Study of Serum Testosterone and Nestorone in Females After Secondary Exposure to Nestorone ® (NES) + Testosterone (T) Combined Gel Applied to Shoulders and Upper Arms in Males

Study Overview
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Brief Summary
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This is a two-center, open-label study conducted in healthy male and female volunteers at two academic research centers. The study will consist of three single applications of the Nestorone (NES) + testosterone (T) combined gel on the shoulders/upper arms of male participants followed 2 hours later by supervised skin contact by the non-dosed female participants on the application site on days 1, 8, and 15. Effect of Washing or Clothing Barrier to the Application will be assessed.

Detailed Description
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This is a two-center, open-label study conducted in healthy male and female volunteers at two academic research centers. The study will consist of three single applications of the Nestorone (NES) + testosterone (T) combined gel on the shoulders/upper arms of male participants followed 2 hours later by supervised skin contact by the non-dosed female participants on the application site on days 1, 8, and 15. On day 1, the male participant will wear a 100% cotton T-shirt over the application area before skin contact with the female. On day 8, the male participant will shower approximately 1 hour and 45 minutes after gel application and engage in skin contact with the female participant (2 hours after gel application) after washing the area with soap and water then drying it. A measurement of residual Nestorone and testosterone will be taken from the male's skin on a single location of the application site using adhesive D-square strips 90 minutes after application (30 minutes before shower/90 minutes after gel application) and 30 minutes after the shower and rubbing (150 minutes after application). On day 15, there will be no shower or clothing barrier for the male participant before skin contact with the female participant. A measurement of residual Nestorone and testosterone will be taken from a single location of the application using adhesive D-square strips site 90 minutes and 150 minutes after the application. An end of study/exit visit will occur for both male and female participants two weeks after treatment completion.

Official Title
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An Open-Label Study of Serum Testosterone and Nestorone in Females After Secondary Exposure to Nestorone ® (NES) + Testosterone (T) Combined Gel Applied to Shoulders and Upper Arms in Males: Effect of Washing or Clothing Barrier to the Application

Conditions
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Healthy Men, Male Contraception, Healthy Women, Product Transference

Intervention / Treatment
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* Drug: Nestorone + Testosterone Combination Gel


Participation Criteria
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Eligibility Criteria
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Inclusion Male participant - Inclusion Criteria Men who meet all the following criteria will be eligible for enrollment in the trial: Good health as confirmed by medical history, physical examination, and clinical laboratory tests of blood and urine at the time of screening; 18 to 50 years of age; BMI ≥ 18 and < 35 kg/m2; No history of androgen use prior to the first screening visit as follows: 1 month prior for oral or transdermal androgen, 3 months prior for Testosterone cypionate or enanthate injection, 6 months prior for Testosterone undecanoate injection; Agreement to use a recognized effective method of short acting contraception with his partner (i.e. at a minimum use double-barrier method such as a condom with spermicide) during the entire study; In the opinion of the investigator, male subject is willing and able to comply with the protocol; Provision of valid, written and informed consent. Female participant - Inclusion Criteria Women who meet all the following criteria will be eligible for enrollment in the trial: Good general health (BMI ≥18 and <30 kg/m2)with no chronic medical conditions that result in periodic exacerbations which require significant medical care; Aged between 18 and 40 years, at the enrollment visit; Not pregnant and not breastfeeding. Agreement to use a recognized effective method of contraception throughout the study Willingness and ability to provide valid, written and informed consent and to comply with the protocol; No desire for pregnancy within the next 6 months. Exclusion Male participant - Exclusion Criteria Men who meet any of the following criteria are not eligible for enrollment in the trial: Men participating in another clinical trial involving an investigational drug within the last 30 days prior to the first screening visit. Men not living in the catchment area of the study site or within a reasonable travel time from the site. Any clinically significant abnormal findings at screening per the Investigator's medical judgement. Elevated PSA (e.g. levels ≥ 4 ng/mL), according to study site's local laboratory reference normal values for adult men. Abnormal serum chemistry values that may indicate clinically significant liver or kidney dysfunction. Other abnormal laboratory values may also be exclusionary, if so considered by the investigator to be clinically significant. Use of androgens or other anabolic steroids that may affect testosterone measurements Diastolic blood pressure (DBP) ≥ 85 and Systolic blood pressure (SBP) ≥ 135 mm Hg; (BP will be taken three times at approximately 5 minute intervals and the mean of the 3 measurements will be considered). History of hypertension (well-controlled treated hypertension (< 135/85) is allowed). Known history of primary testicular disease or disorders of the hypothalamic-pituitary axis. Known hypersensitivity to progestins or testosterone. History of prostate or breast carcinoma Significant lower urinary obstructive symptoms (IPSS > 19). Known history of significant cardiac, renal, hepatic or prostatic disease. History of thromboembolic disease. A serious systemic disease such as diabetes mellitus (including diabetes controlled with treatment), HIV, or morbid obesity. Current active or ongoing Hepatitis infection Known or suspected current alcohol dependence syndrome, chronic marijuana use, or any illicit drug use that may affect metabolism/transformation of steroid hormones and study treatment compliance. Known active or chronic dermatitis or other severe skin disorder. Desiring fertility within 6 months of study participation. History of severe depression or other serious mental health disorder. 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 sporting status. Female participant - Exclusion Criteria Women who meet any of the following criteria are not eligible for enrollment in the trial: Desire to become pregnant during the study. Breastfeeding Known or suspected current alcoholism or drug abuse. History of thrombosis Serum testosterone outside normal reference ranges by local laboratory standards or evidence of hirsutism (modified Ferriman-Galwey score > 8) Participation in another clinical trial involving an investigational drug within the last 30 days prior to the first screening visit. Current pregnancy. Known hypersensitivity to progestins or testosterone. Any clinically significant abnormal findings at screening per the Investigator's medical judgement. Use of androgens or other anabolic steroids that may affect testosterone measurements. Known active or chronic dermatitis or other severe skin disorder. Known or suspected current alcohol dependence syndrome, chronic marijuana use, or any illicit drug use that may affect metabolism/transformation of steroid hormones and study treatment compliance. Not living in the catchment area of the study site or within a reasonable travel time from the site.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nestorone (NES) + testosterone (T) combined gel<br>A combination gel with Nestorone® (NES) and Testosterone (T) applied transdermally. The volume of gel to be applied will be approximately 5 mL. This gel volume will contain 62.5 mg of T that will deliver approximately 6 mg T to the body per day and will also contain 8.3 mg of NES that will deliver about 0.8 mg NES to the body per day (NES 8 mg/d + T 60 mg/d (NES8/T60) gel) in 5 ml of combined gel. | Drug: Nestorone + Testosterone Combination Gel<br>* The combined gel is a transdermal treatment that will be applied as three single applications to a male subject's arms and shoulders on three different treatment days. The formulation will be a hydro alcoholic gel containing about 1.43% T (14.3 mg T/g gel). About 9 to 14% of the steroid (T or NES) in the gel applied is available to the body. The amount of gel to be applied each application will be approximately 5 mL in volume. The gel application volume will contain 62.5 mg of T that will deliver approximately 6 mg T to the body per day (Swerdloff et al., 2000; Wang et al., 2000). This gel volume will also contain 8.3 mg of NES that will deliver about 0.8 mg of NES to the body per day (NES 8 mg/d + T 60 mg/d (NES8/T60) gel).<br>* Other names: NES8/T60;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate in female participants by assessing changes from baseline up to 48 hours for serum testosterone levels in Cavg after secondary exposure to Nestorone + Testosterone Combination Gel | female serum testosterone changes in cavg | 17 days | 
| Evaluate in female participants by assessing changes from baseline up to 48 hours for serum testosterone levels in Cmax after secondary exposure to Nestorone + Testosterone Combination Gel | female serum testosterone changes in cmax | 17 days | 
| Evaluate in female participants by assessing changes from baseline up to 48 hours for serum testosterone levels in Cmin after secondary exposure to Nestorone + Testosterone Combination Gel | female serum testosterone changes in cmin | 17 days | 
| Evaluate in female participants by assessing Nestorone levels after secondary exposure to NES/T by presenting Cavg | female nestorone levels in cavg | 17 days | 
| Evaluate in female participants by assessing Nestorone levels after secondary exposure to NES/T by presenting Cmax | female nestorone levels in cmax | 17 days | 
| Evaluate in female participants by assessing Nestorone levels after secondary exposure to NES/T by presenting Cmin | female nestorone levels in cmin | 17 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK of testosterone in males after wearing a T shirt and after washing will be compared to serum testosterone PK after application of the combined gel without washing using AUC (0-t, where t is the last time-point with measurable concentration) | PK of T in males after NES/T with a T-shirt and after washing | 15 days | 
| PK of Nestorone in males after wearing a T shirt and after washing will be compared to serum Nestorone PK after application of the combined gel without washing using AUC (0-t, where t is the last time-point with measurable concentration) | PK of NES in males after NES/T with a T-shirt and after washing | 15 days | 
| PK of serum testosterone in males after applying NES/T gel with or without T shirt and with washing will be compared to baseline serum testosterone | male changes in serum T compared to baseline | 15 days | 
| Average testosterone levels 90 and 150 minutes after each application in men (over a 15 day period) as measured by adhesive D-square strips with and without showering. | T levels compared with and without showering | 15 days | 
| Average Nestorone levels 90 and 150 minutes after each application in men (over a 15 day period) as measured by adhesive D-square strips with and without showering. | NES levels compared with and without showering | 15 days | 
| Incidence of adverse events and serious adverse events for males | Male AEs | 31 days | 
| Incidence of adverse events and serious adverse events for females | Female AEs | 31 days | 
| Changes from baseline in safety labs for males | Male lab changes | 15 days | 
| Changes from baseline in safety labs for males | Female lab changes | 31 days | 
| Percentage of females with increased (relative to baseline) hirsutism at each visit. | Female hirsutism changes | 31 days | 
| Percentage of females with increased (relative to baseline) acne at each visit. | Female acne changes | 31 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gel, Healthy Men, Male Contraception, Healthy Women, Transfer, Transference, Nestorone, Testosterone