Hypogonadism, Male
Conditions
Brief summary
This will be a randomized, multicenter, open-label, active-controlled, efficacy, and safety study in adult hypogonadal men. The study duration is 12 months (365 days), including a 90-day, open-label efficacy period and a 9-month (275-day) safety evaluation period.
Detailed description
MRS-TU-2019 was a 12-month study designed to determine the efficacy of oral SOV2012-F1 as measured by the percentage of male hypogonadal subjects with average total testosterone (T Cavg) in plasma within the normal range after 90 days of treatment. This study included an AndroGel™ arm as a safety comparator; after the 90-day efficacy period, dosing continued for 9 additional months in both arms to gather safety data. This study also examined the percentage of SOV2012-F1-treated subjects with maximum total testosterone (Cmax) in plasma values after 90 days of treatment: a. ≤1.5 X upper limit of normal (ULN); b. 1.8 X ULN to 2.5 X ULN' and c. \>2.5 X ULN. The study also included an adrenal cortical function substudy conducted in 30 SOV2012-F1 subjects and 15 AndroGel subjects. Four patient-reported outcome measures were also used during the study: IPSS, PDQ, SF-36 and IIEF.
Interventions
DRUGSOV2012-F1
oral preparation of testosterone undecanoate (TU)
DRUGAndroGel
topical testosterone gel 1.62%
Sponsors
Syneos Health
Marius Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Open label
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male aged 18 to 65 years, inclusive, at the time of providing informed consent to participate in the study. 2. Hypogonadism defined as having 2 consecutive serum total T levels≤ 281 ng/dL based on a blood sample, drawn at least 3 days apart, between 7 a.m. and 10 a.m. 3. At least 1 clinical feature consistent with male hypogonadism. If a subject is receiving commercial TRT prior to Screening Visit 1, he must have a history of at least 1 clinical feature consistent with male hypogonadism. 4. Must be naïve to androgen replacement therapy or washed out adequately of prior androgen replacement therapies; willing to cease current T treatment; or currently not taking any T treatment. Subjects must remain off all forms of T, except for dispensed study drug, throughout the entire study. 5. No unstable ongoing concomitant medical conditions. Treated and well-controlled conditions such as type 2 diabetes, hypertension, or dyslipidemia are acceptable with stable medication in place for at least 3 months prior to study entry: 1. Hemoglobin A1c ≤ 8.0% 2. BP \< 150/90 mm Hg 3. Low-density lipoprotein cholesterol \< 190 mg/dL. 6. Subjects with an endocrine disorder requiring treatment other than hypogonadism must be on a stable dose of replacement medication for at least 3 months prior to study entry. 7. Adequate venous access to allow collection of a number of blood samples via a venous cannula. 8. Written informed consent to participate in the study and ability to comply with all study requirements.
Exclusion criteria
1. Serum PSA \> 2.5 ng/ml and/or abnormal prostate gland on palpation, eg, palpable nodes, at Screening Visit 2. 2. Received oral, topical, intranasal, or buccal T therapy within the previous 2 weeks, intramuscular T injection of short-acting duration within the previous 4 weeks, intramuscular T injection of long-acting duration within the previous 20 weeks, or T implantable pellets within the previous 6 months. 3. Use of any drug that could interfere with measurement or assessment of serum androgen levels, including 5 alpha-reductase inhibitors, anabolic steroids, and drugs with antiandrogenic properties (eg, spironolactone, cimetidine, flutamide, bicalutamide, and ketoconazole). These drugs must be stopped for at least 1 month prior to study entry (6 months in the case of dutasteride). Patients taking potent, long-acting opiate therapy on a daily basis are not eligible for the study. Conversely, ad hoc use of potent, short-acting opiates for a period of less than 7 days may be permitted after discussion with the Marius Pharmaceuticals medical monitor. 4. Use of over-the-counter products, including natural health products (eg, food supplements and herbal supplements such as saw palmetto or phytoestrogens) that may affect total T levels, within 7 days prior to study entry. 5. History of drug or alcohol abuse within the past 2 years that in the opinion of the investigator could interfere with study participation and/or influence study efficacy and safety endpoints assessments. 6. Unstable or chronic disease that could interfere with participation in the study or patient safety, including psychiatric disorders. 7. Myocardial infarction, coronary artery surgery, heart failure, stroke, unstable angina, or other unstable cardiovascular disease within the past 6 months. 8. Abnormal ECG considered clinically significant by investigator at Screening. 9. Diagnosis of any cancer within the previous 5 years other than basal or squamous cell skin cancer with clear margins. 10. Any surgical or medical condition that might alter administration of the study drug or comparator, including history of gastric surgery, cholecystectomy, vagotomy, bowel resection, or any surgical procedure that might interfere with gastrointestinal motility, pH, or absorption of TU. 11. Duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to screening. 12. Chronic skin conditions on the chest or upper arms that would prevent administration of AndroGel in a manner designed to ensure reliable and consistent absorption thereof. 13. Human immunodeficiency virus (HIV) infection. 14. Chronic hepatitis B virus and/or hepatitis C virus (HCV) infection (as determined by positive testing for hepatitis B virus surface antigen or HCV antibody with confirmatory testing, ie, detectable serum HCV ribonucleic acid \[RNA\]). 15. Clinically significant abnormal laboratory values at screening including but not limited to: 1. Elevated liver enzymes (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\] \> 2x upper limit of normal) 2. Estimated glomerular filtration rate \< 60 ml/min/1.73m2 as calculated by the Modification of Diet in Renal Disease formula 3. Hemoglobin \< 11.0 g/dL or \> 16.0 g/dL. For a subject previously on testosterone replacement therapy with less than 30 days washout prior to screening Visit 2, hemoglobin \< 11.0 g/dL or \> 17.0 g/dL. 16. Severe and untreated obstructive sleep apnea syndrome. 17. Severe lower urinary tract symptoms (American Urological Association/ IPSS ≥ 19). 18. History of any clinically significant illness, infection, or surgical procedure within 1 month prior to study entry. 19. Past, current, or suspected prostate or breast cancer. 20. History of long QT syndrome or unexplained sudden death in a first-degree relative (parent, sibling, or child). 21. Concurrent treatment with medications that may impact the absorption, distribution, metabolism, or excretion of TU or place the subject at risk for treatment with T. 22. Subject has a partner who is currently pregnant or planning pregnancy during the course of the study. 23. Treatment with any other investigational drug within 30 days of study entry or \> 5 half-lives (whichever is longer) and at any time during the study. 24. History of noncompliance to medical regimens or potential unreliability in the opinion of the investigator. 25. Unwilling or unable to comply to the dietary requirements for this study. 26. History of polycythemia, either idiopathic or associated with TRT. 27. Donated blood (≥ 500 mL) within the 12-week period prior to study entry. 28. History of an abnormal bleeding tendency or thrombophlebitis within the previous 2 years that is not linked to venipuncture or intravenous cannulation. 29. Onset of gynecomastia within the previous 6 months. 30. For adrenocorticotropic hormone (ACTH) stimulation substudy only: Primary or secondary adrenal insufficiency. 31. For Bioanalytical Sample Stability Substudy only: subjects with a hemoglobin less than 13 g/dL at most recent assessment\* \[should be excluded\].
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Male Hypogonadal Subjects With Average NaF/EDTA Plasma Total Testosterone (T Cavg) Within the Normal Range Using Oral SOV2012-F1. | 90 days | Efficacy assessment includes T Cavg calculated from NaF/EDTA plasma testosterone. The T Cavg is calculated as the 24-hour area under the curve (AUC), divided by 24, at Day 90, based on a fifteen blood samples (PK samples) taken over the 24-hours. The T concentration in each sample is measured using a validated LC-MS/MS method. The use of NaF/EDTA plasma tubes chilled after sample collection provides the most accurate values, as the prodrug TU may degrade post-sample collection, artificially inflating testosterone values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentages of Participants in Each Category for Maximum Plasma Concentration | 90 days | 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
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the SF-36 | Baseline (Day 1, pre-treatment) and change from baseline at the End of Treatment (EOT) | Patient reported outcomes assessed by the Short-Form Survey (SF-36). This scale assesses 8 health concepts: 1. limitations in physical activities because of health problems 2. limitations in social activities because of physical or emotional problems 3. limitations in usual role activities because of physical health problems 4. bodily pain 5. general mental health (psychological distress and well-being) 6. limitations in usual role activities because of emotional problems 7. vitality (energy and fatigue) 8. 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. |
| Change From Baseline in the IIEF | Baseline (Day 1, pre-treatment) and change from baseline at the End of Treatment (EOT) | 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. |
| Change From Baseline in Fasting Serum Glucose (FSG) Concentration | Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment. | 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. |
| Change From Baseline in Fasting Insulin Concentration | Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment. | 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. |
| Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment. | 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. |
| Change From Baseline in Liver Function Tests | Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment. | Liver function tests (ALT, AST, total bilirubin, alkaline phosphatase). The liver function test results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The reported value is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value. A positive value for Change in Baseline represents an increase in the liver function test value |
| Change in Bilirubin | Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment. | Change in bilirubin from Baseline The bilirubin test results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The reported value is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value. A positive value for Change in Baseline represents an increase in the bilirubin value. |
| Change From Baseline in the IPSS | Baseline (pre-treatment) to 90 days and 365 days | 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. |
| Change From Baseline in Hormone Levels | Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment | 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. |
| Change in Hormone SHBG | Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment | Change in hormone Sex Hormone Binding Globulin (SHBG). The hormone level test results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value at Day 90 or Day 365. A positive value for Change in Baseline represents an increase in the hormone level. |
| Change in TSH (Thyrotropin) | Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment | Change from Baseline in Thyroid stimulating Hormone (TSH). The TSH test results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment. End of treatment occurred either at time of early withdrawal from the study or at Day 365. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value at Day 90 or Day 365. A positive value for Change in Baseline represents an increase in the TSH level. |
| Change From Baseline in Lipid Profiles | Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270, Day 365 and the End of Treatment | 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. |
| Change From Baseline in PSA | Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270, Day 365 and the End of Treatment | Serum prostate-specific antigen (PSA). The PSA results are reported at Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270, Day 365 and the End of Treatment. End of Treatment occurred either at time of early withdrawal from the study or at Day 365. The reported value is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value. A positive value for Change in Baseline represents an increase in the PSA value. |
| Effect of SOV2012-F1 on Adrenal Cortical Function as Assessed by Measuring the Cortisol Response to Synthetic ACTH at Baseline in Subjects | 52 weeks | To determine the effect of SOV2012-F1 on adrenal cortical function as assessed by measuring the cortisol response to synthetic ACTH at baseline and after 52 weeks of treatment in a subset of SOV2012-F1 subjects. . 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). |
| Change From Baseline in Hematology Parameters | Baseline (Day 1, pre-treatment) and the change from baseline at the End of Treatment | 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%. |
| Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Baseline (pre-treatment) to 90 days and 365 days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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) | 214 |
| 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% | 100 |
| Total | 314 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 5 |
| Overall Study | Lost to Follow-up | 21 | 7 |
| Overall Study | Physician Decision | 7 | 2 |
| Overall Study | Withdrawal by Subject | 14 | 10 |
Baseline characteristics
| Characteristic | SOV2012-F1-Treated | Andro-Gel™ Treated | Total |
|---|---|---|---|
| Age, Continuous | 49.2 years STANDARD_DEVIATION 9.15 | 50.7 years STANDARD_DEVIATION 9.3 | 49.7 years STANDARD_DEVIATION 9.21 |
| Assigned breakfast diet High-fat Breakfast | 130 Participants | — | 130 Participants |
| Assigned breakfast diet Low-fat Breakfast | 27 Participants | — | 27 Participants |
| Assigned breakfast diet Missing | 3 Participants | — | 3 Participants |
| Assigned breakfast diet Normal-fat Breakfast | 54 Participants | — | 54 Participants |
| Body Mass Index (BMI) | 34.12 kg/m^2 STANDARD_DEVIATION 7.056 | 34.33 kg/m^2 STANDARD_DEVIATION 6.486 | 34.19 kg/m^2 STANDARD_DEVIATION 6.87 |
| Diabetic Status With Diabetes Mellitus | 31 Participants | 13 Participants | 44 Participants |
| Diabetic Status Without Diabetes Mellitus | 183 Participants | 87 Participants | 270 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 55 Participants | 27 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 159 Participants | 73 Participants | 232 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hypertensive Status Hypertensive | 127 Participants | 60 Participants | 187 Participants |
| Hypertensive Status Not Hypertensive | 87 Participants | 40 Participants | 127 Participants |
| Hypertensive Treatment Status With Antihypertensive Therapy at Visit 3 (Day 1) | 67 Participants | 43 Participants | 110 Participants |
| Hypertensive Treatment Status Without Antihypertensive Therapy at Visit 3 (Day 1) | 147 Participants | 57 Participants | 204 Participants |
| Hypogonadal Status Primary | 8 Participants | 3 Participants | 11 Participants |
| Hypogonadal Status Secondary | 206 Participants | 97 Participants | 303 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 34 Participants | 11 Participants | 45 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) White | 171 Participants | 86 Participants | 257 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 214 Participants | 100 Participants | 314 Participants |
| Weight at Baseline | 108.48 kg STANDARD_DEVIATION 22.827 | 108.97 kg STANDARD_DEVIATION 24.544 | 108.63 kg STANDARD_DEVIATION 23.349 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 214 | 0 / 100 |
| other Total, other adverse events | 53 / 214 | 25 / 100 |
| serious Total, serious adverse events | 9 / 214 | 1 / 100 |
Outcome results
Primary
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.
Time frame: 90 days
Population: Efficacy Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOV2012-F1 Treated | Percentage of Male Hypogonadal Subjects With Average NaF/EDTA Plasma Total Testosterone (T Cavg) Within the Normal Range Using Oral SOV2012-F1. | 166 Participants |
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.
Time frame: 90 days
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOV2012-F1 Treated | Percentages of Participants in Each Category for Maximum Plasma Concentration | T Cmax < 1200 ng/dL for SOV2012-F1; T Cmax < 1500 ng/dL for Andro-gel after 90 days | 76.9 percentage of actual number of subjects |
| SOV2012-F1 Treated | Percentages of Participants in Each Category for Maximum Plasma Concentration | T Cmax 1440 to 2000 ng/dL for SOV2012-F1; T Cmax 1800 to 2500 ng/dL for Andro-gel after 90 days | 7.5 percentage of actual number of subjects |
| SOV2012-F1 Treated | Percentages of Participants in Each Category for Maximum Plasma Concentration | T Cmax > 2000 ng/dL for SOV2012-F1; T Cmax > 2500 ng/dL for Andro-gel after 90days | 3.2 percentage of actual number of subjects |
| Andro-gel™ Treated | Percentages of Participants in Each Category for Maximum Plasma Concentration | T Cmax < 1200 ng/dL for SOV2012-F1; T Cmax < 1500 ng/dL for Andro-gel after 90 days | 92.2 percentage of actual number of subjects |
| Andro-gel™ Treated | Percentages of Participants in Each Category for Maximum Plasma Concentration | T Cmax 1440 to 2000 ng/dL for SOV2012-F1; T Cmax 1800 to 2500 ng/dL for Andro-gel after 90 days | 2.2 percentage of actual number of subjects |
| Andro-gel™ Treated | Percentages of Participants in Each Category for Maximum Plasma Concentration | T Cmax > 2000 ng/dL for SOV2012-F1; T Cmax > 2500 ng/dL for Andro-gel after 90days | 1.1 percentage of actual number of subjects |
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.
Time frame: Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.
Population: Safety Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic systolic BP - 180 day | 1.89 mmHg | Standard Deviation 10.174 |
| SOV2012-F1 Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic systolic BP - 365 day | 2.75 mmHg | Standard Deviation 9.501 |
| SOV2012-F1 Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic diastolic BP - Baseline | 78.88 mmHg | Standard Deviation 6.34 |
| SOV2012-F1 Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic diastolic BP - 90 day | 0.58 mmHg | Standard Deviation 6.8 |
| SOV2012-F1 Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic systolic BP - Baseline | 125.8 mmHg | Standard Deviation 9.122 |
| SOV2012-F1 Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic systolic BP - 90 day | 2.16 mmHg | Standard Deviation 10.4 |
| SOV2012-F1 Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic diastolic BP - 180 day | 0.67 mmHg | Standard Deviation 6.014 |
| SOV2012-F1 Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic diastolic BP - 365 day | 1.14 mmHg | Standard Deviation 6.119 |
| Andro-gel™ Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic diastolic BP - 365 day | 1.75 mmHg | Standard Deviation 7.213 |
| Andro-gel™ Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic systolic BP - 180 day | 1.91 mmHg | Standard Deviation 9.044 |
| Andro-gel™ Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic systolic BP - Baseline | 125.95 mmHg | Standard Deviation 10.13 |
| Andro-gel™ Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic systolic BP - 365 day | 3.38 mmHg | Standard Deviation 10.492 |
| Andro-gel™ Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic diastolic BP - 180 day | 2.60 mmHg | Standard Deviation 6.826 |
| Andro-gel™ Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic diastolic BP - Baseline | 79.19 mmHg | Standard Deviation 6.624 |
| Andro-gel™ Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic systolic BP - 90 day | 3.07 mmHg | Standard Deviation 9.797 |
| Andro-gel™ Treated | Change From Baseline in Blood Pressures After Oral Testosterone Undecanoate and Testosterone Gel | Clinic diastolic BP - 90 day | 1.10 mmHg | Standard Deviation 8.262 |
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.
Time frame: Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.
Population: Safety Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change From Baseline in Fasting Insulin Concentration | Visit 8 - Day 90 | 3.59 uU/mL | Standard Deviation 56.11 |
| SOV2012-F1 Treated | Change From Baseline in Fasting Insulin Concentration | Visit 12 - Day 270 | 5.12 uU/mL | Standard Deviation 63.889 |
| SOV2012-F1 Treated | Change From Baseline in Fasting Insulin Concentration | Visit 10 - Day 180 | 2.77 uU/mL | Standard Deviation 54.045 |
| SOV2012-F1 Treated | Change From Baseline in Fasting Insulin Concentration | End of Treatment | -5.24 uU/mL | Standard Deviation 43.047 |
| SOV2012-F1 Treated | Change From Baseline in Fasting Insulin Concentration | Baseline | 27.30 uU/mL | Standard Deviation 38.03 |
| Andro-gel™ Treated | Change From Baseline in Fasting Insulin Concentration | End of Treatment | -2.58 uU/mL | Standard Deviation 14.967 |
| Andro-gel™ Treated | Change From Baseline in Fasting Insulin Concentration | Baseline | 24.83 uU/mL | Standard Deviation 18.555 |
| Andro-gel™ Treated | Change From Baseline in Fasting Insulin Concentration | Visit 8 - Day 90 | 2.43 uU/mL | Standard Deviation 19.328 |
| Andro-gel™ Treated | Change From Baseline in Fasting Insulin Concentration | Visit 10 - Day 180 | 5.12 uU/mL | Standard Deviation 46.035 |
| Andro-gel™ Treated | Change From Baseline in Fasting Insulin Concentration | Visit 12 - Day 270 | 0.54 uU/mL | Standard Deviation 20.026 |
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.
Time frame: Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.
Population: Safety Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change From Baseline in Fasting Serum Glucose (FSG) Concentration | Visit 8 - Day 90 | 4.2 mg/dL | Standard Deviation 24.84 |
| SOV2012-F1 Treated | Change From Baseline in Fasting Serum Glucose (FSG) Concentration | Visit 12 - Day 270 | 1.4 mg/dL | Standard Deviation 21.82 |
| SOV2012-F1 Treated | Change From Baseline in Fasting Serum Glucose (FSG) Concentration | Visit 10 - Day 180 | 1.4 mg/dL | Standard Deviation 24.54 |
| SOV2012-F1 Treated | Change From Baseline in Fasting Serum Glucose (FSG) Concentration | End of Treatment | -4.7 mg/dL | Standard Deviation 20.41 |
| SOV2012-F1 Treated | Change From Baseline in Fasting Serum Glucose (FSG) Concentration | Baseline | 108.6 mg/dL | Standard Deviation 31.19 |
| Andro-gel™ Treated | Change From Baseline in Fasting Serum Glucose (FSG) Concentration | End of Treatment | -0.8 mg/dL | Standard Deviation 21.61 |
| Andro-gel™ Treated | Change From Baseline in Fasting Serum Glucose (FSG) Concentration | Baseline | 110.3 mg/dL | Standard Deviation 26.01 |
| Andro-gel™ Treated | Change From Baseline in Fasting Serum Glucose (FSG) Concentration | Visit 8 - Day 90 | 3.0 mg/dL | Standard Deviation 23.51 |
| Andro-gel™ Treated | Change From Baseline in Fasting Serum Glucose (FSG) Concentration | Visit 10 - Day 180 | 2.4 mg/dL | Standard Deviation 21.48 |
| Andro-gel™ Treated | Change From Baseline in Fasting Serum Glucose (FSG) Concentration | Visit 12 - Day 270 | 6.2 mg/dL | Standard Deviation 31.97 |
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%.
Time frame: Baseline (Day 1, pre-treatment) and the change from baseline at the End of Treatment
Population: Safety Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change From Baseline in Hematology Parameters | HbA1c with diabetes mellitus (baseline) | 7.20 percentage of HbA1c | Standard Deviation 0.515 |
| SOV2012-F1 Treated | Change From Baseline in Hematology Parameters | HbA1c without diabetes mellitus (baseline) | 5.63 percentage of HbA1c | Standard Deviation 0.432 |
| SOV2012-F1 Treated | Change From Baseline in Hematology Parameters | HbA1c without diabetes mellitus end of treatment | 0.11 percentage of HbA1c | Standard Deviation 0.369 |
| SOV2012-F1 Treated | Change From Baseline in Hematology Parameters | HbA1c with diabetes mellitus end of treatment | 0.04 percentage of HbA1c | Standard Deviation 0.975 |
| Andro-gel™ Treated | Change From Baseline in Hematology Parameters | HbA1c without diabetes mellitus end of treatment | 0.00 percentage of HbA1c | Standard Deviation 0.326 |
| Andro-gel™ Treated | Change From Baseline in Hematology Parameters | HbA1c with diabetes mellitus (baseline) | 7.07 percentage of HbA1c | Standard Deviation 0.34 |
| Andro-gel™ Treated | Change From Baseline in Hematology Parameters | HbA1c with diabetes mellitus end of treatment | 0.73 percentage of HbA1c | Standard Deviation 0.608 |
| Andro-gel™ Treated | Change From Baseline in Hematology Parameters | HbA1c without diabetes mellitus (baseline) | 5.65 percentage of HbA1c | Standard Deviation 0.469 |
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.
Time frame: Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment
Population: Safety set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change From Baseline in Hormone Levels | Follicle Stimulating Hormone (FSH) - Baseline | 5.46 mIU/mL | Standard Deviation 5.496 |
| SOV2012-F1 Treated | Change From Baseline in Hormone Levels | Follicle Stimulating Hormone (FSH) - Visit 8 - Day 90 | -3.35 mIU/mL | Standard Deviation 4.423 |
| SOV2012-F1 Treated | Change From Baseline in Hormone Levels | Follicle Stimulating Hormone (FSH) - Visit Day 365 | -2.72 mIU/mL | Standard Deviation 4.209 |
| SOV2012-F1 Treated | Change From Baseline in Hormone Levels | Follicle Stimulating Hormone (FSH) - Visit Day 365 End of Treatment | -2.45 mIU/mL | Standard Deviation 4.162 |
| SOV2012-F1 Treated | Change From Baseline in Hormone Levels | Luteinizing Hormone (LH) - Baseline | 4.82 mIU/mL | Standard Deviation 3.755 |
| SOV2012-F1 Treated | Change From Baseline in Hormone Levels | Luteinizing Hormone (LH) - Visit 8 - Day 90 | -3.25 mIU/mL | Standard Deviation 3.805 |
| SOV2012-F1 Treated | Change From Baseline in Hormone Levels | Luteinizing Hormone (LH) - Visit Day 365 | -2.53 mIU/mL | Standard Deviation 3.487 |
| SOV2012-F1 Treated | Change From Baseline in Hormone Levels | Luteinizing Visit Day Hormone (LH) - End of Treatment | -2.18 mIU/mL | Standard Deviation 3.582 |
| Andro-gel™ Treated | Change From Baseline in Hormone Levels | Luteinizing Visit Day Hormone (LH) - End of Treatment | -1.60 mIU/mL | Standard Deviation 4.272 |
| Andro-gel™ Treated | Change From Baseline in Hormone Levels | Follicle Stimulating Hormone (FSH) - Baseline | 5.03 mIU/mL | Standard Deviation 3.283 |
| Andro-gel™ Treated | Change From Baseline in Hormone Levels | Luteinizing Hormone (LH) - Baseline | 4.58 mIU/mL | Standard Deviation 2.494 |
| Andro-gel™ Treated | Change From Baseline in Hormone Levels | Follicle Stimulating Hormone (FSH) - Visit 8 - Day 90 | -3.28 mIU/mL | Standard Deviation 2.888 |
| Andro-gel™ Treated | Change From Baseline in Hormone Levels | Luteinizing Hormone (LH) - Visit Day 365 | -1.67 mIU/mL | Standard Deviation 4.484 |
| Andro-gel™ Treated | Change From Baseline in Hormone Levels | Follicle Stimulating Hormone (FSH) - Visit Day 365 | -1.82 mIU/mL | Standard Deviation 6.708 |
| Andro-gel™ Treated | Change From Baseline in Hormone Levels | Luteinizing Hormone (LH) - Visit 8 - Day 90 | -3.28 mIU/mL | Standard Deviation 2.472 |
| Andro-gel™ Treated | Change From Baseline in Hormone Levels | Follicle Stimulating Hormone (FSH) - Visit Day 365 End of Treatment | -1.77 mIU/mL | Standard Deviation 6.23 |
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.
Time frame: Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270, Day 365 and the End of Treatment
Population: Safety Set LDL Cholesterol, Baseline = number of subjects with non-missing results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | Cholesterol, End of Treatment | -11.6 mg/dL | Standard Deviation 30.56 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | LDL Cholesterol, Baseline 1 | 110.8 mg/dL | Standard Deviation 34.72 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | Cholesterol, Baseline | 190.5 mg/dL | Standard Deviation 38.55 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | LDL Cholesterol, Visit 8 - Day 90 | -0.3 mg/dL | Standard Deviation 26.13 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | HDL Cholesterol, Baseline | 46.8 mg/dL | Standard Deviation 11.84 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | LDL Cholesterol, Visit 10 - Day 180 | -3.1 mg/dL | Standard Deviation 25.79 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | Cholesterol, Visit 10 Day 180 | -10.7 mg/dL | Standard Deviation 29.56 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | LDL Cholesterol, Visit 12 - Day 270 | -6.1 mg/dL | Standard Deviation 27.9 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | HDL Cholesterol, Visit 8, Day 90 | -7.5 mg/dL | Standard Deviation 8.45 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | LDL Cholesterol, Visit Day 365 | -4.8 mg/dL | Standard Deviation 25.06 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | Cholesterol, Visit 12 Day 270 | -14.3 mg/dL | Standard Deviation 32.28 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | LDL Cholesterol, End of Treatment | -3.8 mg/dL | Standard Deviation 25.92 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | HDL Cholesterol, Visit 10, Day 180 | -6.9 mg/dL | Standard Deviation 9.96 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | Triglycerides, Baseline | 167.6 mg/dL | Standard Deviation 86.3 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | Triglycerides, Visit 8 - Day 90 | -2.5 mg/dL | Standard Deviation 86.21 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | HDL Cholesterol, Visit 12, Day 270 | -6.7 mg/dL | Standard Deviation 9.53 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | Triglycerides, Visit 10 - Day 180 | -3.2 mg/dL | Standard Deviation 75.75 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | Cholesterol, Visit Day 365 | -14.0 mg/dL | Standard Deviation 28.72 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | Triglycerides, Visit 12 - Day 270 | -8.0 mg/dL | Standard Deviation 88.6 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | HDL Cholesterol, Visit Day 365 | -7.9 mg/dL | Standard Deviation 9.83 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | Triglycerides, Visit Day 365 | -7.0 mg/dL | Standard Deviation 73.84 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | Cholesterol, Visit 8 Day 90 | -8.6 mg/dL | Standard Deviation 29.86 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | Triglycerides, End of Treatment | -4.8 mg/dL | Standard Deviation 77.97 |
| SOV2012-F1 Treated | Change From Baseline in Lipid Profiles | HDL Cholesterol, End of Treatment | -7.1 mg/dL | Standard Deviation 9.87 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | Triglycerides, End of Treatment | 25.9 mg/dL | Standard Deviation 136.57 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | Cholesterol, Baseline | 191.1 mg/dL | Standard Deviation 39.12 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | Cholesterol, Visit 8 Day 90 | -6.1 mg/dL | Standard Deviation 26.36 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | Cholesterol, Visit 12 Day 270 | -8.2 mg/dL | Standard Deviation 31.83 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | Cholesterol, Visit Day 365 | -5.5 mg/dL | Standard Deviation 38.41 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | Cholesterol, End of Treatment | -6.0 mg/dL | Standard Deviation 36.24 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | HDL Cholesterol, Baseline | 45.2 mg/dL | Standard Deviation 11.33 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | HDL Cholesterol, Visit 8, Day 90 | -1.5 mg/dL | Standard Deviation 6.79 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | HDL Cholesterol, Visit 10, Day 180 | -1.9 mg/dL | Standard Deviation 6.94 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | HDL Cholesterol, Visit 12, Day 270 | -1.6 mg/dL | Standard Deviation 7.62 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | HDL Cholesterol, Visit Day 365 | -2.8 mg/dL | Standard Deviation 7.12 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | HDL Cholesterol, End of Treatment | -2.8 mg/dL | Standard Deviation 7.05 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | LDL Cholesterol, Baseline 1 | 108.9 mg/dL | Standard Deviation 34.39 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | LDL Cholesterol, Visit 8 - Day 90 | -4.3 mg/dL | Standard Deviation 22.91 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | LDL Cholesterol, Visit 10 - Day 180 | -5.4 mg/dL | Standard Deviation 21.92 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | LDL Cholesterol, Visit 12 - Day 270 | -5.4 mg/dL | Standard Deviation 26.84 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | LDL Cholesterol, Visit Day 365 | -5.4 mg/dL | Standard Deviation 30.42 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | LDL Cholesterol, End of Treatment | -5.5 mg/dL | Standard Deviation 29.41 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | Triglycerides, Baseline | 184.6 mg/dL | Standard Deviation 86.79 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | Triglycerides, Visit 8 - Day 90 | 9.4 mg/dL | Standard Deviation 100.18 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | Triglycerides, Visit 10 - Day 180 | 19.0 mg/dL | Standard Deviation 99.18 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | Triglycerides, Visit 12 - Day 270 | 15.4 mg/dL | Standard Deviation 126.56 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | Triglycerides, Visit Day 365 | 26.0 mg/dL | Standard Deviation 144.41 |
| Andro-gel™ Treated | Change From Baseline in Lipid Profiles | Cholesterol, Visit 10 Day 180 | -5.7 mg/dL | Standard Deviation 25.07 |
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. The reported value is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value. A positive value for Change in Baseline represents an increase in the liver function test value
Time frame: Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.
Population: Safety set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Alkaline Phosphatase (Baseline) | 72.8 U/L | Standard Deviation 18.79 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Alkaline Phosphatase (Visit 8 - Day 90) | -6.0 U/L | Standard Deviation 11.03 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Alkaline Phosphatase (Visit 10 - Day 180) | -4.2 U/L | Standard Deviation 12.14 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Alkaline Phosphatase (Visit 12 - Day 270) | -5.5 U/L | Standard Deviation 10.57 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Alkaline Phosphatase (Visit Day 365) | -4.5 U/L | Standard Deviation 11.42 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Alkaline Phosphatase (End of Treatment) | -4.0 U/L | Standard Deviation 11.31 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Alanine Aminotransferase (ALT) - Baseline | 30.5 U/L | Standard Deviation 13.59 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Alanine Aminotransferase (ALT), Visit 8 - Day 90 | -2.6 U/L | Standard Deviation 14.28 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Alanine Aminotransferase (ALT), Visit 10 - Day 180 | -2.9 U/L | Standard Deviation 11.44 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Alanine Aminotransferase (ALT), Visit 12 - Day 270 | -2.2 U/L | Standard Deviation 12.76 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Alanine Aminotransferase (ALT), Visit Day 365 | -1.4 U/L | Standard Deviation 12.89 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Alanine Aminotransferase (ALT) - End of Treatment | -0.4 U/L | Standard Deviation 19.84 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Aspartate Aminotransferase (AST) - Baseline | 23.8 U/L | Standard Deviation 8.83 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Aspartate Aminotransferase (AST) - Visit 8, Day 90 | 0.8 U/L | Standard Deviation 10.96 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Aspartate Aminotransferase (AST) - Visit 10, Day 180 | 0.1 U/L | Standard Deviation 8.04 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Aspartate Aminotransferase (AST) - Visit 12, Day 270 | 0.0 U/L | Standard Deviation 9.03 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Aspartate Aminotransferase (AST) - Visit Day 365 | 2.2 U/L | Standard Deviation 27.18 |
| SOV2012-F1 Treated | Change From Baseline in Liver Function Tests | Aspartate Aminotransferase (AST) - End of Treatment | 2.4 U/L | Standard Deviation 27.18 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Aspartate Aminotransferase (AST) - Visit 8, Day 90 | 1.2 U/L | Standard Deviation 8.34 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Alkaline Phosphatase (Baseline) | 74.0 U/L | Standard Deviation 20.19 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Alanine Aminotransferase (ALT), Visit 12 - Day 270 | 0.7 U/L | Standard Deviation 17.25 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Alkaline Phosphatase (Visit 8 - Day 90) | -1.2 U/L | Standard Deviation 8.9 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Aspartate Aminotransferase (AST) - End of Treatment | 1.0 U/L | Standard Deviation 9.69 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Alkaline Phosphatase (Visit 10 - Day 180) | -1.6 U/L | Standard Deviation 10.13 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Alanine Aminotransferase (ALT), Visit Day 365 | 1.3 U/L | Standard Deviation 14.55 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Alkaline Phosphatase (Visit 12 - Day 270) | -2.1 U/L | Standard Deviation 9.96 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Aspartate Aminotransferase (AST) - Visit 10, Day 180 | 1.7 U/L | Standard Deviation 12.24 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Alkaline Phosphatase (Visit Day 365) | -1.5 U/L | Standard Deviation 10.38 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Alanine Aminotransferase (ALT) - End of Treatment | 0.9 U/L | Standard Deviation 14.64 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Alkaline Phosphatase (End of Treatment) | -1.5 U/L | Standard Deviation 10.37 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Aspartate Aminotransferase (AST) - Visit Day 365 | 1.2 U/L | Standard Deviation 9.64 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Alanine Aminotransferase (ALT) - Baseline | 31.0 U/L | Standard Deviation 12.64 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Aspartate Aminotransferase (AST) - Baseline | 23.4 U/L | Standard Deviation 8.04 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Alanine Aminotransferase (ALT), Visit 8 - Day 90 | -0.0 U/L | Standard Deviation 13.3 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Aspartate Aminotransferase (AST) - Visit 12, Day 270 | 0.3 U/L | Standard Deviation 11.27 |
| Andro-gel™ Treated | Change From Baseline in Liver Function Tests | Alanine Aminotransferase (ALT), Visit 10 - Day 180 | 0.9 U/L | Standard Deviation 16.64 |
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. The reported value is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value. A positive value for Change in Baseline represents an increase in the PSA value.
Time frame: Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270, Day 365 and the End of Treatment
Population: Safety Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change From Baseline in PSA | Prostate Specific Antigen, Baseline | 0.87 ng/mL | Standard Deviation 0.549 |
| SOV2012-F1 Treated | Change From Baseline in PSA | Prostate Specific Antigen, Visit 8 - Day 90 | 0.18 ng/mL | Standard Deviation 0.452 |
| SOV2012-F1 Treated | Change From Baseline in PSA | Prostate Specific Antigen, Visit 10 - Day 180 | 0.20 ng/mL | Standard Deviation 0.472 |
| SOV2012-F1 Treated | Change From Baseline in PSA | Prostate Specific Antigen, Visit 12 - Day 270 | 0.25 ng/mL | Standard Deviation 0.586 |
| SOV2012-F1 Treated | Change From Baseline in PSA | Prostate Specific Antigen, Visit Day 365 | 0.23 ng/mL | Standard Deviation 0.525 |
| SOV2012-F1 Treated | Change From Baseline in PSA | Prostate Specific Antigen, End of Treatment | 0.23 ng/mL | Standard Deviation 0.523 |
| Andro-gel™ Treated | Change From Baseline in PSA | Prostate Specific Antigen, Visit Day 365 | 0.27 ng/mL | Standard Deviation 0.756 |
| Andro-gel™ Treated | Change From Baseline in PSA | Prostate Specific Antigen, Baseline | 0.78 ng/mL | Standard Deviation 0.506 |
| Andro-gel™ Treated | Change From Baseline in PSA | Prostate Specific Antigen, Visit 12 - Day 270 | 0.29 ng/mL | Standard Deviation 0.65 |
| Andro-gel™ Treated | Change From Baseline in PSA | Prostate Specific Antigen, Visit 8 - Day 90 | 0.18 ng/mL | Standard Deviation 0.435 |
| Andro-gel™ Treated | Change From Baseline in PSA | Prostate Specific Antigen, End of Treatment | 0.41 ng/mL | Standard Deviation 1.688 |
| Andro-gel™ Treated | Change From Baseline in PSA | Prostate Specific Antigen, Visit 10 - Day 180 | 0.22 ng/mL | Standard Deviation 0.533 |
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.
Time frame: Baseline (Day 1, pre-treatment) and change from baseline at the End of Treatment (EOT)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change From Baseline in the IIEF | Intercourse Satisfaction (End of Treatment) | 2.4 score on a scale | Standard Deviation 4.56 |
| SOV2012-F1 Treated | Change From Baseline in the IIEF | Sexual Desire (Baseline) | 3.6 score on a scale | Standard Deviation 1.12 |
| SOV2012-F1 Treated | Change From Baseline in the IIEF | Intercourse Satisfaction (Baseline) | 8.4 score on a scale | Standard Deviation 5.17 |
| SOV2012-F1 Treated | Change From Baseline in the IIEF | Sexual Desire (End of Treatment) | 0.7 score on a scale | Standard Deviation 1.25 |
| SOV2012-F1 Treated | Change From Baseline in the IIEF | Orgasmic Function (Baseline) | 7.3 score on a scale | Standard Deviation 3.45 |
| SOV2012-F1 Treated | Change From Baseline in the IIEF | Overall Satisfaction (Baseline) | 4.8 score on a scale | Standard Deviation 2.31 |
| SOV2012-F1 Treated | Change From Baseline in the IIEF | Overall Satisfaction Visit Day 365 | 2.3 score on a scale | Standard Deviation 2.55 |
| SOV2012-F1 Treated | Change From Baseline in the IIEF | Erectile Function (End of Treatment) | 5.1 score on a scale | Standard Deviation 8.3 |
| SOV2012-F1 Treated | Change From Baseline in the IIEF | Orgasmic Function (End of Treatment) | 1.5 score on a scale | Standard Deviation 3.61 |
| SOV2012-F1 Treated | Change From Baseline in the IIEF | Erectile Function (Baseline) | 19.8 score on a scale | Standard Deviation 8.99 |
| Andro-gel™ Treated | Change From Baseline in the IIEF | Overall Satisfaction (Baseline) | 4.1 score on a scale | Standard Deviation 2.27 |
| Andro-gel™ Treated | Change From Baseline in the IIEF | Erectile Function (End of Treatment) | 4.1 score on a scale | Standard Deviation 8.35 |
| Andro-gel™ Treated | Change From Baseline in the IIEF | Intercourse Satisfaction (Baseline) | 6.8 score on a scale | Standard Deviation 5.55 |
| Andro-gel™ Treated | Change From Baseline in the IIEF | Intercourse Satisfaction (End of Treatment) | 2.4 score on a scale | Standard Deviation 4.81 |
| Andro-gel™ Treated | Change From Baseline in the IIEF | Orgasmic Function (Baseline) | 6.7 score on a scale | Standard Deviation 3.42 |
| Andro-gel™ Treated | Change From Baseline in the IIEF | Orgasmic Function (End of Treatment) | 2.4 score on a scale | Standard Deviation 4.81 |
| Andro-gel™ Treated | Change From Baseline in the IIEF | Sexual Desire (Baseline) | 3.7 score on a scale | Standard Deviation 1.1 |
| Andro-gel™ Treated | Change From Baseline in the IIEF | Sexual Desire (End of Treatment) | 0.9 score on a scale | Standard Deviation 1.1 |
| Andro-gel™ Treated | Change From Baseline in the IIEF | Overall Satisfaction Visit Day 365 | 1.6 score on a scale | Standard Deviation 2.83 |
| Andro-gel™ Treated | Change From Baseline in the IIEF | Erectile Function (Baseline) | 17.1 score on a scale | Standard Deviation 9.62 |
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.
Time frame: Baseline (pre-treatment) to 90 days and 365 days
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change From Baseline in the IPSS | Baseline | 4.4 score on a scale | Standard Deviation 4.12 |
| SOV2012-F1 Treated | Change From Baseline in the IPSS | Change from baseline (Visit 8 - Day 90) | 0.2 score on a scale | Standard Deviation 3.56 |
| SOV2012-F1 Treated | Change From Baseline in the IPSS | Change from baseline (Visit Day 365) | 0.6 score on a scale | Standard Deviation 3.99 |
| Andro-gel™ Treated | Change From Baseline in the IPSS | Baseline | 5.4 score on a scale | Standard Deviation 4.94 |
| Andro-gel™ Treated | Change From Baseline in the IPSS | Change from baseline (Visit 8 - Day 90) | 0.7 score on a scale | Standard Deviation 3.72 |
| Andro-gel™ Treated | Change From Baseline in the IPSS | Change from baseline (Visit Day 365) | 1.0 score on a scale | Standard Deviation 3.73 |
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.
Time frame: Baseline (pre-treatment) to 90 days and 365 days
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | With a Partner Visit 8 - Day 90 | 1.168 score on a scale | Standard Deviation 1.7335 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Overall Level of sexual desire Visit Day 365 | 1.552 score on a scale | Standard Deviation 1.7596 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Without a Partner Visit 3 - Day 1 (baseline) | 0.754 score on a scale | Standard Deviation 0.964 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Without a Partner Visit 8 - Day 90 | 0.742 score on a scale | Standard Deviation 1.6478 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Without a Partner Visit Day 365 | 0.920 score on a scale | Standard Deviation 1.5566 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | With a Partner Visit 3 - Day 1 (baseline) | 0.954 score on a scale | Standard Deviation 1.2033 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Overall Level of sexual desire Visit 8 - Day 90 | 1.674 score on a scale | Standard Deviation 1.6851 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | With a Partner Visit Day 365 | 1.106 score on a scale | Standard Deviation 1.667 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Negative Mood Visit 3 - Day 1 (baseline) | 9.258 score on a scale | Standard Deviation 5.8557 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Negative Mood Visit 8 - Day 90 | -2.205 score on a scale | Standard Deviation 5.6199 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Negative Mood Visit Day 365 | -3.011 score on a scale | Standard Deviation 5.3399 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Positive mood - Visit 3 - Day 1 (baseline) | 16.799 score on a scale | Standard Deviation 5.1778 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Positive mood - Visit 8 - Day 90 | 2.513 score on a scale | Standard Deviation 5.0149 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Sexual Activity Score Visit 8 - Day 90 | 12.284 score on a scale | Standard Deviation 15.9338 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Sexual Activity Score Day 365 | 12.009 score on a scale | Standard Deviation 16.5438 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Erection Grade, Visit 3 - Day 1 (baseline) | 32.145 score on a scale | Standard Deviation 22.9941 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Erection Grade, Visit 8 - Day 90 | 17.494 score on a scale | Standard Deviation 25.0678 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Erection Grade, Day 365 | 14.235 score on a scale | Standard Deviation 28.9806 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Erection Duration, Visit 3 - Day 1 (baseline) | 1.985 score on a scale | Standard Deviation 1.4894 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Erection Duration, Visit 8 - Day 90 | 1.480 score on a scale | Standard Deviation 1.7137 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Erection Duration, Day 365 | 1.300 score on a scale | Standard Deviation 1.842 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Overall Level of sexual desire Visit 3 - Day 1 (baseline) | 1.990 score on a scale | Standard Deviation 1.4195 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Positive mood - Day 365 | 3.407 score on a scale | Standard Deviation 5.1065 |
| SOV2012-F1 Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Sexual Activity Score Visit 3 - Day 1 (baseline) | 15.314 score on a scale | Standard Deviation 13.8521 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Erection Grade, Visit 3 - Day 1 (baseline) | 30.652 score on a scale | Standard Deviation 23.9078 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Overall Level of sexual desire Visit 8 - Day 90 | 1.256 score on a scale | Standard Deviation 1.5583 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Positive mood - Visit 8 - Day 90 | 3.347 score on a scale | Standard Deviation 5.2716 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Overall Level of sexual desire Visit Day 365 | 1.372 score on a scale | Standard Deviation 1.6968 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Positive mood - Day 365 | 2.817 score on a scale | Standard Deviation 5.1714 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Without a Partner Visit 3 - Day 1 (baseline) | 0.875 score on a scale | Standard Deviation 1.1397 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Erection Duration, Visit 3 - Day 1 (baseline) | 1.814 score on a scale | Standard Deviation 1.5321 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Without a Partner Visit 8 - Day 90 | 0.498 score on a scale | Standard Deviation 1.2075 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Sexual Activity Score Visit 8 - Day 90 | 10.951 score on a scale | Standard Deviation 17.4041 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Without a Partner Visit Day 365 | 0.769 score on a scale | Standard Deviation 1.584 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Overall Level of sexual desire Visit 3 - Day 1 (baseline) | 2.039 score on a scale | Standard Deviation 1.5659 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | With a Partner Visit 3 - Day 1 (baseline) | 0.840 score on a scale | Standard Deviation 1.2928 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Sexual Activity Score Day 365 | 12.591 score on a scale | Standard Deviation 17.7272 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | With a Partner Visit 8 - Day 90 | 0.594 score on a scale | Standard Deviation 1.7373 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Erection Duration, Visit 8 - Day 90 | 1.012 score on a scale | Standard Deviation 1.7166 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | With a Partner Visit Day 365 | 0.760 score on a scale | Standard Deviation 1.8284 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Sexual Activity Score Visit 3 - Day 1 (baseline) | 12.581 score on a scale | Standard Deviation 12.0706 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Negative Mood Visit 3 - Day 1 (baseline) | 9.847 score on a scale | Standard Deviation 5.0938 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Erection Grade, Visit 8 - Day 90 | 12.619 score on a scale | Standard Deviation 22.6952 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Negative Mood Visit 8 - Day 90 | -1.886 score on a scale | Standard Deviation 5.567 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Erection Duration, Day 365 | 1.501 score on a scale | Standard Deviation 1.6751 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Negative Mood Visit Day 365 | -1.435 score on a scale | Standard Deviation 5.7065 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Erection Grade, Day 365 | 17.584 score on a scale | Standard Deviation 23.167 |
| Andro-gel™ Treated | Change From Baseline in the Psychosexual Daily Questionnaire (PDQ) | Positive mood - Visit 3 - Day 1 (baseline) | 15.742 score on a scale | Standard Deviation 5.5015 |
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: 1. limitations in physical activities because of health problems 2. limitations in social activities because of physical or emotional problems 3. limitations in usual role activities because of physical health problems 4. bodily pain 5. general mental health (psychological distress and well-being) 6. limitations in usual role activities because of emotional problems 7. vitality (energy and fatigue) 8. general health perceptions. Each domain is scored from 0-100 with a score of 0 = maximum disability and a score of 100 = no disability. End of Treatment (EOT) occurred either at time of early withdrawal from the study or at Day 365. The reported value is the change from baseline. A positive value at EOT indicates improvement in the measure towards less disability. The EOT Change from Baseline is simply the arithmetic difference between the Baseline and EOT scores.
Time frame: Baseline (Day 1, pre-treatment) and change from baseline at the End of Treatment (EOT)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Health Change (Baseline) | 65.2 score on a scale | Standard Deviation 20.66 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Emotional Well-being (End of Treatment) | 7.1 score on a scale | Standard Deviation 15.44 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | General Health (End of Treatment) | 3.5 score on a scale | Standard Deviation 16.87 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Health Change (End of Treatment) | 14.6 score on a scale | Standard Deviation 26.81 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Pain (Baseline) | 77.17 score on a scale | Standard Deviation 21.103 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Pain (End of Treatment) | 4.16 score on a scale | — |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Physical Functioning (Baseline) | 85.5 score on a scale | Standard Deviation 19.03 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Physical Functioning (End of Treatment) | 3.6 score on a scale | Standard Deviation 17.57 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Role Limitations due to Emotional Problems (Baseline) | 85.317 score on a scale | Standard Deviation 30.2358 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Role Limitations due to Emotional Problems (End of Treatment) | 12.081 score on a scale | Standard Deviation 39.3671 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Role Limitations due to Physical Health (Baseline) | 82.1 score on a scale | Standard Deviation 31.09 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Role Limitations due to Physical Health (End of Treatment) | 12.4 score on a scale | Standard Deviation 41.06 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Social Functioning (Baseline) | 84.75 score on a scale | Standard Deviation 18.527 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Social Functioning (End of Treatment) | 9.31 score on a scale | Standard Deviation 22.14 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Mental Health Composite (Baseline) | 51.885 score on a scale | Standard Deviation 8.6492 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Mental Health Composite (End of Treatment) | 5.478 score on a scale | Standard Deviation 9.8093 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Physical Health Composite (Baseline) | 49.229 score on a scale | Standard Deviation 8.3286 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Physical Health Composite (End of Treatment) | 1.558 score on a scale | Standard Deviation 7.5381 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Emotional Well-being (Baseline) | 72.4 score on a scale | Standard Deviation 17.55 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Energy/Fatigue (Baseline) | 61.0 score on a scale | Standard Deviation 20.22 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | Energy/Fatigue (End of Treatment) | 16.6 score on a scale | Standard Deviation 21 |
| SOV2012-F1 Treated | Change From Baseline in the SF-36 | General Health (Baseline) | 69.0 score on a scale | Standard Deviation 17.09 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Physical Health Composite (Baseline) | 48.002 score on a scale | Standard Deviation 8.7737 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Mental Health Composite (Baseline) | 49.025 score on a scale | Standard Deviation 10.5313 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Energy/Fatigue (Baseline) | 53.0 score on a scale | Standard Deviation 21.91 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Role Limitations due to Physical Health (End of Treatment) | 14.3 score on a scale | Standard Deviation 39.67 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | General Health (End of Treatment) | 6.9 score on a scale | Standard Deviation 15.46 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Health Change (Baseline) | 59.6 score on a scale | Standard Deviation 18.66 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | General Health (Baseline) | 67.0 score on a scale | Standard Deviation 18.33 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Health Change (End of Treatment) | 7.0 score on a scale | Standard Deviation 24.16 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Social Functioning (Baseline) | 83.73 score on a scale | Standard Deviation 18.799 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Pain (Baseline) | 70.57 score on a scale | Standard Deviation 22.619 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Physical Health Composite (End of Treatment) | 2.968 score on a scale | Standard Deviation 8.1428 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Pain (End of Treatment) | 1.43 score on a scale | Standard Deviation 21.834 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Social Functioning (End of Treatment) | 6.83 score on a scale | Standard Deviation 22.161 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Physical Functioning (Baseline) | 83.3 score on a scale | Standard Deviation 19.05 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Energy/Fatigue (End of Treatment) | 15.5 score on a scale | Standard Deviation 21.12 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Physical Functioning (End of Treatment) | 6.8 score on a scale | Standard Deviation 19.82 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Emotional Well-being (End of Treatment) | 5.6 score on a scale | Standard Deviation 15.37 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Role Limitations due to Emotional Problems (Baseline) | 79.116 score on a scale | Standard Deviation 34.4177 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Mental Health Composite (End of Treatment) | 3.515 score on a scale | Standard Deviation 9.1373 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Role Limitations due to Emotional Problems (End of Treatment) | 5.778 score on a scale | Standard Deviation 35.2483 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Emotional Well-being (Baseline) | 68.0 score on a scale | Standard Deviation 18.98 |
| Andro-gel™ Treated | Change From Baseline in the SF-36 | Role Limitations due to Physical Health (Baseline) | 75.0 score on a scale | Standard Deviation 35.14 |
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. The reported value is the change from baseline. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value. A positive value for Change in Baseline represents an increase in the bilirubin value.
Time frame: Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, Day 180, Day 270 and the End of Treatment.
Population: Safety set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change in Bilirubin | Bilirubin, Visit 12 - Day 270 | 0.013 mg/dL | Standard Deviation 0.2254 |
| SOV2012-F1 Treated | Change in Bilirubin | Bilirubin - Baseline | 0.491 mg/dL | Standard Deviation 0.2437 |
| SOV2012-F1 Treated | Change in Bilirubin | Bilirubin, Visit Day 365 | -0.027 mg/dL | Standard Deviation 0.2155 |
| SOV2012-F1 Treated | Change in Bilirubin | Bilirubin, Visit 10 - Day 180 | -0.007 mg/dL | Standard Deviation 0.235 |
| SOV2012-F1 Treated | Change in Bilirubin | Bilirubin, End of Treatment | -0.032 mg/dL | Standard Deviation 0.2157 |
| SOV2012-F1 Treated | Change in Bilirubin | Bilirubin, Visit 8 - Day 90 | -0.088 mg/dL | Standard Deviation 0.2024 |
| Andro-gel™ Treated | Change in Bilirubin | Bilirubin, End of Treatment | 0.026 mg/dL | Standard Deviation 0.2117 |
| Andro-gel™ Treated | Change in Bilirubin | Bilirubin, Visit 8 - Day 90 | -0.058 mg/dL | Standard Deviation 0.2231 |
| Andro-gel™ Treated | Change in Bilirubin | Bilirubin, Visit 10 - Day 180 | -0.004 mg/dL | Standard Deviation 0.2106 |
| Andro-gel™ Treated | Change in Bilirubin | Bilirubin, Visit 12 - Day 270 | 0.029 mg/dL | Standard Deviation 0.2171 |
| Andro-gel™ Treated | Change in Bilirubin | Bilirubin, Visit Day 365 | 0.038 mg/dL | Standard Deviation 0.2245 |
| Andro-gel™ Treated | Change in Bilirubin | Bilirubin - Baseline | 0.465 mg/dL | Standard Deviation 0.2561 |
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. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value at Day 90 or Day 365. A positive value for Change in Baseline represents an increase in the hormone level.
Time frame: Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment
Population: Safety Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change in Hormone SHBG | SHBG - Baseline | 27.08 nmol/L | Standard Deviation 11.958 |
| SOV2012-F1 Treated | Change in Hormone SHBG | SHBG - Day 90 | -8.99 nmol/L | Standard Deviation 8.167 |
| SOV2012-F1 Treated | Change in Hormone SHBG | SHBG - Day 365 | -7.00 nmol/L | Standard Deviation 9.326 |
| SOV2012-F1 Treated | Change in Hormone SHBG | SHBG - End of Treatment | -6.25 nmol/L | Standard Deviation 9.637 |
| Andro-gel™ Treated | Change in Hormone SHBG | SHBG - End of Treatment | 1.39 nmol/L | Standard Deviation 7.595 |
| Andro-gel™ Treated | Change in Hormone SHBG | SHBG - Baseline | 24.52 nmol/L | Standard Deviation 10.21 |
| Andro-gel™ Treated | Change in Hormone SHBG | SHBG - Day 365 | 1.60 nmol/L | Standard Deviation 8.126 |
| Andro-gel™ Treated | Change in Hormone SHBG | SHBG - Day 90 | 0.26 nmol/L | Standard Deviation 4.341 |
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. The Change from Baseline is simply the arithmetic difference between the Baseline and the measured value at Day 90 or Day 365. A positive value for Change in Baseline represents an increase in the TSH level.
Time frame: Baseline (Day 1, pre-treatment) and the change from baseline at Day 90, and the End of Treatment
Population: Safety Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Change in TSH (Thyrotropin) | Thyrotropin - Baseline | 2.212 mU/L | Standard Deviation 1.1941 |
| SOV2012-F1 Treated | Change in TSH (Thyrotropin) | Thyrotropin - Day 90 | 0.293 mU/L | Standard Deviation 1.014 |
| SOV2012-F1 Treated | Change in TSH (Thyrotropin) | Thyrotropin - Day 365 | 0.195 mU/L | Standard Deviation 1.1494 |
| SOV2012-F1 Treated | Change in TSH (Thyrotropin) | Thyrotropin - End of Treatment | 0.209 mU/L | Standard Deviation 1.1204 |
| Andro-gel™ Treated | Change in TSH (Thyrotropin) | Thyrotropin - End of Treatment | 0.081 mU/L | Standard Deviation 1.0571 |
| Andro-gel™ Treated | Change in TSH (Thyrotropin) | Thyrotropin - Baseline | 2.407 mU/L | Standard Deviation 1.2624 |
| Andro-gel™ Treated | Change in TSH (Thyrotropin) | Thyrotropin - Day 365 | 0.122 mU/L | Standard Deviation 1.008 |
| Andro-gel™ Treated | Change in TSH (Thyrotropin) | Thyrotropin - Day 90 | 0.343 mU/L | Standard Deviation 1.0773 |
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).
Time frame: 52 weeks
Population: ACTH Completers Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOV2012-F1 Treated | Effect of SOV2012-F1 on Adrenal Cortical Function as Assessed by Measuring the Cortisol Response to Synthetic ACTH at Baseline in Subjects | Maximum Serum Cortisol (Day 1 - Baseline) | 23.75 nmol/L | Standard Deviation 3.584 |
| SOV2012-F1 Treated | Effect of SOV2012-F1 on Adrenal Cortical Function as Assessed by Measuring the Cortisol Response to Synthetic ACTH at Baseline in Subjects | Maximum Serum Cortisol (Day 365 - End of Study) | 25.22 nmol/L | Standard Deviation 4.561 |
| Andro-gel™ Treated | Effect of SOV2012-F1 on Adrenal Cortical Function as Assessed by Measuring the Cortisol Response to Synthetic ACTH at Baseline in Subjects | Maximum Serum Cortisol (Day 1 - Baseline) | 25.68 nmol/L | Standard Deviation 2.373 |
| Andro-gel™ Treated | Effect of SOV2012-F1 on Adrenal Cortical Function as Assessed by Measuring the Cortisol Response to Synthetic ACTH at Baseline in Subjects | Maximum Serum Cortisol (Day 365 - End of Study) | 27.05 nmol/L | Standard Deviation 3.267 |