Evaluate the Pharmacokinetics and Gonadotropin Suppression of Nestorone®-Testosterone (NES/T) Combination Gel in Men

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Nestorone® /testosterone gel; Drug: Testosterone only gel

• Registration Number: NCT02432261
• Lead Sponsor: Kimberly Myer

Brief Summary

This is a prospective, randomized, double-blinded, two-center trial to evaluate the gonadotropin suppressive activity of transdermal treatment with a combined NES/T gel, or T gel alone, for 28 days.

Detailed Description

A total of 45 subjects will be enrolled and randomized in a 2:1 ratio to one of two treatment groups. A description of each group is as follows:

* Group 1 (30 subjects): 5.0 mL of the 1.62% combined gel (containing 8.3 mg NES + 62.5 mg T) applied each day on the arms and shoulders

* Group 2 (15 subjects): 4.4 mL of the 1.62% AndrogelTM (containing 62.7 mg T) applied each day to the arms and shoulders

The total duration of treatment will be 28 days followed by a 72 hour sampling period to assess half-life and a recovery period of at least 28 days, at which point the subjects will return to the clinic for an end of study visit.

Study Timeline

• Study First Submitted: 2015-03-19
• Study Start: 2015-04
• Study First Submitted QC: 2015-04-30
• Study First Posted: 2015-05-04
• Primary Completion: 2016-03
• Study Completion: 2016-03
• Results First Submitted: 2024-04-01
• Status Verified: 2025-02
• Results First Submitted QC: 2025-02-12
• Last Update Submitted: 2025-02-12
• Results First Posted: 2025-02-13
• Last Update Posted: 2025-02-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 44

Inclusion Criteria

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, condom for the male partner and an effective contraception for the female partner) 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.
8. Sperm concentration ≥ 15 million sperm per milliliter ejaculate.

Exclusion Criteria

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 physical 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;
6. Use of androgens or body building substances within 6 months before first screening visit;
7. Diastolic blood pressure (DBP) > 80 and/or Systolic (SBP) > 130 mm Hg;
8. EKG abnormal and clinically significant and QTC level longer than 450msec;
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 or androgen;
12. Family or personal history of venous thromboembolism;
13. Benign or malignant liver tumors; active liver disease;
14. Known history of reproductive dysfunction including vasectomy or infertility;
15. Known history of cardiovascular, renal, hepatic or prostatic disease;
16. 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);
17. Known or suspected alcoholism or drug abuse that may affect metabolism/transformation of steroid hormones and study treatment compliance;
18. Known dermatitis or severe skin disorder;
19. Moderate or severe depression as determined by PHQ-9 score >15;
20. Partner is known to be pregnant;
21. Known or suspected breast or prostate cancer;
22. Allergic to any ingredient in testosterone/nestorone gel, including alcohol;
23. Known history of untreated sleep apnea;
24. International Prostate Symptom Score (IPSS) greater than or equal to 15.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	Nestorone® /testosterone gel	5.0 mL of the 1.62% Nestorone® /testosterone gel (containing 8.3 mg NES + 62.5 mg T) applied each day on the arms and shoulders
Group 2	Testosterone only gel	4.4 mL of the 1.62% Testosterone only gel (AndrogelTM) (containing 62.7 mg T) applied each day to the arms and shoulders

Primary Outcome Measures

Name	Time	Method
Gonadotropin Suppression	4 weeks	To quantify the gonadotropin suppressive activity of 4 weeks daily therapy of a combination transdermal gel containing 8.3 mg Nestorone® (NES) gel and 62.5 mg (1.62%) testosterone (T) gel, and of T gel (1.62%) alone. Specifically, the proportion (and 95% CI) of men who suppress both gonadotropins (luteinizing hormone \[LH\] and follicle-stimulating hormone \[FSH\]) to ≤ 1 IU/L in each group, will be quantified.

Secondary Outcome Measures

Name	Time	Method
Gonadotropin and Follicle-stimulating Hormone Suppression	4 weeks	• To quantify the proportion (and 95% CI) of men who suppress both gonadotropins (luteinizing hormone \[LH\] and follicle-stimulating hormone \[FSH\]) to the detection limit of the assay in each group.
Change in LH and FSH Concentrations	4 weeks	• To quantify the median percent change from baseline to week 4 and interquartile range for serum gonadotropins (LH and FSH) concentrations for each treatment group.
Acceptability and Satisfaction as Measured by the Contraceptive Gel Acceptability and Satisfaction Questionnaire by Comparing T and NES Serum Concentrations.	4 weeks	A simple acceptability questionnaire used previously in male CCTN studies was administered at treatment Day 28 (28, 29) for subjects to answer questions about the acceptability of gel as a product and as a method for contraception over the preceding 4 weeks.
T Serum Concentrations	8 weeks
Secondary Outcome # 6 Part 1a: A Composite Safety of the Combined Gel Determined by Outcomes of CBC (Hemoglobin)	4 weeks	General composite safety as measured various times during the study by CBC-Hemoglobin
Assessing Sexual Function by Compare Gonadotropin Suppressive Activity of T and NES Against T Alone Through the Psychosexual Daily Questionnaire.	4 weeks	Sexual activity was rated on a scale from 0 (not at all) to 7 (very high enjoyment/pleasure). Erections were rated on a scale of 0 (not satisfactory) to 7 (very satisfactory). Results are change from baseline to final treatment evaluation.
Secondary Outcome # 6 Part 4: A Composite Safety of the Combined Gel Determined by Outcomes of Physical Changes	4 weeks	Change from baseline to final treatment evaluation
Secondary Outcome # 6 Part 5: A Composite Safety of the Combined Gel Determined by Outcomes of Psychosexual Questionnaires	4 weeks	Change from baseline to final treatment evaluation. Sexual motivation was rated on a scale of 0 (none) to 7 (very high). Erections were rated on a scale of 0 (not satisfactory) to 7 (very satisfactory).
Secondary Outcome # 6 Part 3: A Composite Safety of the Combined Gel Determined by Outcomes of Patient Health Questionnaires	4 weeks	PHQ-9 Total Score: Change from baseline to final treatment evaluation. The Patient Health Questionnaire (PHQ)-9 is a self-administered instrument for screening, monitoring and diagnosis of depression. This questionnaire can be used repeatedly to monitor improvement or worsening of symptoms. Scale range is from 0 (not at all) to 3 (nearly every day).
Secondary Outcome # 6 Part 2a: A Composite Safety of the Combined Gel Determined by Outcomes of Chemistry	4 weeks	Change from baseline to final treatment evaluation-Total Cholesterol, Triglycerides, HDL
Secondary Outcome # 6 Part 3a: A Composite Safety of the Combined Gel Determined by Outcomes of Vitals (Blood Pressure)	4 weeks	Change from baseline to final treatment evaluation
NES Serum Concentrations	8 weeks
Secondary Outcome # 6 Part 1b: A Composite Safety of the Combined Gel Determined by Outcomes of CBC (WBC)	4 weeks	General composite safety as measured various times during the study by CBC - WBC
Secondary Outcome # 6 Part 1c: A Composite Safety of the Combined Gel Determined by Outcomes of CBC (Hematocrit)	4 weeks	General composite safety as measured various times during the study by CBC-Hematocrit
Secondary Outcome # 6 Part 2b: A Composite Safety of the Combined Gel Determined by Outcomes of Chemistry	4 weeks	Change from baseline to final treatment evaluation-ALT, AST
Secondary Outcome # 6 Part 3b: A Composite Safety of the Combined Gel Determined by Outcomes of Vitals (Weight)	4 weeks	Change from baseline to final treatment evaluation

Trial Locations

Locations (2)

LA Biomedical Research Institute; 🇺🇸 Torrance, California, United States

University of Washington; 🇺🇸 Seattle, Washington, United States