CCN007: Study of the Safety, and Sperm and Gonadotropin Suppression of a Contraceptive Gel in Normal Men

• Sponsor: Health Decisions (Other)
• Overall Status: Completed
• CT.gov ID: NCT00891228
• Collaborator: Population Council (Other), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 99
• Locations: 2
• Arms: 3
• Duration (Months): 30
• Patients Per Site: 49.5
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

To determine the number of men who have suppression of sperm production when using a daily regimen of Nestorone® Gel (0, 8 or 12 mg) and Testosterone Gel applied transdermally.

Condition or Disease	Intervention/Treatment	Phase
Contraception	Drug: Testosterone; Drug: Nestorone®; Drug: Nestorone®; Drug: Nestorone®	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 99 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Multicenter, Randomized, Double-Blind Comparator Trial of the Safety and Sperm and Gonadotropin Suppression Resulting From Combined Use of Nestorone® Gel (0, 8 or 12 mg NES) and Testosterone Gel (10 g) Compared With Testosterone Gel in Normal Men
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Testosterone Gel 10 g and Nestorone® 0 mg per day Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head.	Drug: Testosterone; Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily.; Drug: Nestorone®; Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head.
Experimental: Testosterone Gel 10 g and Nestorone® 8 mg per day Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg NES mL gel) by pressing two times with 2 mL dispenser head.	Drug: Testosterone; Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily.; Drug: Nestorone®; Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg Nestorone® mL gel) by pressing two times with 2 mL dispenser head.
Experimental: Testosterone Gel 10 g plus Nestorone® Gel 12 mg per day Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head.	Drug: Testosterone; Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily.; Drug: Nestorone®; Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head.

Outcome Measures

Primary Outcome Measures

1. The Number of Men Who Have Suppression of Sperm Production ≤1Million/mL Million/mL When Using a Daily Regimen of Nestorone® Gel (0, 8 or 12 mg) and Testosterone Gel Applied Transdermally. [24 Weeks]

Secondary Outcome Measures

1. The Number of Men Who Have Suppression of Sperm Production ≤3 Million/mL ≤ 3 Million/mL or Azoospermia When Using a Daily Regimen of Nestorone® Gel (0, 8 or 12 mg) and Testosterone Gel. [24 Weeks]

2. The Number of Men Who Have Azoospermia [24 Weeks]

3. The Impact on Sperm Motility in Men Who Are Not Azoospermic Azoospermic. [24 Weeks]

4. The Impact on Sperm Morphology in Men Who Are Not Azoospermic [24 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria

Men who meet all the following criteria are eligible for enrollment in the trial:

1. Male volunteers in good health as confirmed by physical examination, medical history, and clinical laboratory tests of blood and urine at the time of screening

2. 18 to 50 years of age

3. BMI ≤ 33 calculated as weight in Kg/ (height in cm) 2

4. No history of hormonal therapy use in the last six months prior to the first screening visit

5. Subject will agree to use a recognized effective method of contraception with his partner (i.e. at a minimum, use double-barrier contraception) during the course of the study treatment and recovery phase

6. In the opinion of the investigator, subject is able to comply with the protocol, understand and sign an informed consent and HIPAA form

7. Does not meet any of the exclusion criteria.

Exclusion Criteria:

Men who meet any of the following criteria are NOT eligible for enrollment in the trial:

1. Men participating in another clinical trial involving an investigational drug within the last 30 days prior to the first screening visit

2. Men not living in the catchment's area of the clinic or within a reasonable distance from the site

3. Clinically significant abnormal findings at screening

4. Elevated PSA (levels ≥ 4 ng/mL), according to local laboratory normal values

5. Abnormal serum chemistry values, according to local laboratory normal values that indicate liver or kidney dysfunction or that may be considered clinically significant. Other abnormal lab values may also be exclusionary, at the discretion of the investigator

6. Sperm concentration below 15 million/mL in more than one of three screening samples

7. Use of androgens or body building substances within 6 months before first screening visit

8. Diastolic (D) blood pressure (BP) ≥ 85 and Systolic (S) BP ≥ 135 mm Hg; (BP will be taken 3 times at 5 minute intervals and the mean of all measurements be considered)

9. History of hypertension, including hypertension controlled with treatment

10. Known history of primary testicular disease or disorders of the hypothalamic-pituitary axis

11. Known hypersensitivity to progestins

12. Family or personal history of venous thromboembolism

13. Benign or malignant liver tumors; active liver disease

14. History of breast carcinoma

15. Known history of reproductive dysfunction including vasectomy or infertility

16. Known history of cardiac, renal, hepatic or prostatic disease

17. A serious systemic disease such as diabetes mellitus or morbid obesity (body weight greater than 120% of ideal body weight or BMI limitation as above)

18. History of sleep apnea

19. Known or suspected alcoholism or drug abuse that may affect metabolism/transformation of steroid hormones and study treatment compliance

20. Known dermatitis or severe skin disorder

21. Partner is known to be pregnant

22. Men desiring fertility within the first 24 weeks of study participation.

Men participating in competitive sports where drug screening for prohibited substances (including anabolic steroids) is routine will be advised of the relative and temporary hazards that participating in this study may have for their fertility or sporting status.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Los Angeles Biomedical Research Institute at Harbor-UCLA	Torrance	California	United States	90502
2	University of Washington	Seattle	Washington	United States	98195

Sponsors and Collaborators

• Health Decisions
• Population Council
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Christina Wang, MD, LA BioMedical Research Institute, Harbor-UCLA
• Principal Investigator: William Bremner, MD, PhD, University of Washington

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Health Decisions
• ClinicalTrials.gov Identifier: NCT00891228
• Other Study ID Numbers: CCN007
• First Posted: May 1, 2009
• Last Update Posted: May 24, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Health Decisions: Contraception; Male Contraception; Suppression of Sperm Production
• Additional relevant MeSH terms: ST 1435; Testosterone

Study Results

Participant Flow

Arm/Group Title	Testosterone Gel 10 g and Nestorone® 0 mg Per Day	Testosterone Gel 10 g and Nestorone® 8 mg Per Day	Testosterone Gel 10 g Plus Nestorone® Gel 12 mg Per Day
Arm/Group Description	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg NES mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg Nestorone® mL gel) by pressing two times with 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head.
Period Title: Overall Study
STARTED	32	33	34
COMPLETED	21	20	19
NOT COMPLETED	11	13	15

Baseline Characteristics

Arm/Group Title	Testosterone Gel 10 g and Nestorone® 0 mg Per Day	Testosterone Gel 10 g and Nestorone® 8 mg Per Day	Testosterone Gel 10 g Plus Nestorone® Gel 12 mg Per Day	Total
Arm/Group Description	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg NES mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg Nestorone® mL gel) by pressing two times with 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head.	Total of all reporting groups
Overall Participants	32	33	34	99
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	32 100%	33 100%	34 100%	99 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	32 100%	33 100%	34 100%	99 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 25%	9 27.3%	10 29.4%	27 27.3%
Not Hispanic or Latino	24 75%	24 72.7%	24 70.6%	72 72.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 3%	0 0%	1 1%
Asian	7 21.9%	1 3%	1 2.9%	9 9.1%
Native Hawaiian or Other Pacific Islander	2 6.3%	1 3%	0 0%	3 3%
Black or African American	5 15.6%	3 9.1%	7 20.6%	15 15.2%
White	16 50%	24 72.7%	25 73.5%	65 65.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 6.3%	3 9.1%	1 2.9%	6 6.1%
Region of Enrollment (participants) [Number]
United States	32 100%	33 100%	34 100%	99 100%

Outcome Measures

1. Primary Outcome

Title	The Number of Men Who Have Suppression of Sperm Production ≤1Million/mL Million/mL When Using a Daily Regimen of Nestorone® Gel (0, 8 or 12 mg) and Testosterone Gel Applied Transdermally.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone Gel 10 g and Nestorone® 0 mg Per Day	Testosterone Gel 10 g and Nestorone® 8 mg Per Day	Testosterone Gel 10 g Plus Nestorone® Gel 12 mg Per Day
Arm/Group Description	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg NES mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg Nestorone® mL gel) by pressing two times with 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head.
Measure Participants	22	18	16
Number [participants]	5 15.6%	15 45.5%	13 38.2%

2. Secondary Outcome

Title	The Number of Men Who Have Suppression of Sperm Production ≤3 Million/mL ≤ 3 Million/mL or Azoospermia When Using a Daily Regimen of Nestorone® Gel (0, 8 or 12 mg) and Testosterone Gel.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone Gel 10 g and Nestorone® 0 mg Per Day	Testosterone Gel 10 g and Nestorone® 8 mg Per Day	Testosterone Gel 10 g Plus Nestorone® Gel 12 mg Per Day
Arm/Group Description	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg NES mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg Nestorone® mL gel) by pressing two times with 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head.
Measure Participants	22	18	16
Number [participants]	5 15.6%	15 45.5%	14 41.2%

3. Secondary Outcome

Title	The Number of Men Who Have Azoospermia
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone Gel 10 g and Nestorone® 0 mg Per Day	Testosterone Gel 10 g and Nestorone® 8 mg Per Day	Testosterone Gel 10 g Plus Nestorone® Gel 12 mg Per Day
Arm/Group Description	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg NES mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg Nestorone® mL gel) by pressing two times with 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head.
Measure Participants	22	18	16
Number [participants]	5 15.6%	14 42.4%	11 32.4%

4. Secondary Outcome

Title	The Impact on Sperm Motility in Men Who Are Not Azoospermic Azoospermic.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

Only subjects with the appropriate amount of data for measurement are represented in the outcome measure data table.

Arm/Group Title	Testosterone Gel 10 g and Nestorone® 0 mg Per Day	Testosterone Gel 10 g and Nestorone® 8 mg Per Day	Testosterone Gel 10 g Plus Nestorone® Gel 12 mg Per Day
Arm/Group Description	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg NES mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg Nestorone® mL gel) by pressing two times with 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head.
Measure Participants	20	7	8
Percent Progressive (week 24)	52.8 (10.70)	31.9 (26.89)	29.6 (17.15)
Percent Non Progressive (week 24)	10.4 (10.72)	7.4 (11.94)	8.3 (4.82)

5. Secondary Outcome

Title	The Impact on Sperm Morphology in Men Who Are Not Azoospermic
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Only subjects with the appropriate amount of data for measurement are represented in the outcome measure data table.

Arm/Group Title	Testosterone Gel 10 g and Nestorone® 0 mg Per Day	Testosterone Gel 10 g and Nestorone® 8 mg Per Day	Testosterone Gel 10 g Plus Nestorone® Gel 12 mg Per Day
Arm/Group Description	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg NES mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg Nestorone® mL gel) by pressing two times with 2 mL dispenser head.	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head.
Measure Participants	21	6	8
Mean (Standard Deviation) [percentage normal morphology]	12.3 (3.87)	10.8 (4.83)	9.1 (4.64)

Adverse Events

Arm/Group Title	Testosterone Gel 10 g and Nestorone® 0 mg Per Day		Testosterone Gel 10 g and Nestorone® 8 mg Per Day		Testosterone Gel 10 g Plus Nestorone® Gel 12 mg Per Day
Arm/Group Description	Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head.		Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg NES mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg Nestorone® mL gel) by pressing two times with 2 mL dispenser head.		Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head. Testosterone: Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily. Nestorone®: Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head.
All Cause Mortality
	Testosterone Gel 10 g and Nestorone® 0 mg Per Day		Testosterone Gel 10 g and Nestorone® 8 mg Per Day		Testosterone Gel 10 g Plus Nestorone® Gel 12 mg Per Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Testosterone Gel 10 g and Nestorone® 0 mg Per Day		Testosterone Gel 10 g and Nestorone® 8 mg Per Day		Testosterone Gel 10 g Plus Nestorone® Gel 12 mg Per Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/33 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Testosterone Gel 10 g and Nestorone® 0 mg Per Day		Testosterone Gel 10 g and Nestorone® 8 mg Per Day		Testosterone Gel 10 g Plus Nestorone® Gel 12 mg Per Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/32 (68.8%)		23/33 (69.7%)		24/34 (70.6%)
Blood and lymphatic system disorders
Iron Deficiency anaemia	0/32 (0%)	0	1/33 (3%)	1	0/34 (0%)	0
Cardiac disorders
Sinus bradycardia	0/32 (0%)	0	1/33 (3%)	1	0/34 (0%)	0
Ear and labyrinth disorders
Ear pain	0/32 (0%)	0	0/33 (0%)	0	1/34 (2.9%)	1
Vertigo	1/32 (3.1%)	1	0/33 (0%)	0	0/34 (0%)	0
Eye disorders
Pinguecula	1/32 (3.1%)	1	0/33 (0%)	0	0/34 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/32 (3.1%)	1	0/33 (0%)	0	0/34 (0%)	0
Abdominal pain upper	2/32 (6.3%)	2	1/33 (3%)	1	1/34 (2.9%)	1
Dental caries	1/32 (3.1%)	1	0/33 (0%)	0	0/34 (0%)	0
Diarrhoea	2/32 (6.3%)	2	1/33 (3%)	1	0/34 (0%)	0
Dyspepsia	1/32 (3.1%)	1	0/33 (0%)	0	0/34 (0%)	0
Food poisoning	0/32 (0%)	0	1/33 (3%)	1	3/34 (8.8%)	3
Gastrooesophageal reflux disease	1/32 (3.1%)	1	0/33 (0%)	0	0/34 (0%)	0
Haematochezia	1/32 (3.1%)	1	0/33 (0%)	0	0/34 (0%)	0
Haemorrhoids	1/32 (3.1%)	1	1/33 (3%)	1	0/34 (0%)	0
Nausea	1/32 (3.1%)	1	1/33 (3%)	1	0/34 (0%)	0
Stomach Discomfort	0/32 (0%)	0	1/33 (3%)	1	0/34 (0%)	0
Stomatitis	1/32 (3.1%)	1	1/33 (3%)	1	0/34 (0%)	0
Toothache	1/32 (3.1%)	1	1/33 (3%)	1	0/34 (0%)	0
Vomiting	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
General disorders
Application site discolouration	0/32 (0%)		1/33 (3%)		0/34 (0%)
Chest pain	0/32 (0%)		1/33 (3%)		0/34 (0%)
Energy Increased	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Fatigue	1/32 (3.1%)		1/33 (3%)		0/34 (0%)
Irritability	1/32 (3.1%)		1/33 (3%)		0/34 (0%)
Oedema peripheral	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Pain	1/32 (3.1%)		1/33 (3%)		0/34 (0%)
Pyrexia	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Immune system disorders
Hypersensitivity	2/32 (6.3%)		0/33 (0%)		0/34 (0%)
Multiple allergies	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Seasonal Allergy	0/32 (0%)		2/33 (6.1%)		0/34 (0%)
Infections and infestations
Cellulitis	0/32 (0%)		1/33 (3%)		0/34 (0%)
Folliculitis	0/32 (0%)		1/33 (3%)		0/34 (0%)
Gastroenteritis	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Gastroenteritis viral	0/32 (0%)		1/33 (3%)		1/34 (2.9%)
Genital infection fungal	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Gonorrhoea	0/32 (0%)		1/33 (3%)		0/34 (0%)
Influenza	3/32 (9.4%)		4/33 (12.1%)		1/34 (2.9%)
Nasopharyngitis	7/32 (21.9%)		4/33 (12.1%)		7/34 (20.6%)
Onychomycosis	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Oral herpes	0/32 (0%)		1/33 (3%)		1/34 (2.9%)
Oropharyngeal gonococcal infection	0/32 (0%)		1/33 (3%)		0/34 (0%)
Pareonychia	0/32 (0%)		1/33 (3%)		0/34 (0%)
Pharyngitis bacterial	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Sinusitis	0/32 (0%)		1/33 (3%)		0/34 (0%)
Tinea versicolour	0/32 (0%)		1/33 (3%)		0/34 (0%)
Upper respiratory tract infection	3/32 (9.4%)		3/33 (9.1%)		3/34 (8.8%)
Urinary tract infection	0/32 (0%)		1/33 (3%)		0/34 (0%)
Viral infection	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Injury, poisoning and procedural complications
Ankle fracture	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Back injury	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Drug administration error	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Injury	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Limb crushing injury	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Limb injury	0/32 (0%)		1/33 (3%)		0/34 (0%)
Post traumatic pain	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Procedural pain	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Road traffic accident	2/32 (6.3%)		1/33 (3%)		0/34 (0%)
Skeletal injury	0/32 (0%)		1/33 (3%)		0/34 (0%)
Investigations
Alanine aminotransferase increased	0/32 (0%)		1/33 (3%)		1/34 (2.9%)
Aspartate aminotransferase increased	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Blood cholesterol increased	1/32 (3.1%)		0/33 (0%)		1/34 (2.9%)
Blood glucose increased	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Blood iron decreased	0/32 (0%)		1/33 (3%)		0/34 (0%)
Blood potassium increased	0/32 (0%)		1/33 (3%)		0/34 (0%)
Blood triglycerides increased	1/32 (3.1%)		1/33 (3%)		0/34 (0%)
Body temperature fluctuation	0/32 (0%)		1/33 (3%)		0/34 (0%)
Heart rate increased	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
semen volume increased	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Sperm count increased	0/32 (0%)		1/33 (3%)		0/34 (0%)
Transaminases increased	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Weight increased	1/32 (3.1%)		4/33 (12.1%)		2/34 (5.9%)
Metabolism and nutrition disorders
Increased appetite	0/32 (0%)		1/33 (3%)		1/34 (2.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/32 (3.1%)		1/33 (3%)		2/34 (5.9%)
Back pain	0/32 (0%)		2/33 (6.1%)		1/34 (2.9%)
Musculoskeletal pain	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Myalgia	1/32 (3.1%)		1/33 (3%)		1/34 (2.9%)
neck pain	0/32 (0%)		1/33 (3%)		0/34 (0%)
pain in extremity	0/32 (0%)		1/33 (3%)		0/34 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Nervous system disorders
Dizziness	0/32 (0%)		1/33 (3%)		0/34 (0%)
headache	9/32 (28.1%)		6/33 (18.2%)		2/34 (5.9%)
Somnolence	0/32 (0%)		1/33 (3%)		0/34 (0%)
Psychiatric disorders
aggression	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Anorgasmia	0/32 (0%)		1/33 (3%)		0/34 (0%)
depressed mood	0/32 (0%)		1/33 (3%)		0/34 (0%)
depression	1/32 (3.1%)		0/33 (0%)		1/34 (2.9%)
Libido decreased	1/32 (3.1%)		2/33 (6.1%)		0/34 (0%)
insomnia	2/32 (6.3%)		2/33 (6.1%)		2/34 (5.9%)
libido increased	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
mood altered	0/32 (0%)		1/33 (3%)		0/34 (0%)
mood swings	0/32 (0%)		2/33 (6.1%)		1/34 (2.9%)
nightmare	0/32 (0%)		1/33 (3%)		0/34 (0%)
Renal and urinary disorders
dysuria	0/32 (0%)		1/33 (3%)		0/34 (0%)
pollakiuria	0/32 (0%)		1/33 (3%)		0/34 (0%)
Reproductive system and breast disorders
ejaculation disorder	0/32 (0%)		1/33 (3%)		0/34 (0%)
genital rash	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
gynaecomastia	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
nipple pain	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
varicocele	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
Respiratory, thoracic and mediastinal disorders
asthma	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
cough	0/32 (0%)		1/33 (3%)		0/34 (0%)
oropharyngeal pain	2/32 (6.3%)		2/33 (6.1%)		2/34 (5.9%)
postnasal drip	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
pulmonary congestion	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
rhinitis allergic	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
sinus congestion	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Skin and subcutaneous tissue disorders
acne	9/32 (28.1%)		7/33 (21.2%)		5/34 (14.7%)
dry skin	1/32 (3.1%)		2/33 (6.1%)		1/34 (2.9%)
Erythema	0/32 (0%)		1/33 (3%)		0/34 (0%)
heat rash	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
night sweats	0/32 (0%)		1/33 (3%)		1/34 (2.9%)
Pruritus	0/32 (0%)		1/33 (3%)		1/34 (2.9%)
skin exfoliation	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
Surgical and medical procedures
mole excision	0/32 (0%)		0/33 (0%)		1/34 (2.9%)
oral surgery	1/32 (3.1%)		0/33 (0%)		0/34 (0%)
tooth repair	0/32 (0%)		1/33 (3%)		0/34 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.