Healthy Men, Healthy Women, Male Contraception, Product Transference
Conditions
Keywords
Healthy Men, Male Contraception, Healthy Women, Transfer, Transference, Gel, Nestorone, Testosterone
Brief summary
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
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.
Interventions
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).
Sponsors
Kimberly Myer
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
University of Washington
Population Council
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion Male participant - Inclusion Criteria Men who meet all the following criteria will be eligible for enrollment in the trial: 1. Good health as confirmed by medical history, physical examination, and clinical laboratory tests of blood and urine at the time of screening; 2. 18 to 50 years of age; 3. BMI ≥ 18 and \< 35 kg/m2; 4. No history of androgen use prior to the first screening visit as follows: 1. 1 month prior for oral or transdermal androgen, 2. 3 months prior for Testosterone cypionate or enanthate injection, 3. 6 months prior for Testosterone undecanoate injection; 5. 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; 6. In the opinion of the investigator, male subject is willing and able to comply with the protocol; 7. 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: 1. Good general health (BMI ≥18 and \<30 kg/m2)with no chronic medical conditions that result in periodic exacerbations which require significant medical care; 2. Aged between 18 and 40 years, at the enrollment visit; 3. Not pregnant and not breastfeeding. 4. Agreement to use a recognized effective method of contraception throughout the study 5. Willingness and ability to provide valid, written and informed consent and to comply with the protocol; 6. 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: 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 area of the study site or within a reasonable travel time from the site. 3. Any clinically significant abnormal findings at screening per the Investigator's medical judgement. 4. Elevated PSA (e.g. levels ≥ 4 ng/mL), according to study site's local laboratory reference normal values for adult men. 5. 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. 6. Use of androgens or other anabolic steroids that may affect testosterone measurements 7. 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). 8. History of hypertension (well-controlled treated hypertension (\< 135/85) is allowed). 9. Known history of primary testicular disease or disorders of the hypothalamic-pituitary axis. 10. Known hypersensitivity to progestins or testosterone. 11. History of prostate or breast carcinoma 12. Significant lower urinary obstructive symptoms (IPSS \> 19). 13. Known history of significant cardiac, renal, hepatic or prostatic disease. 14. History of thromboembolic disease. 15. A serious systemic disease such as diabetes mellitus (including diabetes controlled with treatment), HIV, or morbid obesity. 16. Current active or ongoing Hepatitis infection 17. 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. 18. Known active or chronic dermatitis or other severe skin disorder. 19. Desiring fertility within 6 months of study participation. 20. History of severe depression or other serious mental health disorder. 21. 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 -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline (Cavg) for Serum Testosterone Levels in Females After Secondary Exposure to Nestorone + Testosterone Combination Gel | Baseline and 48 hours after each intervention (day 1 for t-shirt, day 8 for shower and dried, and day 15 for no shower or t-shirt) | 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 summarized for each of the 3 types of skin contact between the man and woman. |
| Changes From Baseline (Cmin) for Serum Testosterone Levels in Females After Secondary Exposure to Nestorone + Testosterone Combination Gel | Baseline and 48 hours after each intervention (day 1 for t-shirt, day 8 for shower and dried, and day 15 for no shower or t-shirt) | 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 summarized for each of the 3 types of skin contact between the man and woman. |
| Changes From Baseline (Cmax) for Serum Testosterone Levels in Females After Secondary Exposure to Nestorone + Testosterone Combination Gel | Baseline and 48 hours after each intervention (day 1 for t-shirt, day 8 for shower and dried, and day 15 for no shower or t-shirt) | 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 summarized for each of the 3 types of skin contact between the man and woman. |
| Changes From Baseline (Cmin) for Serum Nestorone Levels in Females After Secondary Exposure to Nestorone + Testosterone Combination Gel | Baseline and 48 hours after each intervention (day 1 for t-shirt, day 8 for shower and dried, and day 15 for no shower or t-shirt) | Evaluate in female participants by assessing changes from baseline up to 48 hours for serum Nestorone levels in Cmin after secondary exposure to Nestorone + Testosterone Combination Gel summarized for each of the 3 types of skin contact between the man and woman. |
| Changes From Baseline (Cmax) for Serum Nestorone Levels in Females After Secondary Exposure to Nestorone + Testosterone Combination Gel | Baseline and 48 hours after each intervention (day 1 for t-shirt, day 8 for shower and dried, and day 15 for no shower or t-shirt) | Evaluate in female participants by assessing changes from baseline up to 48 hours for serum Nestorone levels in Cmax after secondary exposure to Nestorone + Testosterone Combination Gel summarized for each of the 3 types of skin contact between the man and woman. |
| Changes From Baseline (Cavg) for Serum Nestorone Levels in Females After Secondary Exposure to Nestorone + Testosterone Combination Gel | Baseline and 48 hours after each intervention (day 1 for t-shirt, day 8 for shower and dried, and day 15 for no shower or t-shirt) | Evaluate in female participants by assessing changes from baseline up to 48 hours for serum Nestorone levels in Cavg after secondary exposure to Nestorone + Testosterone Combination Gel summarized for each of the 3 types of skin contact between the man and woman. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK of T in Males After NES/T With a T-shirt and After Washing | Baseline and 24 hours after each intervention (day 1 for t-shirt, day 8 for shower and dried, and day 15 for no shower or t-shirt) | 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 NES in Males After NES/T With a T-shirt and After Washing | Baseline and 24 hours after each intervention (day 1 for t-shirt, day 8 for shower and dried, and day 15 for no shower or t-shirt) | 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) |
| Average Testosterone Levels 90 and 150 Minutes After Each Application in Men | Visits 5 and 7 (Days 8 and 15) | 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 showering (Visit 5) and without showering (Visit 7). |
| Average Nestorone Levels 90 and 150 Minutes After Each Application in Men | Visits 5 and 7 (Days 8 and 15) | 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 showering (Visit 5) and without showering (Visit 7). |
| Incidence of Adverse Events and Serious Adverse Events for Males | 31 days | Male AEs |
| Incidence of Adverse Events and Serious Adverse Events for Females | 31 days | Female AEs |
| Changes From Baseline in Hematology Safety Labs for Females | Screening and Visit 7, up to 43 days | Changes from baseline in hematology parameters for females measured at Screening (Day -28 to 0) and Visit 7 (Day 15) |
| Changes From Baseline in Hematology Safety Labs for Males | Screening and Visit 7, up to 43 days | Changes from baseline in hematology parameters for males measured at Screening (Day -28 to 0) and Visit 7 (Day 15) |
| Changes From Baseline in Clinical Chemistry Safety Labs for Females | Screening and Visit 7, up to 43 days | Changes from baseline in clinical chemistry parameters for females measured at Screening (Day -28 to 0) and Visit 7 (Day 15) |
| Changes From Baseline in Clinical Chemistry Safety Labs for Males | Screening and Visit 7, up to 43 days | Changes from baseline in clinical chemistry parameters for males measured at Screening (Day -28 to 0) and Visit 7 (Day 15) |
| Percentage of Females With Increased (Relative to Baseline) Hirsutism at Each Visit. | Screening, Visit 4 (Day 3), Visit 6 (Day 10), Visit 8 (Day 17), and Visit 9 (Day 31) | Female hirsutism changes assessed at Screening, Visits 4, 6, 8, and 9 |
| Percentage of Females With Increased (Relative to Baseline) Acne at Each Visit. | Screening, Visit 4 (Day 3), Visit 6 (Day 10), Visit 8 (Day 17), and Visit 9 (Day 31) | Female acne changes assessed at Screening, Visits 4, 6, 8, and 9 |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORChristina Wang, MD
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
PRINCIPAL_INVESTIGATORBradley Anawalt, MD
University of Washington
Participant flow
Pre-assignment details
13 partners were enrolled (13 females and 13 males); Planned enrollment was 24 but study enrolled 26 participants.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical Female Subjects <=18 years | 0 Participants |
| Age, Categorical Female Subjects >=65 years | 0 Participants |
| Age, Categorical Female Subjects Between 18 and 65 years | 13 Participants |
| Age, Categorical Male Subjects <=18 years | 0 Participants |
| Age, Categorical Male Subjects >=65 years | 0 Participants |
| Age, Categorical Male Subjects Between 18 and 65 years | 13 Participants |
| Age, Continuous Female Subjects | 25.9 years STANDARD_DEVIATION 4.35 |
| Age, Continuous Male Subjects | 29.4 years STANDARD_DEVIATION 7.82 |
| Ethnicity (NIH/OMB) Female Subjects Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Female Subjects Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Female Subjects Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) Male Subjects Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Male Subjects Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Male Subjects Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Female Subjects American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Female Subjects Asian | 1 Participants |
| Race (NIH/OMB) Female Subjects Black or African American | 1 Participants |
| Race (NIH/OMB) Female Subjects More than one race | 3 Participants |
| Race (NIH/OMB) Female Subjects Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Female Subjects Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) Female Subjects White | 7 Participants |
| Race (NIH/OMB) Male Subjects American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Male Subjects Asian | 1 Participants |
| Race (NIH/OMB) Male Subjects Black or African American | 3 Participants |
| Race (NIH/OMB) Male Subjects More than one race | 0 Participants |
| Race (NIH/OMB) Male Subjects Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Male Subjects Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) Male Subjects White | 6 Participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 6 / 26 | 1 / 13 | 5 / 13 |
| serious Total, serious adverse events | 0 / 26 | 0 / 13 | 0 / 13 |
Outcome results
None listed