal subjects with average total testosterone (T Cavg) in plasma within the normal range after 90 days of treatment. This study included an AndroGel™ arm as a safety comparator; after the 90-day efficacy period, dosing continued for 9 additional months in both arms to gather safety data. This study also examined the percentage of SOV2012-F1-treated subjects with maximum total testosterone (Cmax) in plasma values after 90 days of treatment: a. ≤1.5 X upper limit of normal (ULN); b. 1.8 X ULN to 2.5 X ULN' and c. >2.5 X ULN. The study also included an adrenal cortical function substudy conducted in 30 SOV2012-F1 subjects and 15 AndroGel subjects. Four patient-reported outcome measures were also used during the study: IPSS, PDQ, SF-36 and IIEF.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogonadism, Male

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Masking Description
Open label
Allocation
Randomized
Enrollment
314 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SOV2012-F1-treated
Arm Type
Experimental
Arm Description
200 patients treated with SOV2012-F1, starting dose of 600 mg - (400 mg with morning meal and 200 mg with evening meal). Dose titrated on Days 28 and 56 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.
Arm Title
Andro-Gel™ treated
Arm Type
Active Comparator
Arm Description
100 patients treated with AndroGel, starting dose of 40.5 mg QD. Dose titrated according to approved label, using samples from Days 14 and 42 and dose adjustments on Days 28 and 56.
Intervention Type
Drug
Intervention Name(s)
SOV2012-F1
Intervention Description
oral preparation of testosterone undecanoate (TU)
Intervention Type
Drug
Intervention Name(s)
AndroGel
Intervention Description
topical testosterone gel 1.62%
Primary Outcome Measure Information:
Title
Percentage of Male Hypogonadal Subjects With Average NaF/EDTA Plasma Total Testosterone (T Cavg) Within the Normal Range Using Oral SOV2012-F1.
Description
Efficacy assessment includes T Cavg calculated from NaF/EDTA plasma testosterone. The T Cavg is calculated as the 24-hour area under the curve (AUC), divided by 24, at Day 90, based on a fifteen blood samples (PK samples) taken over the 24-hours. The T concentration in each sample is measured using a validated LC-MS/MS method. The use of NaF/EDTA plasma tubes chilled after sample collection provides the most accurate values, as the prodrug TU may degrade post-sample collection, artificially inflating testosterone values.
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Percentages of Participants in Each Category for Maximum Plasma Concentration
Description
To determine the percentage of treated subjects with maximum plasma testosterone concentration (T Cmax) values (a) < 1.5X Upper Limit of Normal (ULN); (b) 1.8X to 2.5X ULN; and (c) > 2.5X ULN. For NaF/EDTA plasma, thresholds are 1200, 1440 and 2000 ng/dL of T. For serum, thresholds are 1500, 1800 and 2500 ng/dL of T. Note that the endpoint concerns only the investigational treatment SOV2012-F1 and the AndroGel results are reported for completeness. The reported percentages do not sum to 100% as the FDA criteria do not specify the percentage of subjects in the window of ≥ 1.5X and ≤ 1.8X the ULN.
Time Frame
90 days
Other Pre-specified Outcome Measures:
Title
Change From Baseline in the IPSS
Description
Patient reported outcomes will be assessed by the International Prostate Symptom Score (I-PSS) Reporting a score on a scale 0 to 35 (asymptomatic to very symptomatic). Mean change from baseline is reported and is the difference between the score at Baseline (pre-treatment) and at Day 90 and Day 365. Thus, a positive value at Day 90 or Day 365 represents an increase in the score from baseline.
Time Frame
Baseline (pre-treatment) to 90 days and 365 days
Title
Change From Baseline in the Psychosexual Daily Questionnaire (PDQ)
Description
Patient reported outcomes are 7-day average score at baseline, and average change from baseline (CfB) at Day 90 and Day 365. Weekly daily average scores calculated for diaries completed at least 3 of 7 days. The three domains are: Sexual desire subscale 0=None, 1=very low to 7=Very High. Sexual enjoyment with/without partner subscale 0=None to 7=Very high enjoyment/pleasure. Partner availability not used in scoring. Positive CfB desirable. Positive and negative mood subscales 0=Not at all true to 7=Very true (Likert 7-point scale, 7-day average reported). Positive mood (sum of 4 questions) score range = 0 to 28; positive changes from baseline desirable. Negative mood (sum of 5 questions) score range = 0 to 35; negative CfB desirable. Weekly sexual activity subscale score is 7*(# of activities per week / # of days reported). Percent full erection uses scale of 0-100% (10% steps). Satisfaction with erection 0=not satisfactory to 7=very satisfactory. Positive CfB desirable.
Time Frame
Baseline (pre-treatment) to 90 days and 365 days
Title
Change From Baseline in the SF-36
Description
Patient reported outcomes assessed by the Short-Form Survey (SF-36). This scale assesses 8 health concepts: limitations in physical activities because of health problems limitations in social activities because of physical or emotional problems limitations in usual role activities because of physical health problems bodily pain general mental health (psychological distress and well-being) limitations in usual role activities because of emotional problems vitality (energy and fatigue) general health perceptions. Each domain is scored from 0-100 with a score of 0 = maximum disability and a score of 100 = no disability. End of Treatment (EOT) occurred either at time of early withdrawal from the study or at Day 365. The reported value is the change from baseline. A positive value at EOT indicates improvement in the measure towards less disability. The EOT Change from Baseline is simply the arithmetic difference between the Baseline and EOT scores.
Time Frame
Baseline (Day 1, pre-treatment) and change from baseline at the End of Treatment (EOT)
Title
Change From Baseline in the IIEF
Description
Patient reported outcomes are assessed by the International Index of Erectile Function (IIEF). A score of 0-5 (higher score indicating improvement) is awarded to each of the 15 questions that examine overall satisfaction (2 questions, total possible score=10), and the 4 main domains of male sexual function: erectile function (6 questions, total possible score=30), orgasmic function (2 questions, total possible score=10), sexual desire (2 questions, total possible score=10), and intercourse satisfaction (3 questions, total possible score=15). The IIEF results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at the End of Treatment (EOT). EOT occurred either at time of early withdrawal from the study or at Day 365. The reported value is the change from baseline. A positive value at EOT indicates improvement in the measure. The EOT Change from Baseline is simply the arithmetic difference between the Baseline and End of Treatment scores.
Time Frame
Baseline (Day 1, pre-treatment) and change from baseline at the End of Treatment (EOT)
Title
Change From Baseline in Fasting Serum Glucose (FSG) Concentration
Description
The measured value is the FSG concentration reported as mg/dL. The FSG results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The reported value is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and measured values.
Time Frame
Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.
Title
Change From Baseline in Fasting Insulin Concentration
Description
The measured value is the insulin concentration reported as in units of uU/mL. The insulin results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The reported value is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and measured values.
Time Frame
Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.
Title
Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel
Description
Changes from baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), as mmHg. The blood pressure results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The reported value is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value. A positive value for Change in Baseline represents an increase in the measured SBP or DBP.
Time Frame
Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.
Title
Change From Baseline in Liver Function Tests
Description
Liver function tests (ALT, AST, total bilirubin, alkaline phosphatase). The liver function test results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The reported value is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value. A positive value for Change in Baseline represents an increase in the liver function test value
Time Frame
Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.
Title
Change in Bilirubin
Description
Change in bilirubin from Baseline The bilirubin test results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The reported value is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value. A positive value for Change in Baseline represents an increase in the bilirubin value.
Time Frame
Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.
Title
Change From Baseline in Hematology Parameters
Description
Hematology parameters (HbA1c) with diabetes mellitus and Without diabetes mellitus. The HbA1c test results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The reported value at End of Treatment is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and the End of Treatment value. Normal range for HbA1c is 4 to 5.6%, pre-diabetic is 5.7 to 6.4%, and diabetic is equal to or greater than 6.5%.
Time Frame
Baseline (Day 1, pre-treatment) and the change from baseline at the End of Treatment
Title
Change From Baseline in Hormone Levels
Description
Hormone levels (luteinizing hormone [LH], follicle-stimulating hormone [FSH], sex hormone-binding globulin [SHBG], TSH). The hormone level test results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value at Day 90 or Day 365. A positive value for Change in Baseline represents an increase in the hormone level.
Time Frame
Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment
Title
Change in Hormone SHBG
Description
Change in hormone Sex Hormone Binding Globulin (SHBG). The hormone level test results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value at Day 90 or Day 365. A positive value for Change in Baseline represents an increase in the hormone level.
Time Frame
Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment
Title
Change in TSH (Thyrotropin)
Description
Change from Baseline in Thyroid stimulating Hormone (TSH). The TSH test results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value at Day 90 or Day 365. A positive value for Change in Baseline represents an increase in the TSH level.
Time Frame
Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment
Title
Change From Baseline in Lipid Profiles
Description
Lipid profiles (high and low-density lipoproteins, total cholesterol, triglycerides). The lipid test results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270, Day 365 and the End of Treatment. End of Treatment occurred either at time of early withdrawal from the study or at Day 365. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value. A positive value for Change in Baseline represents an increase in the lipid value.
Time Frame
Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270, Day 365 and the End of Treatment
Title
Change From Baseline in PSA
Description
Serum prostate-specific antigen (PSA). The PSA results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270, Day 365 and the End of Treatment. End of Treatment occurred either at time of early withdrawal from the study or at Day 365. The reported value is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value. A positive value for Change in Baseline represents an increase in the PSA value.
Time Frame
Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270, Day 365 and the End of Treatment
Title
Effect of SOV2012-F1 on Adrenal Cortical Function as Assessed by Measuring the Cortisol Response to Synthetic ACTH at Baseline in Subjects
Description
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. . The sample size was calculated based on a assumed common Standard Deviation of 93 nmol/L to yield a half-width of not more than 60 nmol/L; hence a sample size of 30 was targeted for the investigational (SOV2012-F1) arm, and 15 for the safety control arm (AndroGel).
Time Frame
52 weeks

10. Eligibility

Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male aged 18 to 65 years, inclusive, at the time of providing informed consent to participate in the study. 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. 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. 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. 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: Hemoglobin A1c ≤ 8.0% BP < 150/90 mm Hg Low-density lipoprotein cholesterol < 190 mg/dL. 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. Adequate venous access to allow collection of a number of blood samples via a venous cannula. Written informed consent to participate in the study and ability to comply with all study requirements. Exclusion Criteria: Serum PSA > 2.5 ng/ml and/or abnormal prostate gland on palpation, eg, palpable nodes, at Screening Visit 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. 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. 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. 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. Unstable or chronic disease that could interfere with participation in the study or patient safety, including psychiatric disorders. Myocardial infarction, coronary artery surgery, heart failure, stroke, unstable angina, or other unstable cardiovascular disease within the past 6 months. Abnormal ECG considered clinically significant by investigator at Screening. Diagnosis of any cancer within the previous 5 years other than basal or squamous cell skin cancer with clear margins. 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. Duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to screening. 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. Human immunodeficiency virus (HIV) infection. 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]). Clinically significant abnormal laboratory values at screening including but not limited to: Elevated liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] > 2x upper limit of normal) Estimated glomerular filtration rate < 60 ml/min/1.73m2 as calculated by the Modification of Diet in Renal Disease formula 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. Severe and untreated obstructive sleep apnea syndrome. Severe lower urinary tract symptoms (American Urological Association/ IPSS ≥ 19). History of any clinically significant illness, infection, or surgical procedure within 1 month prior to study entry. Past, current, or suspected prostate or breast cancer. History of long QT syndrome or unexplained sudden death in a first-degree relative (parent, sibling, or child). 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. Subject has a partner who is currently pregnant or planning pregnancy during the course of the study. 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. History of noncompliance to medical regimens or potential unreliability in the opinion of the investigator. Unwilling or unable to comply to the dietary requirements for this study. History of polycythemia, either idiopathic or associated with TRT. Donated blood (≥ 500 mL) within the 12-week period prior to study entry. History of an abnormal bleeding tendency or thrombophlebitis within the previous 2 years that is not linked to venipuncture or intravenous cannulation. Onset of gynecomastia within the previous 6 months. For adrenocorticotropic hormone (ACTH) stimulation substudy only: Primary or secondary adrenal insufficiency. For Bioanalytical Sample Stability Substudy only: subjects with a hemoglobin less than 13 g/dL at most recent assessment* [should be excluded].
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alastair Smith, MB, ChB
Organizational Affiliation
Syneos Health
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Om Dhingra, PhD
Organizational Affiliation
Marius Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
Central Research Associates, Inc.
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35205
Country
United States
Facility Name
Alabama Clinical Therapeutics, LLC
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35235
Country
United States
Facility Name
Coastal Clinical Research, Inc.
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
Facility Name
Quality of Life Medical and Research Centers, LLC
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85712
Country
United States
Facility Name
San Diego Sexual Medicine
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
Facility Name
South Florida Medical Research
City
Aventura
State/Province
Florida
ZIP/Postal Code
33180
Country
United States
Facility Name
PAB Clinical Research
City
Brandon
State/Province
Florida
ZIP/Postal Code
33511
Country
United States
Facility Name
Innovative Research of West Florida, Inc.
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33756
Country
United States
Facility Name
Jacksonville Impotence Treatment Center
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32223
Country
United States
Facility Name
Health Awareness, Inc.
City
Jupiter
State/Province
Florida
ZIP/Postal Code
33458
Country
United States
Facility Name
Meridien Research
City
Lakeland
State/Province
Florida
ZIP/Postal Code
33805
Country
United States
Facility Name
My Community Research Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Oviedo Medical Research, LLC
City
Oviedo
State/Province
Florida
ZIP/Postal Code
32765
Country
United States
Facility Name
Meridien Research
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33709
Country
United States
Facility Name
Primary Care Research Group
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30312
Country
United States
Facility Name
Northwest Clinical Trials
City
Boise
State/Province
Idaho
ZIP/Postal Code
83704
Country
United States
Facility Name
Advanced Clinical Research
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
Facility Name
Central Kentucky Research Associates
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40509
Country
United States
Facility Name
Centex Studies, Inc.
City
Lake Charles
State/Province
Louisiana
ZIP/Postal Code
70601
Country
United States
Facility Name
Men's Health Boston
City
Chestnut Hill
State/Province
Massachusetts
ZIP/Postal Code
02467
Country
United States
Facility Name
Quality Clinical Research, Inc.
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Palm Research Center, Inc.
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89148
Country
United States
Facility Name
Accumed Research Associates
City
Garden City
State/Province
New York
ZIP/Postal Code
11530
Country
United States
Facility Name
Manhattan Medical Research Practice, PLLC
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Rapha Institute For Clinical Research
City
Fayetteville
State/Province
North Carolina
ZIP/Postal Code
28314
Country
United States
Facility Name
Aventiv Research, Inc.
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43213
Country
United States
Facility Name
Urologic Consultants of SE Pennsylvania
City
Bala-Cynwyd
State/Province
Pennsylvania
ZIP/Postal Code
19004
Country
United States
Facility Name
Coastal Carolina Research Center
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
Facility Name
University Diabetes Endocrine Consultants
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37411
Country
United States
Facility Name
Centex Studies, Inc.
City
Houston
State/Province
Texas
ZIP/Postal Code
77058
Country
United States
Facility Name
Pioneer Research Solutions, Inc.
City
Houston
State/Province
Texas
ZIP/Postal Code
77099
Country
United States
Facility Name
Advanced Clinical Research
City
West Jordan
State/Province
Utah
ZIP/Postal Code
84088
Country
United States
Facility Name
Clinical Research Associates of Tidewater
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
National Clinical Research, Inc.
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23294
Country
United States
Facility Name
Rainier Clinical Research Center, Inc.
City
Renton
State/Province
Washington
ZIP/Postal Code
98057
Country
United States
Facility Name
Mid-Columbia Research
City
Richland
State/Province
Washington
ZIP/Postal Code
99352
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://clinicaltrials.gov/ct2/show/NCT04467697
Description
MRS-TU-2019EXT study
URL
http://online.liebertpub.com/doi/10.1089/andro.2022.0011
Description
Effects of Oral Testosterone Undecanoate (Kyzatrex) Versus Testosterone Gel (Androgel) on Long-Term (to 12 months) Blood Pressure Levels

Learn more about this trial

Efficacy and Safety of Oral Testosterone Undecanoate in Hypogonadal Men

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