Ambulatory Blood Pressure Monitoring (ABPM) Extension Stu... | NCT04467697

Name	Class
Syneos Health	OTHER

Label	Type	Description	Intervention Names
SOV2012-F1-treated	Experimental	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning and 400 mg in the evening) or titrated down to a minimum of 100 mg SOV2012-F1 per day (100 mg in the morning) based on plasma T after 14 and 42 days of treatment, intermediate dose levels include total daily doses of 600 mg, 400 mg and 200 mg.	Drug: SOV2012-F1

Name	Type	Description	Arm Group Labels	Other Names
SOV2012-F1	Drug	Oral preparation of testosterone undecanoate (TU). Strengths of 100 mg TU, 150 mg TU and 200 mg TU	SOV2012-F1-treated

Measure	Description	Time Frame
Change From Baseline in 24-hour Average Ambulatory Systolic Blood Pressure After 120 Days Treatment	Change from baseline in 24-hour Ambulatory Systolic Blood Pressure (sBP) after approximately 120 days treatment (Mixed Model Repeated Measures analysis).	120 days
Plasma and Serum Testosterone Efficacy of Oral SOV2012-F1 With up and Down Titration	Percentage of SOV2012-F1-treated subjects with a plasma NaF/EDTA plasma testosterone (T) Cavg within the normal range after 90 days of treatment using up- and down-titration as appropriate. Measured by Plasma T concentration using a starting daily dose of 400 mg SOV2012-F1.	90 days

Measure	Description	Time Frame
Change From Baseline in 24-hour Average Ambulatory Systolic Blood Pressure After 180 Days Treatment.	Ambulatory Blood Pressure Monitoring (ABPM) of the change from baseline in 24-hour average systolic blood pressure (sBP) after 120 and 180 (+/-) 3 days of treatment (Mixed Model Repeated Measures analysis).	120 and 180 days

Measure	Description	Time Frame
AEs, SAEs and AEs Leading to MRS-TU-2019EXT Study Withdrawal of SOV2012-F1 Treated Subjects.	Number of subjects of adverse events (AEs), serious adverse events (SAEs), and AEs leading to study withdrawal in SOV2012-F1-treated subjects	180 days
Observed and Change From Baseline in Systolic Blood Pressure Using In-clinic Measurement.

Eligibility Module

Eligibility Criteria

For all subjects participating in MRS-TU-2019EXT, whether rolling over from MRS-TU-2019 (after washout) or newly enrolling, the following MRS-TU-2019EXT Inclusion/Exclusion Criteria apply:

Inclusion Criteria:

1. Completion of MRS-TU-2019 Day 365/ End of Treatment

Exclusion Criteria:

Upper arm circumference > 45 cm.
Long distance driving or planned driving trip (> 60 mins duration where the subject is doing the driving) during period of wearing ABPM cuff.
Expected / known forthcoming change to antihypertensive medication(s) during the MRS-TU-2019 EXT extension study.
Cardiac arrhythmias that, in the opinion of the investigator, interfere with the ability of the ABPM recorder to obtain reliable measurements.
Use of T implantable pellets since completion of Day 365/EOT visit in MRS-TU- 2019.

For newly enrolling subjects into MRS-TU-2019EXT (naïve to MRS-TU-2019), the applicable Inclusion/Exclusion criteria from the MRS-TU-2019 study, also must be met :

MRS-TU-2019 Key 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
  - *for MRS-TU-2019EXT ABPM Extension Study, the in-clinic, average BP must be < 140/90 for inclusion into the MRS-TU-2019EXT study.
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.

MRS-TU-2019 Key Exclusion Criteria:

Serum PSA > 2.5 ng/ml and/or abnormal prostate gland on palpation, e.g., 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.

*For ABPM Extension Study Only: Newly Enrolled Subjects to MRS-TU-2019EXT ABPM Extension Study, patients must not have received prior testosterone replacement therapy within 8 weeks of the start of the study, with the exception of T implantable pellets which are excluded for 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 (e.g., 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 (e.g., 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, small bowel resection, or any surgical procedure or medications (e.g., GLP-1 agonists and motility agents such as domperidone, metoclopramide, etc.) 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, i.e., 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/1.73 m2 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 or 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.

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

Facility	Status	City	State	ZIP	Country	Contacts
Alabama Clinical Therapeutics, LLC		Birmingham	Alabama	35235	United States
Coastal Clinic Research Inc

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-2019 protocol, ClinicalTrials.gov ID: NCT03198728	View source

ID	Title	Description
FG000	SOV2012-F1-treated	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. Doses were up-titrated at Days 28 and 56 if the measured T-concentration in a NaF/EDTA plasma sample was below 400 ng/dL; down-titrated if the T-concentration was above 900 ng/dL, and no change if between those thresholds. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

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	Jun 7, 2023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in 24-hour Average Ambulatory Systolic Blood Pressure After 120 Days Treatment

Change from baseline in 24-hour Ambulatory Systolic Blood Pressure (sBP) after approximately 120 days treatment (Mixed Model Repeated Measures analysis).

Extension Treated Set

Posted

Least Squares Mean

95% Confidence Interval

mmHg

120 days

ID	Title	Description
OG000	SOV2012-F1-treated	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Units	Counts
Participants	OG000139

Title

Denominators

Categories

Baseline

Title	Measurements
	OG000128.9(126.8 to 131.0)

Observed Visit 14E - Day 120E

Title	Measurements
	OG000130.6(128.5 to 132.7)

Change from baseline (Visit 14E - Day 120E)

Primary

Plasma and Serum Testosterone Efficacy of Oral SOV2012-F1 With up and Down Titration

Percentage of SOV2012-F1-treated subjects with a plasma NaF/EDTA plasma testosterone (T) Cavg within the normal range after 90 days of treatment using up- and down-titration as appropriate. Measured by Plasma T concentration using a starting daily dose of 400 mg SOV2012-F1.

Modified Extension Treated Set

Posted

Number

95% Confidence Interval

percentage of participants

90 days

ID	Title	Description
OG000	NaF/EDTA PLASMA	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg with morning meal and 400 mg with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 me twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths. Patients (n=16) from a single clinical site were excluded from PK-based outcomes due to sample handling errors.
OG001	SERUM	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg with morning meal and 400 mg with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 me twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths. Patients (n=16) from a single clinical site were excluded from PK-based outcomes due to sample handling errors. Patients were enrolled in the serum sub study.

Secondary

Change From Baseline in 24-hour Average Ambulatory Systolic Blood Pressure After 180 Days Treatment.

Ambulatory Blood Pressure Monitoring (ABPM) of the change from baseline in 24-hour average systolic blood pressure (sBP) after 120 and 180 (+/-) 3 days of treatment (Mixed Model Repeated Measures analysis).

Extension Treated Set

Posted

Least Squares Mean

95% Confidence Interval

mmHg

120 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Units	Counts
Participants

Secondary

Change From Baseline in 24-hour Average Ambulatory Diastolic Blood Pressure (dBP) After 120 Days and 180 Days of SOV2012-F1 Treatment.

Ambulatory Blood Pressure Monitoring (ABPM) of the change from baseline in 24-hour average diastolic blood pressure (dBP) after 120 Days (+/-) and 180 (+/-) 3 days of treatment (Mixed Model Repeated Measures analysis).

Extension Treated Set

Posted

Least Squares Mean

95% Confidence Interval

mmHg

120 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Units	Counts
Participants

Secondary

Change From Baseline in 24-hour Average Ambulatory Heart Rate After 120 Days and 180 Days of Treatment.

Ambulatory Blood Pressure Monitoring (ABPM) at 120 Days (+/-3) and after 180 Days (+/- 3) of SOV2012-F1 Treatment (Mixed Model Repeated Measures analysis.

Extension Treated Set

Posted

Least Squares Mean

95% Confidence Interval

bpm

120 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Units	Counts
Participants	OG000

Secondary

Observed and Change From Baseline in Ambulatory Half Hourly Systolic Blood Pressure, After 120 Days and After 180 Days of SOV2012-F1 Treatment.

Observed and change from baseline in Ambulatory half hourly systolic blood pressure as measured by ABPM after 120 Days (+/-3) and after 180 Days (+/-3) of SOV2012-F1 treatment.

Extension Treated Set

Posted

Mean

Standard Deviation

mmHg

120 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated - Systolic Blood Pressure (sBP), Baseline	Baseline Ambulatory Blood Pressure Monitoring, sBP.
OG001	SOV2012-F1-treated - Systolic Blood Pressure (sBP), Visit 14E - Day 120E	Observed Ambulatory Blood Pressure Monitoring sBP after 120 days of treatment with SOV2012-F1.
OG002	SOV2012-F1-treated - Systolic Blood Pressure (sBP), Change From Baseline, Visit 14E - Day 120E	Change from baseline for Ambulatory Blood Pressure Monitoring sBP after 120 days of treatment with SOV2012-F1.
OG003	SOV2012-F1-treated - Systolic Blood Pressure (sBP), Visit 16E - Day 180E

Secondary

Observed and Change From Baseline in Ambulatory Half Hourly Diastolic Blood Pressure, After 120 Days and After 180 Days of SOV2012-F1 Treatment.

Observed and change from baseline in Ambulatory half hourly diastolic blood pressure as measured by ABPM after 120 Days (+/-3) and after 180 Days (+/-3) of SOV2012-F1 treatment.

Extension Treated Set

Posted

Mean

Standard Deviation

mmHg

120 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated - Diastolic Blood Pressure (dBP), Baseline	Baseline Ambulatory Blood Pressure Monitoring, dBP.
OG001	SOV2012-F1-treated - Diastolic Blood Pressure (dBP), Visit 14E - Day 120E	Observed Ambulatory Blood Pressure Monitoring dBP after 120 days of treatment with SOV2012-F1.
OG002	SOV2012-F1-treated - Diastolic Blood Pressure (dBP), Change From Baseline, Visit 14E - Day 120E	Change from baseline for Ambulatory Blood Pressure Monitoring dBP after 120 days of treatment with SOV2012-F1.
OG003	SOV2012-F1-treated - Diastolic Blood Pressure (dBP), Visit 16E - Day 180E

Secondary

Observed and Change From Baseline in Ambulatory Half Hourly Heart Rate Measurement, After 120 Days and After 180 Days (±3) of SOV2012-F1 Treatment.

Observed and change from baseline in Ambulatory half hourly heart rate as measured by ABPM after 120 Days (+/-3) and after 180 Days (+/-3) of SOV2012-F1 treatment.

Extension Treated Set

Posted

Mean

Standard Deviation

bpm

120 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated - Heart Rate (Bpm), Baseline	Baseline Ambulatory Blood Pressure Monitoring (ABPM) heart rate.
OG001	SOV2012-F1-treated - Heart Rate (Bpm), Visit 14E - Day 120E	Observed Ambulatory Blood Pressure Monitoring heart rate after 120 days of treatment with SOV2012-F1.
OG002	SOV2012-F1-treated - Heart Rate (Bpm), Change From Baseline, Visit 14E - Day 120E	Change from Baseline for Ambulatory Blood Pressure Monitoring heart rate after 120 days of treatment with SOV2012-F1.
OG003	SOV2012-F1-treated - Heart Rate (Bpm), Visit 16E - Day 180E

Secondary

Percentage of SOV2012-F1-Treated Subjects With Maximum Plasma Testosterone Concentration After 90 Days of Treatment: < 1.5X Upper Limit of Normal (ULN); 1.8 to ≤ 2.5X ULN; > 2.5X ULN

Percentage of SOV2012-F1 treated subjects with maximum NaF/EDTA plasma T levels falling into three concentration groups after 90 days of treatment with SOV2012-F1.

Modified Extension Treatment Set

Posted

Count of Participants

Participants

90 days

ID	Title	Description
OG000	NaF/EDTA PLASMA	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg with morning meal and 400 mg with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 me twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths. Patients (n=16) from a single clinical site were excluded from PK-based outcomes due to sample handling errors.

Units	Counts
Participants

Secondary

Percentage of SOV2012-F1-Treated Subjects With Maximum Serum Testosterone Concentration After 90 Days of Treatment: < 1.5X Upper Limit of Normal (ULN); 1.8 to ≤ 2.5X ULN; > 2.5X ULN

Percentage of SOV2012-F1 treated subjects with maximum serum levels falling into three concentration groups after 90 days of treatment with SOV2012-F1.

Modified Extension Treatment Set

Posted

Count of Participants

Participants

90 days

ID	Title	Description
OG000	SERUM	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg with morning meal and 400 mg with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 me twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths. Patients (n=16) from a single clinical site were excluded from PK-based outcomes due to sample handling errors. Patients were participants in the Serum sub study.

Units	Counts
Participants

Other Pre-specified

AEs, SAEs and AEs Leading to MRS-TU-2019EXT Study Withdrawal of SOV2012-F1 Treated Subjects.

Number of subjects of adverse events (AEs), serious adverse events (SAEs), and AEs leading to study withdrawal in SOV2012-F1-treated subjects

Extension Treated Set

Posted

Count of Participants

Participants

180 days

ID	Title	Description
OG000	SOV2012-F1-treated	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Units	Counts
Participants	OG000

Other Pre-specified

Observed and Change From Baseline in Systolic Blood Pressure Using In-clinic Measurement.

Measured by in-clinic BP measurement of sBP, mmHg, observed and change from baseline at baseline, 90, 120 and 180 days after treatment with SOV2012-F1.

Extension Treated Set

Posted

Mean

Standard Deviation

mmHg

Baseline, 90, 119 and 179 days

ID	Title	Description
OG000	SOV2012-F1-treated, Observed	Observed systolic BP measured in-clinic at baseline, and 90, 120 and 180 days of treatment with SOV2012-F1
OG001	SOV2012-F1-treated, Change From Baseline	Change in baseline for systolic BP measured in-clinic after 90, 120 and 180 days of treatment with SOV2012-F1

Units	Counts
Participants	OG000

Other Pre-specified

Observed and Change From Baseline in Heartrate (HR) Obtained In-clinic During the Treatment Period.

Measured by in-clinic HR measurement, beats per minute during the treatment period, at baseline, and after 90, 120 and 180 days of treatment with SOV2012-F1.

Extension Treated Set

Posted

Mean

Standard Deviation

beats/minute

Baseline, 90, 119 and 179 days

ID	Title	Description
OG000	SOV2012-F1-treated, Observed	Observed heartrate (HR) measured in-clinic at baseline, and 90, 120 and 180 days of treatment with SOV2012-F1.
OG001	SOV2012-F1-treated, Change From Baseline	Change from baseline for heartrate (HR) measured in-clinic at 90, 120 and 180 days of treatment with SOV2012-F1.

Units	Counts
Participants	OG000

Other Pre-specified

Observed and Change From Baseline in Hematology Parameters in Liver Function Tests of ALT, AST and Alkaline Phosphatase

Alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase in SOV2012-F1 treated subjects were assessed during the treatment period, measurement units of Units per Liter (U/L)

Extension Treated Set

Posted

Mean

Standard Deviation

U/L

90 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated, Observed	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.
OG001	SOV2012-F1-treated, Change From Baseline	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Other Pre-specified

Observed and Change From Baseline in Hematology Parameters in Liver Function Tests

Total bilirubin in SOV2012-F1 treated subjects were assessed during the treatment period, measurement units of mg/dL

Extension Treated Set

Posted

Mean

Standard Deviation

mg/dL

90 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated, Observed	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.
OG001	SOV2012-F1-treated, Change From Baseline	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Other Pre-specified

Observed and Change From Baseline in Hematology Parameters (Hemoglobin) in SOV2012-F1 Treated Subjects During the Treatment Period.

Hemoglobin in SOV2012-F1 treated subjects were assessed during the treatment period, measurement units of g/dL.

Extension Treated Set

Posted

Mean

Standard Deviation

g/dL

90 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated, Observed	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.
OG001	SOV2012-F1-treated, Change From Baseline	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Other Pre-specified

Observed and Change From Baseline in Hormone Levels.

Luteinizing hormone [LH] and follicle-stimulating hormone [FSH] in SOV2012-F1 treated subjects during the treatment period, measurement units of mIU/mL.

Extension Treated Set

Posted

Mean

Standard Deviation

mIU/mL

90 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated, Observed	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.
OG001	SOV2012-F1-treated, Change From Baseline	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Other Pre-specified

Observed and Change From Baseline in Hormone Levels for SHBG.

Sex hormone-binding globulin [SHBG] in SOV2012-F1 treated subjects were assessed during the treatment period, measurement units of nmol/L.

Extension Treated Set

Posted

Mean

Standard Deviation

nmol/L

90 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated, Observed	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.
OG001	SOV2012-F1-treated, Change From Baseline	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Other Pre-specified

Observed and Change From Baseline in Thyrotropin

Thyroid stimulating hormone [TSH] in SOV2012-F1 treated subjects were assessed during the treatment period, measurement units of mU/L.

Extension Treated Set

Posted

Mean

Standard Deviation

mU/L

90 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated, Observed	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.
OG001	SOV2012-F1-treated, Change From Baseline	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Other Pre-specified

Observed and Change From Baseline in Lipid Profiles in SOV2012-F1 Treated Subjects During the Treatment Period.

Lipid profiles (high and low-density lipoproteins, total cholesterol, triglycerides) in SOV2012-F1 treated subjects were assessed during the treatment period, measurement units of mg/dL.

Extension Treated Set

Posted

Mean

Standard Deviation

mg/dL

90 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated, Observed	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.
OG001	SOV2012-F1-treated, Change From Baseline	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Other Pre-specified

Observed and Change From Baseline in Serum Prostate-specific Antigen (PSA) in SOV2012-F1 Treated Subjects During the Treatment Period.

Serum prostate-specific antigen (PSA) in SOV2012-F1 treated subjects were assessed during the treatment period, measurement units of ng/mL.

Extension Treated Set

Posted

Mean

Standard Deviation

ng/mL

90 and 180 days

ID	Title	Description
OG000	SOV2012-F1-treated, Observed	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.
OG001	SOV2012-F1-treated, Change From Baseline	Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 800 mg SOV2012-F1 per day (400 mg in the morning with morning meal and 400 mg in the evening with evening meal) or down to a minimum of 100 mg SOV2012-F1 per day (100 mg with morning meal) based on plasma T after 14 and 42 days of treatment. Patients could be titrated to final daily dose levels of 100 mg, 200 mg (100 mg twice daily), 400 mg (200 mg twice daily), 600 mg (300 mg twice daily) or 800 mg (400 mg twice daily). All doses taken with meals. SOV2012-F1: oral preparation of testosterone undecanoate (TU) in 100 mg, 150 mg and 200 mg strengths.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA 20.0	Systematic Assessment	Event judged not treatment related by investigator.	EG0001 events1 affected155 at risk
Diverticular perforation	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	Event judged not treatment related by investigator.	EG0001 events1 affected155 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Hypertension	Vascular disorders	MedDRA 20.0	Systematic Assessment		EG0004 events4 affected155 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0008 events8 affected155 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0005 events5 affected155 at risk
Influenza	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0004 events4 affected155 at risk
Bronchitis	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0003 events3 affected155 at risk
Hemoglobin increased	Investigations	MedDRA 20.0	Systematic Assessment	Event judged as treatment related by investigator.	EG0003 events3 affected155 at risk
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment		EG0003 events3 affected155 at risk

ID	Term
D007006	Hypogonadism
D006058	Gonadal Disorders
D004700	Endocrine System Diseases