NCT04467697 · CITED IN SOURCE DOCUMENTS

Ambulatory Blood Pressure Monitoring (ABPM) Extension Study of Oral Testosterone Undecanoate in Hypogonadal Men

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2024-06-28

The purpose of this six-month treatment study is * to assess feasibility of a lower starting dose of SOV2012-F1 (daily dose of 400 mg \[200 mg with breakfast meal and 200mg with dinner meal\]) to titrate individual doses to further enhance efficacy and safety. * To examine the blood pressure (BP) effects of Marius's oral testosterone undecanoate formulation, SOV2012-F1, using 24-hour ambulatory blood pressure monitoring (ABPM).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Observed and Change From Baseline in Hormone Levels.

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outcome · POSTED

Observed and Change From Baseline in Hormone Levels for SHBG.

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outcome · POSTED

Observed and Change From Baseline in Thyrotropin

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outcome · POSTED

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

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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: 1. Upper arm circumference \> 45 cm. 2. Long distance driving or planned driving trip (\> 60 mins duration where the subject is doing the driving) during period of wearing ABPM cuff. 3. Expected / known forthcoming change to antihypertensive medication(s) during the MRS-TU-2019 EXT extension study. 4. Cardiac arrhythmias that, in the opinion of the investigator, interfere with the ability of the ABPM recorder to obtain reliable measurements. 5. 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: 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 * \*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. 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. MRS-TU-2019 Key Exclusion Criteria: 1. Serum PSA \> 2.5 ng/ml and/or abnormal prostate gland on palpation, e.g., 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. \*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. 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 (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. 4. 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. 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, 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. 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, i.e., 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/1.73 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. 16. Severe or 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.
gender Based: true
healthy Volunteers: false
maximum Age: 65 Years
minimum Age: 18 Years
sex: MALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: SOV2012-F1
label
SOV2012-F1-treated
type
EXPERIMENTAL

interventions

arm Group Labels
SOV2012-F1-treated
description
Oral preparation of testosterone undecanoate (TU). Strengths of 100 mg TU, 150 mg TU and 200 mg TU
name
SOV2012-F1
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 155
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
Number of subjects of adverse events (AEs), serious adverse events (SAEs), and AEs leading to study withdrawal in SOV2012-F1-treated subjects
measure
AEs, SAEs and AEs Leading to MRS-TU-2019EXT Study Withdrawal of SOV2012-F1 Treated Subjects.
time Frame
180 days
description
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.
measure
Observed and Change From Baseline in Systolic Blood Pressure Using In-clinic Measurement.
time Frame
Baseline, 90, 119 and 179 days
description
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.
measure
Observed and Change From Baseline in Heartrate (HR) Obtained In-clinic During the Treatment Period.
time Frame
Baseline, 90, 119 and 179 days
description
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)
measure
Observed and Change From Baseline in Hematology Parameters in Liver Function Tests of ALT, AST and Alkaline Phosphatase
time Frame
90 and 180 days
description
Total bilirubin in SOV2012-F1 treated subjects were assessed during the treatment period, measurement units of mg/dL
measure
Observed and Change From Baseline in Hematology Parameters in Liver Function Tests
time Frame
90 and 180 days
description
Hemoglobin in SOV2012-F1 treated subjects were assessed during the treatment period, measurement units of g/dL.
measure
Observed and Change From Baseline in Hematology Parameters (Hemoglobin) in SOV2012-F1 Treated Subjects During the Treatment Period.
time Frame
90 and 180 days
description
Luteinizing hormone \[LH\] and follicle-stimulating hormone \[FSH\] in SOV2012-F1 treated subjects during the treatment period, measurement units of mIU/mL.
measure
Observed and Change From Baseline in Hormone Levels.
time Frame
90 and 180 days
description
Sex hormone-binding globulin \[SHBG\] in SOV2012-F1 treated subjects were assessed during the treatment period, measurement units of nmol/L.
measure
Observed and Change From Baseline in Hormone Levels for SHBG.
time Frame
90 and 180 days
description
Thyroid stimulating hormone \[TSH\] in SOV2012-F1 treated subjects were assessed during the treatment period, measurement units of mU/L.
measure
Observed and Change From Baseline in Thyrotropin
time Frame
90 and 180 days
description
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.
measure
Observed and Change From Baseline in Lipid Profiles in SOV2012-F1 Treated Subjects During the Treatment Period.
time Frame
90 and 180 days
description
Serum prostate-specific antigen (PSA) in SOV2012-F1 treated subjects were assessed during the treatment period, measurement units of ng/mL.
measure
Observed and Change From Baseline in Serum Prostate-specific Antigen (PSA) in SOV2012-F1 Treated Subjects During the Treatment Period.
time Frame
90 and 180 days

primary Outcomes

description
Change from baseline in 24-hour Ambulatory Systolic Blood Pressure (sBP) after approximately 120 days treatment (Mixed Model Repeated Measures analysis).
measure
Change From Baseline in 24-hour Average Ambulatory Systolic Blood Pressure After 120 Days Treatment
time Frame
120 days
description
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.
measure
Plasma and Serum Testosterone Efficacy of Oral SOV2012-F1 With up and Down Titration
time Frame
90 days

secondary Outcomes

description
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).
measure
Change From Baseline in 24-hour Average Ambulatory Systolic Blood Pressure After 180 Days Treatment.
time Frame
120 and 180 days
description
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).
measure
Change From Baseline in 24-hour Average Ambulatory Diastolic Blood Pressure (dBP) After 120 Days and 180 Days of SOV2012-F1 Treatment.
time Frame
120 and 180 days
description
Ambulatory Blood Pressure Monitoring (ABPM) at 120 Days (+/-3) and after 180 Days (+/- 3) of SOV2012-F1 Treatment (Mixed Model Repeated Measures analysis.
measure
Change From Baseline in 24-hour Average Ambulatory Heart Rate After 120 Days and 180 Days of Treatment.
time Frame
120 and 180 days
description
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.
measure
Observed and Change From Baseline in Ambulatory Half Hourly Systolic Blood Pressure, After 120 Days and After 180 Days of SOV2012-F1 Treatment.
time Frame
120 and 180 days
description
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.
measure
Observed and Change From Baseline in Ambulatory Half Hourly Diastolic Blood Pressure, After 120 Days and After 180 Days of SOV2012-F1 Treatment.
time Frame
120 and 180 days
description
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.
measure
Observed and Change From Baseline in Ambulatory Half Hourly Heart Rate Measurement, After 120 Days and After 180 Days (±3) of SOV2012-F1 Treatment.
time Frame
120 and 180 days
description
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.
measure
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
time Frame
90 days
description
Percentage of SOV2012-F1 treated subjects with maximum serum levels falling into three concentration groups after 90 days of treatment with SOV2012-F1.
measure
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
time Frame
90 days

Full study description

brief Summary: The purpose of this six-month treatment study is * to assess feasibility of a lower starting dose of SOV2012-F1 (daily dose of 400 mg \[200 mg with breakfast meal and 200mg with dinner meal\]) to titrate individual doses to further enhance efficacy and safety. * To examine the blood pressure (BP) effects of Marius's oral testosterone undecanoate formulation, SOV2012-F1, using 24-hour ambulatory blood pressure monitoring (ABPM).
detailed Description: This is the six-month treatment extension of Study MRS-TU-2019, which like Study MRS-TU-2019 (NCT03198728), is an open-label study. The MRS-TU-2019 ABPM Extension Study (MRS-TU-2019EXT; NCT04467697), will extend the participation for up to 170 MRS-TU-2019 subjects and to new subjects, for a target of 135 evaluable subjects reaching the 4-month ABPM assessment. All subjects were washed out from previous testosterone therapy if they were not naïve. The study used ABPM monitoring to assess baseline and change from baseline after 120 and 180 days of treatment. The percentage of participants within the normal range for testosterone was assessed after two titration cycles and a total of 90 days of treatment.

Source references

references

citation
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.
pmid
38606384
type
DERIVED