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

• Sponsor: Endo Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00467870
• Collaborator: (none)
• Enrollment: 531
• Location: 1
• Arms: 2
• Duration (Months): 40
• Patients Per Site Per Month: 13.3

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hypogonadism; Primary Hypogonadism; Secondary Hypogonadism	Drug: Testosterone Undecanoate 750 mg; Drug: Testosterone Undecanoate 1000 mg	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 531 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 750 mg dose of testosterone undecanoate	Drug: Testosterone Undecanoate 750 mg
Experimental: 2 1000 mg dose testosterone undecanoate	Drug: Testosterone Undecanoate 1000 mg

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Meeting Serum Total Testosterone Average Concentration Criteria for Responder 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]

   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.

2. Serum Total Testosterone Average Concentration 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]

   Serum total testosterone Cavg derived from the 3rd injection IPK interval

3. Serum Total Testosterone Maximum Concentration 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]

   Serum total testosterone maximum concentration (Cmax) derived from the 3rd injection IPK interval

4. Serum Total Testosterone Concentration at the End of the Dosing Interval Following the 3rd Injection in Part C [Day 70 post injection at week 14]

   Serum total testosterone concentration at the end of the dosing interval (Ctrough) derived from the 3rd injection IPK interval

5. Percentage of Participants Meeting Serum Total Testosterone Average Concentration Criteria for Responder During the 4th Injection Interval in Part C [Days 0, 4, 7, 11, 42, and 70 post injection at week 24]

   Responders were participants with serum total testosterone Cavg between 300 and 1000 ng/dL derived from the 4th injection IPK interval.

6. Serum Total Testosterone Average Concentration During the 4th Injection Interval in Part C [Days 0, 4, 7, 11, 42, and 70 post injection at week 24]

   Serum total testosterone Cavg derived from the 4th injection IPK interval

7. Serum Total Testosterone Maximum Concentration During the 4th Injection Interval in Part C [Days 0, 4, 7, 11, 42, and 70 post injection at week 24]

   Serum total testosterone Cmax derived from the 4th injection IPK interval

8. Serum Total Testosterone Concentration at the End of the Dosing Interval Following the 4th Injection in Part C [Day 70 post injection at week 24]

   Serum total testosterone Ctrough derived from the 4th injection IPK interval

9. Percentage of Participants Meeting Serum Total Testosterone Maximum Concentration Criteria for Success During the 2nd Injection Interval in Part C2 [Days 0, 4, 7, 11, 14, and 70 post injection at week 4]

   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.

10. Serum Total Testosterone Average Concentration During the 2nd Injection Interval in Part C2 [Days 0, 4, 7, 11, 14, and 70 post injection at week 4]

    Serum total testosterone Cavg derived from the 2nd injection IPK interval

11. Serum Total Testosterone Maximum Concentration During the 2nd Injection Interval in Part C2 [Days 0, 4, 7, 11, 14, and 70 post injection at week 4]

    Serum total testosterone Cmax derived from the 2nd injection IPK interval

12. Serum Total Testosterone at the End of the Dosing Interval Following the 2nd Injection in Part C2 [Day 70 post injection at week 4]

    Serum total testosterone Ctrough derived from the 2nd injection IPK interval

Secondary Outcome Measures

1. 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]

2. 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]

3. Percentage of Participants Meeting Serum Total Testosterone Maximum Concentration Criteria for Success 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]

   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.

4. 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]

5. 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]

6. 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]

7. Percentage of Participants With Clinical Success 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]

   Clinical success is defined as having both Cavg and Ctrough between 300 and 1000 ng/dL

8. 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]

9. Percentage of Participants Meeting Serum Total Testosterone Maximum Concentration Criteria for Success During the 4th Injection Interval in Part C [Days 0, 4, 7, 11, 42, and 70 post injection at week 24]

   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.

10. 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]

11. 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]

12. 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]

13. Percentage of Participants With Clinical Success During the 4th Injection Interval in Part C [Days 0, 4, 7, 11, 42, and 70 post injection at week 24]

    Clinical success is defined as having both Cavg and Ctrough between 300 and 1000 ng/dL

14. 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]

15. 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 [Day 21 post injection at week 14]

    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).

16. Change in Body Mass Index From Baseline to Week 24 in Part C [Baseline, Week 24]

    Difference in Body Mass Index (BMI) from baseline to week 24 calculated from weight (kg) divided by height squared (m2)

17. Change in Weight From Baseline to Week 24 in Part C [Baseline, Week 24]

18. 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]

19. Serum Dihydrotestosterone Concentrations During the 2nd Injection Interval in Part C2 [Days 0, 4, 7, 11, 14, and 70 post injection at week 4]

20. 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]

21. Percentage of Participants With Serum Total Testosterone Concentrations Outside the Normal Range in Part C2 [Screening; day 0; days 0, 4, 7, 11, and 14 post injection at week 4; weeks 14, 24, 34, and 44]

    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)

22. Trough Assessments of Serum Total Testosterone Concentrations in Part C2 [Screening; day 0; and weeks 4, 14, 24, 34, and 44]

23. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indevus Pharmaceuticals, Inc.	Lexington	Massachusetts	United States	02421

Sponsors and Collaborators

• Endo Pharmaceuticals

Investigators

• Study Director: Indevus Pharmaceuticals, Inc., Sponsor GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Endo Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00467870
• Other Study ID Numbers: IP157-001
• First Posted: May 1, 2007
• Last Update Posted: Oct 5, 2017
• Last Verified: Sep 1, 2017

• Keywords provided by Endo Pharmaceuticals: investigational; testosterone; testosterone undecanoate; TU; Hypogonadism; primary hypogonadism; secondary hypogonadism
• Additional relevant MeSH terms: Hypogonadism; Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate

Study Results

Participant Flow

Pre-assignment Detail	Of 531 subjects who were enrolled, 524 subjects received study treatment (at least 1 injection). The 7 enrolled subjects who did not receive treatment (2 in Part A and 5 in Part C) were excluded from all analyses.

Arm/Group Title	A-TU 750 mg	A-TU 1000 mg	B-TU 750 mg	B-TU 1000 mg	C-TU 750 mg	C2-TU 750 mg
Arm/Group Description	750 mg testosterone undecanoate (TU) in 3 mL oily solution, intramuscularly (IM) every 12 weeks for up to 3 years in Part A	1000 mg TU in 4 mL oily solution, IM every 12 weeks for up to 3 years in Part A	1000 mg TU in 4 mL oily solution, IM at baseline, and then 750 mg TU in 3 mL oily solution at week 8 and again every 10 weeks for up to 23 months in Part B	1000 mg TU in 4 mL oily solution, IM at baseline, week 8, and then every 12 weeks for up to 24 months in Part B	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 12 months in Part C2
Period Title: Overall Study
STARTED	120	117	22	112	130	23
COMPLETED	75	74	18	79	93	21
NOT COMPLETED	45	43	4	33	37	2

Baseline Characteristics

Arm/Group Title	A-TU 750 mg	A-TU 1000 mg	B-TU 750 mg	B-TU 1000 mg	C-TU 750 mg	C2-TU 750 mg	Total
Arm/Group Description	750 mg TU in 3 mL oily solution, IM every 12 weeks for up to 3 years in Part A	1000 mg TU in 4 mL oily solution, IM every 12 weeks for up to 3 years in Part A	1000 mg TU in 4 mL oily solution, IM at baseline, and then 750 mg TU in 3 mL oily solution at week 8 and again every 10 weeks for up to 23 months in Part B	1000 mg TU in 4 mL oily solution, IM at baseline, week 8, and then every 12 weeks for up to 24 months in Part B	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 12 months in Part C2	Total of all reporting groups
Overall Participants	120	117	22	112	130	23	524
Age, Customized (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.0 (10.64)	55.9 (10.77)	55.3 (10.40)	52.9 (10.96)	54.2 (10.25)	54.5 (10.63)	54.4 (10.56)
Sex/Gender, Customized (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	120 100%	117 100%	22 100%	112 100%	130 100%	23 100%	524 100%
Race/Ethnicity, Customized (participants) [Number]
White	101 84.2%	106 90.6%	18 81.8%	92 82.1%	97 74.6%	18 78.3%	432 82.4%
Asian	2 1.7%	0 0%	1 4.5%	1 0.9%	0 0%	0 0%	4 0.8%
Black	11 9.2%	8 6.8%	1 4.5%	15 13.4%	16 12.3%	4 17.4%	55 10.5%
Hispanic	3 2.5%	3 2.6%	2 9.1%	4 3.6%	14 10.8%	1 4.3%	27 5.2%
Other	3 2.5%	0 0%	0 0%	0 0%	3 2.3%	0 0%	6 1.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Meeting Serum Total Testosterone Average Concentration Criteria for Responder During the 3rd Injection Interval in Part C
Description	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.
Time Frame	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	117
Number (95% Confidence Interval) [percentage of participants]	94.0 78.3%

2. Primary Outcome

Title	Serum Total Testosterone Average Concentration During the 3rd Injection Interval in Part C
Description	Serum total testosterone Cavg derived from the 3rd injection IPK interval
Time Frame	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14

Outcome Measure Data

Analysis Population Description

PK population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	117
Mean (Standard Deviation) [ng/dL]	494.9373 (141.46351)

3. Primary Outcome

Title	Serum Total Testosterone Maximum Concentration During the 3rd Injection Interval in Part C
Description	Serum total testosterone maximum concentration (Cmax) derived from the 3rd injection IPK interval
Time Frame	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14

Outcome Measure Data

Analysis Population Description

PK population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	117
Mean (Standard Deviation) [ng/dL]	890.583 (345.1148)

4. Primary Outcome

Title	Serum Total Testosterone Concentration at the End of the Dosing Interval Following the 3rd Injection in Part C
Description	Serum total testosterone concentration at the end of the dosing interval (Ctrough) derived from the 3rd injection IPK interval
Time Frame	Day 70 post injection at week 14

Outcome Measure Data

Analysis Population Description

PK population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	117
Mean (Standard Deviation) [ng/dL]	323.522 (99.1081)

5. Primary Outcome

Title	Percentage of Participants Meeting Serum Total Testosterone Average Concentration Criteria for Responder During the 4th Injection Interval in Part C
Description	Responders were participants with serum total testosterone Cavg between 300 and 1000 ng/dL derived from the 4th injection IPK interval.
Time Frame	Days 0, 4, 7, 11, 42, and 70 post injection at week 24

Outcome Measure Data

Analysis Population Description

Steady-state PK population includes all participants in the PK population with non-missing 4th and 5th injection serum total testosterone concentrations (26 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	104
Number (95% Confidence Interval) [percentage of participants]	96.2 80.2%

6. Primary Outcome

Title	Serum Total Testosterone Average Concentration During the 4th Injection Interval in Part C
Description	Serum total testosterone Cavg derived from the 4th injection IPK interval
Time Frame	Days 0, 4, 7, 11, 42, and 70 post injection at week 24

Outcome Measure Data

Analysis Population Description

Steady-state PK population includes all participants in the PK population with non-missing 4th and 5th injection serum total testosterone concentrations (26 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	104
Mean (Standard Deviation) [ng/dL]	514.2792 (163.11476)

7. Primary Outcome

Title	Serum Total Testosterone Maximum Concentration During the 4th Injection Interval in Part C
Description	Serum total testosterone Cmax derived from the 4th injection IPK interval
Time Frame	Days 0, 4, 7, 11, 42, and 70 post injection at week 24

Outcome Measure Data

Analysis Population Description

Steady-state PK population includes all participants in the PK population with non-missing 4th and 5th injection serum total testosterone concentrations (26 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	104
Mean (Standard Deviation) [ng/dL]	837.648 (412.0692)

8. Primary Outcome

Title	Serum Total Testosterone Concentration at the End of the Dosing Interval Following the 4th Injection in Part C
Description	Serum total testosterone Ctrough derived from the 4th injection IPK interval
Time Frame	Day 70 post injection at week 24

Outcome Measure Data

Analysis Population Description

Steady-state PK population includes all participants in the PK population with non-missing 4th and 5th injection serum total testosterone concentrations (26 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	104
Mean (Standard Deviation) [ng/dL]	342.800 (106.9180)

9. Primary Outcome

Title	Percentage of Participants Meeting Serum Total Testosterone Maximum Concentration Criteria for Success During the 2nd Injection Interval in Part C2
Description	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.
Time Frame	Days 0, 4, 7, 11, 14, and 70 post injection at week 4

Outcome Measure Data

Analysis Population Description

Total patient sample/PK sample includes participants who were enrolled, received injection 2, and had at least 1 post-injection 2 IPK sample (no participants were excluded)

Arm/Group Title	C2-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 12 months in Part C2
Measure Participants	23
Cmax ≤1500 ng/dL	95.7 79.8%
Cmax 1800-2500 ng/dL	0 0%
Cmax >2500 ng/dL	0 0%

10. Primary Outcome

Title	Serum Total Testosterone Average Concentration During the 2nd Injection Interval in Part C2
Description	Serum total testosterone Cavg derived from the 2nd injection IPK interval
Time Frame	Days 0, 4, 7, 11, 14, and 70 post injection at week 4

Outcome Measure Data

Analysis Population Description

Total patient sample/PK sample includes participants who were enrolled, received injection 2, and had at least 1 post-injection 2 IPK sample (no participants were excluded)

Arm/Group Title	C2-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 12 months in Part C2
Measure Participants	23
Mean (Standard Deviation) [ng/dL]	449.6455 (157.00582)

11. Primary Outcome

Title	Serum Total Testosterone Maximum Concentration During the 2nd Injection Interval in Part C2
Description	Serum total testosterone Cmax derived from the 2nd injection IPK interval
Time Frame	Days 0, 4, 7, 11, 14, and 70 post injection at week 4

Outcome Measure Data

Analysis Population Description

Total patient sample/PK sample includes participants who were enrolled, received injection 2, and had at least 1 post-injection 2 IPK sample (no participants were excluded)

Arm/Group Title	C2-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 12 months in Part C2
Measure Participants	23
Mean (Standard Deviation) [ng/dL]	689.002 (266.9442)

12. Primary Outcome

Title	Serum Total Testosterone at the End of the Dosing Interval Following the 2nd Injection in Part C2
Description	Serum total testosterone Ctrough derived from the 2nd injection IPK interval
Time Frame	Day 70 post injection at week 4

Outcome Measure Data

Analysis Population Description

Total patient sample/PK sample includes participants who were enrolled, received injection 2, and had at least 1 post-injection 2 IPK sample (no participants were excluded)

Arm/Group Title	C2-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 12 months in Part C2
Measure Participants	23
Mean (Standard Deviation) [ng/dL]	317.419 (105.3124)

13. Secondary Outcome

Title	Serum Total Testosterone Maximum Concentration in Part A
Time Frame	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

Outcome Measure Data

Analysis Population Description

Total patient sample includes participants who were enrolled and received at least 1 injection; participants without any IPK sample collections were excluded from this analysis (20 from A-TU 750 mg and 11 from A-TU 1000 mg)

Arm/Group Title	A-TU 750 mg	A-TU 1000 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM every 12 weeks for up to 3 years in Part A	1000 mg TU in 4 mL oily solution, IM every 12 weeks for up to 3 years in Part A
Measure Participants	106	100
Mean (Standard Deviation) [ng/dL]	805.867 (308.5417)	1023.591 (394.3051)

14. Secondary Outcome

Title	Serum Total Testosterone Maximum Concentration in Part B
Time Frame	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

Outcome Measure Data

Analysis Population Description

Total patient sample includes participants who were enrolled and received at least 1 injection; participants without any IPK sample collections were excluded from this analysis (2 from B-TU 750 mg and 12 from B-TU 1000 mg)

Arm/Group Title	B-TU 750 mg	B-TU 1000 mg
Arm/Group Description	1000 mg TU in 4 mL oily solution, IM at baseline, and then 750 mg TU in 3 mL oily solution at week 8 and again every 10 weeks for up to 23 months in Part B	1000 mg TU in 4 mL oily solution, IM at baseline, week 8, and then every 12 weeks for up to 24 months in Part B
Measure Participants	20	100
Mean (Standard Deviation) [ng/dL]	986.364 (330.4247)	1047.739 (571.1648)

15. Secondary Outcome

Title	Percentage of Participants Meeting Serum Total Testosterone Maximum Concentration Criteria for Success During the 3rd Injection Interval in Part C
Description	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.
Time Frame	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14

Outcome Measure Data

Analysis Population Description

PK population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	117
Cmax ≤1500 ng/dL	92.3 76.9%
Cmax 1800-2500 ng/dL	0 0%
Cmax >2500 ng/dL	0 0%

16. Secondary Outcome

Title	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
Time Frame	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14

Outcome Measure Data

Analysis Population Description

PK population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	117
Number (95% Confidence Interval) [percentage of participants]	51.3 42.8%

17. Secondary Outcome

Title	Percentage of Participants With Serum Total Testosterone Average Concentration ≥300 ng/dL During the 3rd Injection Interval in Part C
Time Frame	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14

Outcome Measure Data

Analysis Population Description

PK population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	117
Number (95% Confidence Interval) [percentage of participants]	94.9 79.1%

18. Secondary Outcome

Title	Time to First Serum Total Testosterone Concentration <300 ng/dL Following the 3rd Injection Interval in Part C
Time Frame	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14

Outcome Measure Data

Analysis Population Description

PK population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis); an additional 57 participants who did not have serum total testosterone concentrations <300 ng/dL were also excluded from analysis

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	60
Mean (Standard Deviation) [days]	50.2 (17.41)

19. Secondary Outcome

Title	Percentage of Participants With Clinical Success During the 3rd Injection Interval in Part C
Description	Clinical success is defined as having both Cavg and Ctrough between 300 and 1000 ng/dL
Time Frame	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14

Outcome Measure Data

Analysis Population Description

PK population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	117
Number (95% Confidence Interval) [percentage of participants]	53.8 44.8%

20. Secondary Outcome

Title	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
Time Frame	Days 0, 4, 7, 11, 14, 21, 28, 42, 56, and 70 post injection at week 14

Outcome Measure Data

Analysis Population Description

PK population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	117
Cmax ≤1500 ng/dL	92.3 76.9%
Cmax >1500-<1800 ng/dL	7.7 6.4%
Cmax 1800-2500 ng/dL	0 0%
Cmax >2500 ng/dL	0 0%

21. Secondary Outcome

Title	Percentage of Participants Meeting Serum Total Testosterone Maximum Concentration Criteria for Success During the 4th Injection Interval in Part C
Description	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.
Time Frame	Days 0, 4, 7, 11, 42, and 70 post injection at week 24

Outcome Measure Data

Analysis Population Description

Steady-state PK population includes all participants in the PK population with non-missing 4th and 5th injection serum total testosterone concentrations (26 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	104
Cmax ≤1500 ng/dL	92.3 76.9%
Cmax 1800-2500 ng/dL	3.8 3.2%
Cmax >2500 ng/dL	0 0%

22. Secondary Outcome

Title	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
Time Frame	Days 0, 4, 7, 11, 42, and 70 post injection at week 24

Outcome Measure Data

Analysis Population Description

Steady-state PK population includes all participants in the PK population with non-missing 4th and 5th injection serum total testosterone concentrations (26 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	104
Number (95% Confidence Interval) [percentage of participants]	37.5 31.3%

23. Secondary Outcome

Title	Percentage of Participants With Average Serum Total Testosterone Concentration ≥300 ng/dL During the 4th Injection Interval in Part C
Time Frame	Days 0, 4, 7, 11, 42, and 70 post injection at week 24

Outcome Measure Data

Analysis Population Description

Steady-state PK population includes all participants in the PK population with non-missing 4th and 5th injection serum total testosterone concentrations (26 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	104
Number (95% Confidence Interval) [percentage of participants]	96.2 80.2%

24. Secondary Outcome

Title	Time to First Serum Total Testosterone Concentration <300 ng/dL Following the 4th Injection Interval in Part C
Time Frame	Days 0, 4, 7, 11, 42, and 70 post injection at week 24

Outcome Measure Data

Analysis Population Description

Steady-state PK population includes all participants in the PK population with non-missing 4th and 5th injection serum total testosterone concentrations (26 participants were excluded from analysis); an additional 57 participants who did not have serum total testosterone concentrations <300 ng/dL were also excluded from analysis

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	39
Mean (Standard Deviation) [days]	60.6 (17.51)

25. Secondary Outcome

Title	Percentage of Participants With Clinical Success During the 4th Injection Interval in Part C
Description	Clinical success is defined as having both Cavg and Ctrough between 300 and 1000 ng/dL
Time Frame	Days 0, 4, 7, 11, 42, and 70 post injection at week 24

Outcome Measure Data

Analysis Population Description

Steady-state PK population includes all participants in the PK population with non-missing 4th and 5th injection serum total testosterone concentrations (26 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	104
Number (95% Confidence Interval) [percentage of participants]	62.5 52.1%

26. Secondary Outcome

Title	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
Time Frame	Days 0, 4, 7, 11, 42, and 70 post injection at week 24

Outcome Measure Data

Analysis Population Description

Steady-state PK population includes all participants in the PK population with non-missing 4th and 5th injection serum total testosterone concentrations (26 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	104
Cmax ≤1500 ng/dL	92.3 76.9%
Cmax >1500 to <1800 ng/dL	3.8 3.2%
Cmax 1800 to 2500 ng/dL	3.8 3.2%
Cmax >2500 ng/dL	0 0%

27. Secondary Outcome

Title	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
Description	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).
Time Frame	Day 21 post injection at week 14

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis)

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	117
Confidence or Self-Esteem Improved	82.6 68.8%
Confidence or Self-Esteem No Change	17.4 14.5%
Confidence or Self-Esteem Worsened	0 0%
Satisfaction with Sexual Performance Improved	80.0 66.7%
Satisfaction with Sexual Performance No Change	17.4 14.5%
Satisfaction with Sexual Performance Worsened	2.6 2.2%
General Moods and Behavoir Improved	80.9 67.4%
General Moods and Behavoir No Change	19.1 15.9%
General Moods and Behavoir Worsened	0 0%
Overal Feeling of Well-Being Improved	81.7 68.1%
Overal Feeling of Well-Being No Change	18.3 15.3%
Overal Feeling of Well-Being Worsened	0 0%
Satisfaction with Study Treatment Satisfied	92.2 76.8%
Satisfaction with Study Treatment No Opinion	7.8 6.5%
Satisfaction with Study Treatment Not Satisfied	0 0%

28. Secondary Outcome

Title	Change in Body Mass Index From Baseline to Week 24 in Part C
Description	Difference in Body Mass Index (BMI) from baseline to week 24 calculated from weight (kg) divided by height squared (m2)
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

PK population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis); 1 additional participant did not have a measurement at week 24 and was also excluded from analysis

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	116
Mean (Standard Deviation) [kg/m2]	0.023 (0.9543)

29. Secondary Outcome

Title	Change in Weight From Baseline to Week 24 in Part C
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

PK population includes participants who had a minimum of 4 serum total testosterone concentration values within the 3rd injection interval (13 participants were excluded from analysis); 1 additional participant did not have a measurement at week 24 and was also excluded from analysis

Arm/Group Title	C-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 20 months in Part C
Measure Participants	116
Mean (Standard Deviation) [kg]	0.06 (3.009)

30. Secondary Outcome

Title	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
Time Frame	Days 0, 4, 7, 11, 14, and 70 post injection at week 4

Outcome Measure Data

Analysis Population Description

Total patient sample/PK sample includes participants who were enrolled, received injection 2, and had at least 1 post-injection 2 IPK sample (no participants were excluded)

Arm/Group Title	C2-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 12 months in Part C2
Measure Participants	23
Cmax >1000 ng/dL	8.7 7.3%
Cmax >1100 ng/dL	4.3 3.6%
Cmax >1250 ng/dL	4.3 3.6%
Cmax <300 or >1000 ng/dL	60.9 50.8%

31. Secondary Outcome

Title	Serum Dihydrotestosterone Concentrations During the 2nd Injection Interval in Part C2
Time Frame	Days 0, 4, 7, 11, 14, and 70 post injection at week 4

Outcome Measure Data

Analysis Population Description

Total patient sample/PK sample includes participants who were enrolled, received injection 2, and had at least 1 post-injection 2 IPK sample (no participants were excluded)

Arm/Group Title	C2-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 12 months in Part C2
Measure Participants	23
Day 0 (n=23)	180.33 (111.646)
Day 4 (n=20)	301.85 (188.818)
Day 7 (n=22)	322.74 (197.018)
Day 11 (n=22)	332.92 (210.534)
Day 14 (n=21)	324.74 (191.489)
Day 70 (n=23)	230.71 (113.578)

32. Secondary Outcome

Title	Serum Total Testosterone Concentrations in Part C2
Time Frame	Screening; day 0; days 0, 4, 7, 11, and 14 post injection at week 4; weeks 14, 24, 34, and 44

Outcome Measure Data

Analysis Population Description

Total patient sample/PK sample includes participants who were enrolled, received injection 2, and had at least 1 post-injection 2 IPK sample (no participants were excluded)

Arm/Group Title	C2-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 12 months in Part C2
Measure Participants	23
Screening (n=22)	197.629 (75.8138)
Day 0 (n=23)	210.363 (81.6797)
Day 0 at Week 4 (n=23)	254.669 (112.7259)
Day 4 post injection at Week 4 (n=20)	578.419 (304.6675)
Day 7 post injection at Week 4 (n=22)	606.484 (266.4847)
Day 11 post injection at Week 4 (n=22)	580.614 (244.3727)
Day 14 post injection at week 4 (n=21)	545.236 (234.5882)
Week 14 (n=23)	317.419 (105.3124)
Week 24 (n=23)	316.215 (126.1430)
Week 34 (n=22)	374.698 (161.7627)
Week 44 (n=20)	375.797 (136.5283)

33. Secondary Outcome

Title	Percentage of Participants With Serum Total Testosterone Concentrations Outside the Normal Range in Part C2
Description	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)
Time Frame	Screening; day 0; days 0, 4, 7, 11, and 14 post injection at week 4; weeks 14, 24, 34, and 44

Outcome Measure Data

Analysis Population Description

Total patient sample/PK sample includes participants who were enrolled, received injection 2, and had at least 1 post-injection 2 IPK sample (no participants were excluded)

Arm/Group Title	C2-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 12 months in Part C2
Measure Participants	23
Screening, <300 ng/dL	100.0 83.3%
Screening, >1000 ng/dL	0 0%
Day 0, <300 ng/dL	91.3 76.1%
Day 0, >1000 ng/dL	0 0%
Day 0 at Week 4, <300 ng/dL	78.3 65.3%
Day 0 at Week 4, >1000 ng/dL	0 0%
Day 4 post injection at Week 4, <300 ng/dL	15.0 12.5%
Day 4 post injection at Week 4, >1000 ng/dL	5.0 4.2%
Day 7 post injection at Week 4, <300 ng/dL	0 0%
Day 7 post injection at Week 4, >1000 ng/dL	9.1 7.6%
Day 11 post injection at Week 4, <300 ng/dL	0 0%
Day 11 post injection at Week 4, >1000 ng/dL	4.5 3.8%
Day 14 post injection at Week 4, <300 ng/dL	0 0%
Day 14 post injection at Week 4, >1000 ng/dL	4.8 4%
Week 14, <300 ng/dL	52.2 43.5%
Week 14, >1000 ng/dL	0 0%
Week 24, <300 ng/dL	47.8 39.8%
Week 24, >1000 ng/dL	0 0%
Week 34, <300 ng/dL	36.4 30.3%
Week 34, >1000 ng/dL	0 0%
Week 44, <300 ng/dL	35.0 29.2%
Week 44, >1000 ng/dL	0 0%

34. Secondary Outcome

Title	Trough Assessments of Serum Total Testosterone Concentrations in Part C2
Time Frame	Screening; day 0; and weeks 4, 14, 24, 34, and 44

Outcome Measure Data

Analysis Population Description

Total patient sample/PK sample includes participants who were enrolled, received injection 2, and had at least 1 post-injection 2 IPK sample (no participants were excluded)

Arm/Group Title	C2-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 12 months in Part C2
Measure Participants	23
Screening (n=22)	197.629 (75.8138)
Day 0 (n=23)	210.363 (81.6797)
Week 4 (n=23)	254.669 (112.7529)
Week 14 (n=23)	317.419 (105.3124)
Week 24 (n=23)	316.215 (126.1430)
Week 34 (n=22)	374.698 (161.7627)
Week 44 (n=20)	375.797 (136.5283)

35. Secondary Outcome

Title	Serum Total Testosterone Maximum Concentration in Part C2
Time Frame	Screening; day 0; days 0, 4, 7, 11, and 14 post injection at week 4; and weeks 14, 24, 34, and 44

Outcome Measure Data

Analysis Population Description

Total patient sample/PK sample includes participants who were enrolled, received injection 2, and had at least 1 post-injection 2 IPK sample (no participants were excluded)

Arm/Group Title	C2-TU 750 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline, week 4, and then every 10 weeks for up to 12 months in Part C2
Measure Participants	23
Mean (Standard Deviation) [ng/dL]	711.343 (257.5643)

Adverse Events

Time Frame	Throughout the study (up to 3 years)
Adverse Event Reporting Description	Includes all participants who were enrolled and received at least 1 injection, pooled into groups of maximum TU dose received at any time during the study
Arm/Group Title	TU 750 mg		TU 1000 mg
Arm/Group Description	750 mg TU in 3 mL oily solution, IM at baseline and during the study in Part A, C, or C2 (includes participants from A-750 mg, C-750 mg, and C2-750 mg)		1000 mg TU in 4 mL oily solution, IM at any time during the study in Part A or B (includes participants from A-1000 mg, B-750 mg, and B-1000 mg)
All Cause Mortality
	TU 750 mg		TU 1000 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	TU 750 mg		TU 1000 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/272 (14%)		37/252 (14.7%)
Cardiac disorders
Acute myocardial infarction	0/272 (0%)		1/252 (0.4%)
Arrhythmia	0/272 (0%)		1/252 (0.4%)
Arrhythmia superventricular	0/272 (0%)		1/252 (0.4%)
Atrial fibrillation	2/272 (0.7%)		1/252 (0.4%)
Cardiac arrest	1/272 (0.4%)		0/252 (0%)
Cardiac failure	0/272 (0%)		1/252 (0.4%)
Cardiac failure congestive	1/272 (0.4%)		1/252 (0.4%)
Coronary artery disease	1/272 (0.4%)		3/252 (1.2%)
Hypertrophic cardiomyopathy	0/272 (0%)		1/252 (0.4%)
Left ventricular dysfunction	1/272 (0.4%)		0/252 (0%)
Myocardial infarction	3/272 (1.1%)		2/252 (0.8%)
Ventricular tachycardia	0/272 (0%)		1/252 (0.4%)
Ear and labyrinth disorders
Tinnitus	1/272 (0.4%)		0/252 (0%)
Eye disorders
Cataract	0/272 (0%)		1/252 (0.4%)
Gastrointestinal disorders
Abdonimal discomfort	0/272 (0%)		1/252 (0.4%)
Abdominal hernia obstructive	1/272 (0.4%)		0/252 (0%)
Colitis Ischaemic	1/272 (0.4%)		0/252 (0%)
Diverticulum intestinal	1/272 (0.4%)		0/252 (0%)
Faecaloma	1/272 (0.4%)		0/252 (0%)
Gastric ulcer	1/272 (0.4%)		0/252 (0%)
Gastrointestinal haemorrhage	0/272 (0%)		1/252 (0.4%)
Pancreatitis acute	1/272 (0.4%)		0/252 (0%)
General disorders
Chest pain	1/272 (0.4%)		0/252 (0%)
Medical device complication	1/272 (0.4%)		0/252 (0%)
Non-cardiac chest pain	0/272 (0%)		2/252 (0.8%)
Infections and infestations
Arthritis bacterial	0/272 (0%)		1/252 (0.4%)
Bacteraemia	1/272 (0.4%)		0/252 (0%)
Device related infection	0/272 (0%)		1/252 (0.4%)
Diverticulitis	1/272 (0.4%)		0/252 (0%)
Enterococcal bacteraemia	0/272 (0%)		1/252 (0.4%)
Escherichia urinary tract infection	0/272 (0%)		1/252 (0.4%)
Pharyngitis streptococcal	1/272 (0.4%)		0/252 (0%)
Sepsis	1/272 (0.4%)		0/252 (0%)
Sinusitis	1/272 (0.4%)		0/252 (0%)
Urinary tract infection	1/272 (0.4%)		2/252 (0.8%)
Gastroenteritis viral	0/272 (0%)		1/252 (0.4%)
Injury, poisoning and procedural complications
Overdose	0/272 (0%)		1/252 (0.4%)
Post procedural swelling	0/272 (0%)		1/252 (0.4%)
Road traffic accident	0/272 (0%)		1/252 (0.4%)
Stab wound	1/272 (0.4%)		0/252 (0%)
Tendon rupture	0/272 (0%)		1/252 (0.4%)
Wound dehiscence	0/272 (0%)		1/252 (0.4%)
Wrist fracture	1/272 (0.4%)		0/252 (0%)
Musculoskeletal and connective tissue disorders
Arthritis	0/272 (0%)		2/252 (0.8%)
Cervical spinal stenosis	2/272 (0.7%)		1/252 (0.4%)
Intervertebral disc degeneration	0/272 (0%)		1/252 (0.4%)
Intervertebral disc disorder	2/272 (0.7%)		0/252 (0%)
Lumbar spinal stenosis	1/272 (0.4%)		0/252 (0%)
Osteoarthritis	1/272 (0.4%)		3/252 (1.2%)
Rotator cuff syndrome	0/272 (0%)		1/252 (0.4%)
Spinal column stenosis	3/272 (1.1%)		1/252 (0.4%)
Spinal ostheoarthritis	0/272 (0%)		1/252 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	4/272 (1.5%)		3/252 (1.2%)
Bladder cancer	1/272 (0.4%)		0/252 (0%)
Colon cancer	0/272 (0%)		1/252 (0.4%)
Hepatic neoplasm malignant	0/272 (0%)		1/252 (0.4%)
Lung cancer metastatic	0/272 (0%)		1/252 (0.4%)
Lung neoplasm malignant	0/272 (0%)		1/252 (0.4%)
Metastases to bone	0/272 (0%)		1/252 (0.4%)
Pancreatic carcinoma	0/272 (0%)		1/252 (0.4%)
Parathyroid tumour benign	1/272 (0.4%)		0/252 (0%)
Nervous system disorders
Cerebrovascular accident	1/272 (0.4%)		2/252 (0.8%)
Convulsion	0/272 (0%)		1/252 (0.4%)
Psychiatric disorders
Anxiety	1/272 (0.4%)		0/252 (0%)
Renal and urinary disorders
Nephrolithiasis	0/272 (0%)		1/252 (0.4%)
Renal artery stenosis	0/272 (0%)		1/252 (0.4%)
Renal failure acute	0/272 (0%)		1/252 (0.4%)
Reproductive system and breast disorders
Prostatitis	1/272 (0.4%)		3/252 (1.2%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/272 (0.4%)		0/252 (0%)
Pneumothorax	1/272 (0.4%)		0/252 (0%)
Surgical and medical procedures
Knee arthroplasty	0/272 (0%)		2/252 (0.8%)
Vascular disorders
Deep vein thrombosis	1/272 (0.4%)		0/252 (0%)
Peripheral arterial occlusive disease	0/272 (0%)		1/252 (0.4%)
Other (Not Including Serious) Adverse Events
	TU 750 mg		TU 1000 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	131/272 (48.2%)		120/252 (47.6%)
Gastrointestinal disorders
Diarrhoae	4/272 (1.5%)		11/252 (4.4%)
Nausea	4/272 (1.5%)		8/252 (3.2%)
General disorders
Fatigue	17/272 (6.3%)		8/252 (3.2%)
Injection site pain	10/272 (3.7%)		15/252 (6%)
Infections and infestations
Sinusitis	18/272 (6.6%)		13/252 (5.2%)
Upper respiratory tract infection	15/272 (5.5%)		15/252 (6%)
Nasopharyngitis	14/272 (5.1%)		14/252 (5.6%)
Bronchitis	12/272 (4.4%)		8/252 (3.2%)
Urinary tract infection	5/272 (1.8%)		9/252 (3.6%)
Investigations
Prostatic specific antigen increased	20/272 (7.4%)		10/252 (4%)
Musculoskeletal and connective tissue disorders
Arthralgia	12/272 (4.4%)		11/252 (4.4%)
Back Pain	13/272 (4.8%)		10/252 (4%)
Musculoskelatal pain	6/272 (2.2%)		12/252 (4.8%)
Pain in extremity	9/272 (3.3%)		9/252 (3.6%)
Nervous system disorders
Headache	6/272 (2.2%)		8/252 (3.2%)
Psychiatric disorders
Insomnia	12/272 (4.4%)		12/252 (4.8%)
Depression	8/272 (2.9%)		8/252 (3.2%)
Anxiety	5/272 (1.8%)		8/252 (3.2%)
Renal and urinary disorders
Dysuria	3/272 (1.1%)		8/252 (3.2%)
Reproductive system and breast disorders
Prostatitis	15/272 (5.5%)		13/252 (5.2%)
Erectile dysfunction	4/272 (1.5%)		10/252 (4%)
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome	10/272 (3.7%)		4/252 (1.6%)
Skin and subcutaneous tissue disorders
Acne	9/272 (3.3%)		4/252 (1.6%)
Vascular disorders
Hypertension	16/272 (5.9%)		10/252 (4%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.