Long-term Safety Study of Intramuscular Injections of 750 mg and 1000 mg Testosterone Undecanoate in Hypogonadal Men

Study Overview
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Brief Summary
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To evaluate the pharmacokinetics of TU 750 mg and TU 1000 mg via multiple measurements of serum total testosterone.

Official Title
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A Two-Arm, Open-Label, Randomized, Multi-Center Pharmacokinetic and Long-Term Safety Study of Intramuscular Injections of 750 mg and 1000 mg Testosterone Undecanoate in Hypogonadal Men

Conditions
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Hypogonadism, Primary Hypogonadism, Secondary Hypogonadism

Intervention / Treatment
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* Drug: Testosterone Undecanoate 750 mg
* Drug: Testosterone Undecanoate 1000 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male with primary or secondary hypogonadism at least 18 years of age and for study part C2 weighs ≥143.3 lb (≥65 kg) Morning screening serum testosterone concentration <300 ng/dL Exclusion Criteria: American Urological Association (AUA) Symptom Score ≥15 or significant prostatic symptoms History of carcinoma, tumors or induration of the prostate or the male mammary gland including suspicion thereof Screening serum prostate-specific antigen (PSA) level >4 ng/mL or hyperplasia of the prostate (size >75 cm3 as measured by transrectal ultrasonography) Past or present liver tumors or acute or chronic hepatic disease with impairment of liver function; liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) exceeding 1.5 times upper limit of normal History of deep vein thrombosis in the past 5 years or any history of cerebrovascular accident Severe acne Hypertension (systolic blood pressure >160 mm Hg and diastolic blood pressure >95 mm Hg) or coronary heart disease not stabilized by therapy as assessed by the investigator Insulin-dependent diabetes mellitus or uncontrolled non-insulin-dependent diabetes mellitus; patients with diabetes are excluded if screening glycated hemoglobin (HbA1C) level is >9% Use of any sex hormones within 28 days (for injectable testosterone preparations) or 7 days (for oral, gel, patch, etc, testosterone preparations) prior to screening visit and throughout the study (exclusive of administered study drug) Use of steroidal anabolic drugs or supplements (eg, dehydroepiandrosterone [DHEA]) by any application method within the 28 days prior to first administration of study drug and throughout the study (exclusive of administrated study drug) Medication with substances which might interfere with testosterone metabolism within 28 days before the first administration of study drug History of sleep apnea Insulin-dependent diabetes mellitus Use of steroidal anabolic drugs or supplements by any application method within the 28-days prior to the first administration of the study drug and throughout the study (exclusive of the administered study drug)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>750 mg dose of testosterone undecanoate | Drug: Testosterone Undecanoate 750 mg<br> <br> |
| Experimental: 2<br>1000 mg dose testosterone undecanoate | Drug: Testosterone Undecanoate 1000 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Meeting Serum Total Testosterone Average Concentration Criteria for Responder During the 3rd Injection Interval in Part C | Responders were participants with serum total testosterone average concentration (Cavg) between 300 and 1000 ng/dL derived from the 3rd injection intensive pharmacokinetic (IPK) interval. | Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14 | 
| Serum Total Testosterone Average Concentration During the 3rd Injection Interval in Part C | Serum total testosterone Cavg derived from the 3rd injection IPK interval | Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14 | 
| Serum Total Testosterone Maximum Concentration During the 3rd Injection Interval in Part C | Serum total testosterone maximum concentration (Cmax) derived from the 3rd injection IPK interval | Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14 | 
| Serum Total Testosterone Concentration at the End of the Dosing Interval Following the 3rd Injection in Part C | Serum total testosterone concentration at the end of the dosing interval (Ctrough) derived from the 3rd injection IPK interval | Day 70 post injection at week 14 | 
| Percentage of Participants Meeting Serum Total Testosterone Average Concentration Criteria for Responder During the 4th Injection Interval in Part C | Responders were participants with serum total testosterone Cavg between 300 and 1000 ng/dL derived from the 4th injection IPK interval. | Days 0, 4, 7, 11, 42, and 70 post injection at week 24 | 
| Serum Total Testosterone Average Concentration During the 4th Injection Interval in Part C | Serum total testosterone Cavg derived from the 4th injection IPK interval | Days 0, 4, 7, 11, 42, and 70 post injection at week 24 | 
| Serum Total Testosterone Maximum Concentration During the 4th Injection Interval in Part C | Serum total testosterone Cmax derived from the 4th injection IPK interval | Days 0, 4, 7, 11, 42, and 70 post injection at week 24 | 
| Serum Total Testosterone Concentration at the End of the Dosing Interval Following the 4th Injection in Part C | Serum total testosterone Ctrough derived from the 4th injection IPK interval | Day 70 post injection at week 24 | 
| Percentage of Participants Meeting Serum Total Testosterone Maximum Concentration Criteria for Success During the 2nd Injection Interval in Part C2 | Success was defined as having ≥85% of participants with Cmax ≤1500 ng/dL, ≤5% of participants with Cmax 1800-2500 ng/dL, and no participants with Cmax >2500 ng/dL. | Days 0, 4, 7, 11, 14, and 70 post injection at week 4 | 
| Serum Total Testosterone Average Concentration During the 2nd Injection Interval in Part C2 | Serum total testosterone Cavg derived from the 2nd injection IPK interval | Days 0, 4, 7, 11, 14, and 70 post injection at week 4 | 
| Serum Total Testosterone Maximum Concentration During the 2nd Injection Interval in Part C2 | Serum total testosterone Cmax derived from the 2nd injection IPK interval | Days 0, 4, 7, 11, 14, and 70 post injection at week 4 | 
| Serum Total Testosterone at the End of the Dosing Interval Following the 2nd Injection in Part C2 | Serum total testosterone Ctrough derived from the 2nd injection IPK interval | Day 70 post injection at week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Total Testosterone Maximum Concentration in Part A |  | Days 0, 4, 7, 11, 14, 21, 28, 42, 56, 70, and 84 post injection at week 1, week 12, week 24, and week 36; and post injection at weeks 48, 60, 72, 84, 96, 108, and 120 | 
| Serum Total Testosterone Maximum Concentration in Part B |  | Post injection at week 1; post injection at week 8; days 0, 4, 7, 11, 14, 21, 28, 42, 56, 70, and 84 post injection at week 20; and post injection at weeks 32, 44, 56, 68, and 80 | 
| Percentage of Participants Meeting Serum Total Testosterone Maximum Concentration Criteria for Success During the 3rd Injection Interval in Part C | Success is defined as having ≥85% of participants with Cmax ≤1500 ng/dL, ≤5% of participants with Cmax 1800-2500 ng/dL, and no participants with Cmax >2500 ng/dL. | Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14 | 
| Percentage of Participants With at Least 1 Serum Total Testosterone Level <300 ng/dL at Any Time During the 3rd Injection Interval in Part C |  | Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14 | 
| Percentage of Participants With Serum Total Testosterone Average Concentration ≥300 ng/dL During the 3rd Injection Interval in Part C |  | Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14 | 
| Time to First Serum Total Testosterone Concentration <300 ng/dL Following the 3rd Injection Interval in Part C |  | Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14 | 
| Percentage of Participants With Clinical Success During the 3rd Injection Interval in Part C | Clinical success is defined as having both Cavg and Ctrough between 300 and 1000 ng/dL | Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14 | 
| Percentage of Participants With Serum Total Testosterone Maximum Concentration ≤1500, >1500 to <1800, 1800 to 2500, and >2500 ng/dL During the 3rd Injection Interval in Part C |  | Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14 | 
| Percentage of Participants Meeting Serum Total Testosterone Maximum Concentration Criteria for Success During the 4th Injection Interval in Part C | Success is defined as having ≥85% of participants with Cmax ≤1500 ng/dL, ≤5% of participants with Cmax 1800-2500 ng/dL, and no participants with Cmax >2500 ng/dL. | Days 0, 4, 7, 11, 42, and 70 post injection at week 24 | 
| Percentage of Participants With at Least 1 Serum Total Testosterone Level <300 ng/dL at Any Time During the 4th Injection Interval in Part C |  | Days 0, 4, 7, 11, 42, and 70 post injection at week 24 | 
| Percentage of Participants With Average Serum Total Testosterone Concentration ≥300 ng/dL During the 4th Injection Interval in Part C |  | Days 0, 4, 7, 11, 42, and 70 post injection at week 24 | 
| Time to First Serum Total Testosterone Concentration <300 ng/dL Following the 4th Injection Interval in Part C |  | Days 0, 4, 7, 11, 42, and 70 post injection at week 24 | 
| Percentage of Participants With Clinical Success During the 4th Injection Interval in Part C | Clinical success is defined as having both Cavg and Ctrough between 300 and 1000 ng/dL | Days 0, 4, 7, 11, 42, and 70 post injection at week 24 | 
| Percentage of Participants With Serum Total Testosterone Maximum Concentration ≤1500, >1500 to <1800, 1800 to 2500, and >2500 ng/dL During the 4th Injection Interval in Part C |  | Days 0, 4, 7, 11, 42, and 70 post injection at week 24 | 
| Percentage of Participants by Collapsed Category for Each Parameter of the Male Patient Global Assessment (M-PGA) at Day 21 of the 3rd Injection Interval in Part C | M-PGA is a 5-item self-report questionnaire to assess perception of change from pretreatment or baseline in hypogonadal symptoms including confidence/self-esteem, sexual performance, moods/behavior, overall feeling of well-being, and satisfaction with study treatment rated on a 7-point scale where items 1-4 were rated as 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7 (very much worse) and item 5 was rated as 1 (very much satisfied), 2 (much satisfied), 3 (minimally satisfied), 4 (neither satisfied nor dissatisfied), 5 (minimally dissatisfied), 6 (much dissatisfied), 7 (very much dissatisfied). Collapsed ratings: Improved=Very much, much, or minimally improved; Worsened=Very much, much, or minimally worse; No change; Satisfied=Very much, much, or minimally satisfied; Not satisfied=Very much, much, or minimally dissatisfied; No opinion (neither satisfied nor dissatisfied). | Day 21 post injection at week 14 | 
| Change in Body Mass Index From Baseline to Week 24 in Part C | Difference in Body Mass Index (BMI) from baseline to week 24 calculated from weight (kg) divided by height squared (m2) | Baseline, Week 24 | 
| Change in Weight From Baseline to Week 24 in Part C |  | Baseline, Week 24 | 
| Percentage of Participants With at Least 1 Serum Total Testosterone Concentration >1000, >1100, >1250, and <300 or >1000 ng/dL During the 2nd Injection Interval in Part C2 |  | Days 0, 4, 7, 11, 14, and 70 post injection at week 4 | 
| Serum Dihydrotestosterone Concentrations During the 2nd Injection Interval in Part C2 |  | Days 0, 4, 7, 11, 14, and 70 post injection at week 4 | 
| Serum Total Testosterone Concentrations in Part C2 |  | Screening; day 0; days 0, 4, 7, 11, and 14 post injection at week 4; weeks 14, 24, 34, and 44 | 
| Percentage of Participants With Serum Total Testosterone Concentrations Outside the Normal Range in Part C2 | Serum total testosterone concentrations outside the normal range are categorized as <300 ng/dL (below lower limit of normal range) and >1000 ng/dL (above upper limit of normal range) | Screening; day 0; days 0, 4, 7, 11, and 14 post injection at week 4; weeks 14, 24, 34, and 44 | 
| Trough Assessments of Serum Total Testosterone Concentrations in Part C2 |  | Screening; day 0; and weeks 4, 14, 24, 34, and 44 | 
| Serum Total Testosterone Maximum Concentration in Part C2 |  | Screening; day 0; days 0, 4, 7, 11, and 14 post injection at week 4; and weeks 14, 24, 34, and 44 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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investigational, testosterone, testosterone undecanoate, TU, Hypogonadism, primary hypogonadism, secondary hypogonadism