Efficacy and Safety of Oral Testosterone Undecanoate in H... | NCT03198728

Name	Class
Syneos Health	OTHER

Label	Type	Description	Intervention Names
SOV2012-F1-treated	Experimental	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.	Drug: SOV2012-F1
Andro-Gel™ treated	Active Comparator	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.	Drug: AndroGel

Name	Type	Description	Arm Group Labels	Other Names
SOV2012-F1	Drug	oral preparation of testosterone undecanoate (TU)	SOV2012-F1-treated

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	90 days

Secondary Outcomes

Measure	Description	Time Frame
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.

Other Outcomes

Measure	Description	Time Frame
Change From Baseline in the IPSS	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.

Eligibility Module

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:
1. Hemoglobin A1c ≤ 8.0%
2. BP < 150/90 mm Hg
3. 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:
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.
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].

Name	Affiliation	Role
Alastair Smith, MB, ChB	Syneos Health	Study Director
Om Dhingra, PhD	Marius Pharmaceuticals	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Central Research Associates, Inc.		Birmingham	Alabama	35205	United States
Alabama Clinical Therapeutics, LLC

PubMed Identifier	Type	Citation	Retractions
38606384	Derived	Bernstein JS, Dhingra OP. A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product. Ther Adv Urol. 2024 Apr 10;16:17562872241241864. doi: 10.1177/17562872241241864. eCollection 2024 Jan-Dec.

Label	URL
MRS-TU-2019EXT study	View source

ID	Title	Description
FG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 18, 2019	Feb 14, 2023

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000166

Secondary

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 Analysis Set

Posted

Number

percentage of actual number of subjects

90 days

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-gel™ Treated	100 patients treated with AndroGel, according to label, using sampling on Days 14 and 42 with dose adjustment on Days 28 and 65. AndroGel: topical testosterone gel, 1.62%

Other Pre-specified

Change From Baseline in the IPSS

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.

Full Analysis Set

Posted

Mean

Standard Deviation

score on a scale

Baseline (pre-treatment) to 90 days and 365 days

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-gel™ Treated	100 patients treated with AndroGel, according to label, using sampling on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Units	Counts

Other Pre-specified

Change From Baseline in the Psychosexual Daily Questionnaire (PDQ)

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.

Full Analysis Set

Posted

Mean

Standard Deviation

score on a scale

Baseline (pre-treatment) to 90 days and 365 days

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001

Other Pre-specified

Change From Baseline in the SF-36

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.

Full Analysis Set

Posted

Mean

Standard Deviation

score on a scale

Baseline (Day 1, pre-treatment) and change from baseline at the End of Treatment (EOT)

ID	Title	Description
OG000	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 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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001

Other Pre-specified

Change From Baseline in the IIEF

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.

Full Analysis Set

Posted

Mean

Standard Deviation

score on a scale

Baseline (Day 1, pre-treatment) and change from baseline at the End of Treatment (EOT)

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001

Other Pre-specified

Change From Baseline in Fasting Serum Glucose (FSG) Concentration

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.

Safety Set

Posted

Mean

Standard Deviation

mg/dL

Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-Gel™ Treated	100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Other Pre-specified

Change From Baseline in Fasting Insulin Concentration

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.

Safety Set

Posted

Mean

Standard Deviation

uU/mL

Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-Gel™ Treated	100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Other Pre-specified

Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel

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.

Safety Set

Posted

Mean

Standard Deviation

mmHg

Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-Gel™ Treated	100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Other Pre-specified

Change From Baseline in Liver Function Tests

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.

Safety set

Posted

Mean

Standard Deviation

U/L

Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-Gel™ Treated	100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Other Pre-specified

Change in Bilirubin

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.

Safety set

Posted

Mean

Standard Deviation

mg/dL

Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-Gel™ Treated	100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Other Pre-specified

Change From Baseline in Hematology Parameters

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%.

Safety Set

Posted

Mean

Standard Deviation

percentage of HbA1c

Baseline (Day 1, pre-treatment) and the change from baseline at the End of Treatment

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-Gel™ Treated	100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Other Pre-specified

Change From Baseline in Hormone Levels

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.

Safety set

Posted

Mean

Standard Deviation

mIU/mL

Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-Gel™ Treated	100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Other Pre-specified

Change in Hormone SHBG

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.

Safety Set

Posted

Mean

Standard Deviation

nmol/L

Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-Gel™ Treated	100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Other Pre-specified

Change in TSH (Thyrotropin)

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.

Safety Set

Posted

Mean

Standard Deviation

mU/L

Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-Gel™ Treated	100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Other Pre-specified

Change From Baseline in Lipid Profiles

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.

Safety Set LDL Cholesterol, Baseline = number of subjects with non-missing results

Posted

Mean

Standard Deviation

mg/dL

Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270, Day 365 and the End of Treatment

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-Gel™ Treated	100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Other Pre-specified

Change From Baseline in PSA

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.

Safety Set

Posted

Mean

Standard Deviation

ng/mL

Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270, Day 365 and the End of Treatment

ID	Title	Description
OG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-Gel™ Treated	100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Other Pre-specified

Effect of SOV2012-F1 on Adrenal Cortical Function as Assessed by Measuring the Cortisol Response to Synthetic ACTH at Baseline in Subjects

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).

ACTH Completers Set

Posted

Mean

Standard Deviation

nmol/L

52 weeks

ID	Title	Description
OG000	SOV2012-F1-Treated	The ACTH Substudy enrolled 29 patients out of 200 patients treated with SOV2012-F1, starting dose of 600 mg - (400 mg with morning meal and 200 mg with evening meal). Dose titrated (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
OG001	Andro-Gel™ Treated	The ACTH Substudy enrolled 13 participants out of the 100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Acute Myocardial infarction	Cardiac disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0010 events0 affected100 at risk
Atrial fibrillation	Cardiac disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0010 events0 affected100 at risk
Cardiac failure congestive	Cardiac disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0010 events0 affected100 at risk
Myocardial infarction	Cardiac disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0010 events0 affected100 at risk
Colitis	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0010 events0 affected100 at risk
Haemorrhoids	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0010 events0 affected100 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0002 events1 affected214 at risk EG0011 events1 affected100 at risk
Chest pain	General disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0010 events0 affected100 at risk
Cellulitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected214 at risk EG0010 events0 affected100 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0010 events0 affected100 at risk
Renal tubular acidosis	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0010 events0 affected100 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0010 events0 affected100 at risk
Finger amputation	Surgical and medical procedures	Systematic Assessment	EG0001 events1 affected214 at risk EG0010 events0 affected100 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG00020 events15 affected214 at risk EG00116 events12 affected100 at risk
Influenza	Infections and infestations	Systematic Assessment	EG00010 events10 affected214 at risk EG0014 events4 affected100 at risk
Viral upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG00010 events7 affected214 at risk EG0016 events5 affected100 at risk
Sinusitis	Infections and infestations	Systematic Assessment	EG0005 events5 affected214 at risk EG0014 events4 affected100 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0002 events2 affected214 at risk EG0012 events2 affected100 at risk
Acute sinusitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected214 at risk EG0012 events2 affected100 at risk
Gastroenteritis	Infections and infestations	Systematic Assessment	EG0001 events1 affected214 at risk EG0012 events2 affected100 at risk
Blood pressure increased	Investigations	Systematic Assessment	EG0009 events7 affected214 at risk EG0013 events3 affected100 at risk
Prostatic specific antigen increased	Investigations	Systematic Assessment	EG0005 events5 affected214 at risk EG0015 events5 affected100 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0009 events6 affected214 at risk EG0017 events6 affected100 at risk
Back Pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0007 events6 affected214 at risk EG0011 events1 affected100 at risk
Neck pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 events2 affected214 at risk EG0012 events2 affected100 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0013 events3 affected100 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected214 at risk EG0015 events3 affected100 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0006 events6 affected214 at risk EG0012 events2 affected100 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0005 events5 affected214 at risk EG0010 events0 affected100 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0009 events8 affected214 at risk EG0014 events4 affected100 at risk
Hypertension	Vascular disorders	Systematic Assessment	EG00019 events17 affected214 at risk EG0012 events2 affected100 at risk
Flushing	Vascular disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0012 events2 affected100 at risk
Sleep Apnoea syndrome	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0012 events2 affected100 at risk
Respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected214 at risk EG0014 events2 affected100 at risk
Limb injury	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected214 at risk EG0012 events2 affected100 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected214 at risk EG0012 events2 affected100 at risk
Oedema peripheral	General disorders	Systematic Assessment	EG0006 events5 affected214 at risk EG0010 events0 affected100 at risk
Chills	General disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0012 events2 affected100 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0004 events4 affected214 at risk EG0013 events2 affected100 at risk
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0013 events3 affected100 at risk
Acne	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0012 events2 affected100 at risk
Erythema	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected214 at risk EG0012 events2 affected100 at risk
Anxiety	Psychiatric disorders	Systematic Assessment	EG0006 events5 affected214 at risk EG0010 events0 affected100 at risk
Erectile dysfunction	Reproductive system and breast disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0012 events2 affected100 at risk
Peyronie's disease	Reproductive system and breast disorders	Systematic Assessment	EG0000 events0 affected214 at risk EG0012 events2 affected100 at risk
Pollakiuria	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected214 at risk EG0012 events2 affected100 at risk
Lower urinary tract symptoms	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected214 at risk EG0012 events2 affected100 at risk
Hypothyroidism	Endocrine disorders	Systematic Assessment	EG0000 events0 affected214 at risk EG0012 events2 affected100 at risk

ID	Term
D007006	Hypogonadism
D006058	Gonadal Disorders
D004700	Endocrine System Diseases

ID	Term
D000737	Androstenols
D000736	Androstenes
D000731	Androstanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D045165	Testosterone Congeners
D012739	Gonadal Steroid Hormones
D042341	Gonadal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists

ID	Title	Description
BG000	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 (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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)
BG001	Andro-Gel™ Treated	100 patients treated with AndroGel, according to label, using sampling on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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. SOV2012-F1: oral preparation of testosterone undecanoate (TU)	1	214	9	214	53	214
EG001	Andro-Gel Treated	100 patients treated with AndroGel, according to label, using samples on Days 14 and 42 with dose adjustment on Days 28 and 56. AndroGel: topical testosterone gel, 1.62%	0	100	1	100	25	100