Clinical trial NCT02432261: Evaluate the Pharmacokinetics and Gonadotropin Suppression of Nestorone®-Testosterone (NES/T) Combination Gel in Men
Official title: A Randomized, Two Center, Double-Blind Trial to Evaluate the Pharmacokinetics and Gonadotropin Suppression of Nestorone®-Testosterone (NES/T) Combination Gel in Healthy Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: spermatogenesis
androgen
male contraception
Lead sponsor: Health Decisions
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2015-05-04
Enrollment: 44
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Gonadotropin Suppression
timeFrame: 4 weeks
Secondary outcomes:
measure: Gonadotropin and Follicle-stimulating Hormone Suppression
timeFrame: 4 weeks
measure: Change in LH and FSH Concentrations
timeFrame: 4 weeks
measure: Acceptability and Satisfaction as Measured by the Contraceptive Gel Acceptability and Satisfaction Questionnaire by Comparing T and NES Serum Concentrations.
timeFrame: 4 weeks
measure: T Serum Concentrations
timeFrame: 8 weeks
measure: Secondary Outcome # 6 Part 1a: A Composite Safety of the Combined Gel Determined by Outcomes of CBC (Hemoglobin)
timeFrame: 4 weeks
measure: Assessing Sexual Function by Compare Gonadotropin Suppressive Activity of T and NES Against T Alone Through the Psychosexual Daily Questionnaire.
timeFrame: 4 weeks
measure: Secondary Outcome # 6 Part 2a: A Composite Safety of the Combined Gel Determined by Outcomes of Chemistry
timeFrame: 4 weeks
measure: Secondary Outcome # 6 Part 3a: A Composite Safety of the Combined Gel Determined by Outcomes of Vitals (Blood Pressure)
timeFrame: 4 weeks
measure: Secondary Outcome # 6 Part 4: A Composite Safety of the Combined Gel Determined by Outcomes of Physical Changes
timeFrame: 4 weeks
measure: Secondary Outcome # 6 Part 5: A Composite Safety of the Combined Gel Determined by Outcomes of Psychosexual Questionnaires
timeFrame: 4 weeks
measure: Secondary Outcome # 6 Part 3: A Composite Safety of the Combined Gel Determined by Outcomes of Patient Health Questionnaires
timeFrame: 4 weeks
measure: NES Serum Concentrations
timeFrame: 8 weeks
measure: Secondary Outcome # 6 Part 1b: A Composite Safety of the Combined Gel Determined by Outcomes of CBC (WBC)
timeFrame: 4 weeks
measure: Secondary Outcome # 6 Part 1c: A Composite Safety of the Combined Gel Determined by Outcomes of CBC (Hematocrit)
timeFrame: 4 weeks
measure: Secondary Outcome # 6 Part 2b: A Composite Safety of the Combined Gel Determined by Outcomes of Chemistry
timeFrame: 4 weeks
measure: Secondary Outcome # 6 Part 3b: A Composite Safety of the Combined Gel Determined by Outcomes of Vitals (Weight)
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Torrance
country: United States
facility: LA Biomedical Research Institute
state: California
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Research Site
name: Christina Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Research Site
name: William Bremner, MD
role: PRINCIPAL_INVESTIGATOR
References: