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Trial record 1 of 1 for:    NCT03452111
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Study of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception

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ClinicalTrials.gov Identifier: NCT03452111
Recruitment Status : Recruiting
First Posted : March 2, 2018
Last Update Posted : November 7, 2018
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Population Council
Information provided by (Responsible Party):
Health Decisions

Tracking Information
First Submitted Date  ICMJE February 23, 2018
First Posted Date  ICMJE March 2, 2018
Last Update Posted Date November 7, 2018
Actual Study Start Date  ICMJE October 25, 2018
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2018)
Contraceptive efficacy provided by the daily application of NES/T gel for 52 weeks during the efficacy phase of the study determined using Kaplan-Meier methods to estimate the 12 month cumulative pregnancy probability in the typical use population. [ Time Frame: 12 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03452111 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2018)
  • Suppression of spermatogenesis induced by daily use of the NES/T gel as assessed by semen analyses using number of subjects with sperm concentration <1 million (M)/mL during the suppression phase of the study. [ Time Frame: 20 weeks ]
  • Maintenance of suppression of spermatogensis induced by daily use of the NE/T gel as assessed by semen analyses using number of subjects with sperm concentration <1 million (M)/mL during the 52 week efficacy phase of the study. [ Time Frame: 52 weeks ]
  • Changes from baseline in Follicle Stimulating Hormone (FSH) with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in Luteinizing Hormone (LH) with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in Sex Hormone Binding Globulin (SHBG) with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in Testosterone with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in Nestorone with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Incidence of treatment emergent adverse events with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in sodium with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in potassium with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in chloride with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in bicarbonate with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in fasting glucose with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in blood urea nitrogen with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in creatinine with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in calcium with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in total bilirubin with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in alkaline phosphatase with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in alanine aminotransferase with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in aspartate transaminase with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in albumin with daily use of the NES/T gel. [ Time Frame: 24 months ]
  • Changes from baseline in mood with daily use of the NES/T gel using the Patient Health Questionnaire-9. [ Time Frame: 24 months ]
  • Changes from baseline in sexual function with daily use of the NES/T gel using the psychosexual daily questionnaire. [ Time Frame: 24 months ]
  • Changes from baseline in prostate function with daily use of NES/T gel using the International Prostate Symptom Score. [ Time Frame: 24 months ]
  • Acceptability of NES/T gel as a contraceptive among male and female participants using the acceptability questionnaires. [ Time Frame: 24 months ]
  • Length of time to recovery of spermatogenesis after daily use of NES/T gel as assessed by sperm concentration > 15 million (M)/mL during the recovery phase. [ Time Frame: 24 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception
Official Title  ICMJE Clinical Evaluation of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception
Brief Summary The long term objective is to develop a gel to be used as a male contraceptive.
Detailed Description

This is a prospective, phase IIb, open label, single arm, multicenter study. The study protocol consists of a screening phase lasting 4 to 8 weeks, a suppression phase estimated up to 20 weeks, a 52-week maintenance/efficacy phase, and a 24-week (estimated) recovery phase.

The study will involve approximately 420 couples recruited throughout the CCTN that meet eligibility criteria. The nine sites propose to enroll up to 420 couples (about 30 to 60 couples per site) with a goal of obtaining 200 couples completing the contraceptive efficacy phase of the study. The study has four phases (screening phase, suppression phase, efficacy phase and recovery phase) with monthly visits to provide the male participants with the NES-8/T-62 gel, to encourage adherence, to monitor for possible side effects, and to quantify semen parameters. The female will be contacted monthly and come in for a visit every three months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE
  • Healthy
  • Men
  • Male Contraception
Intervention  ICMJE Drug: Nestorone + Testosterone Combination Gel
The combined gel is a transdermal treatment that will be applied daily for 52 weeks to a male subject's arms and shoulders. 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 mg of T that will deliver approximately 6 mg T to the body per day. This gel volume will also contain 8 mg of NES that will deliver about 0.8 mg of NES to the body per day (NES 8 mg/d + T 62 mg/d (NES8/T62) gel).
Other Names:
  • NES/T gel
  • NES-8/T-62
Study Arms  ICMJE Experimental: Nestorone (NES) + testosterone (T) combined gel
A combination Gel with Nestorone® (NES) and Testosterone (T) applied transdermally. The amount of gel to be applied daily will be approximately 5 mL in volume (2.5 mL to each shoulder and upper arm per day). This daily gel volume will contain approximately 62 mg of T that will deliver 6 mg T to the body per day and will also contain 8 mg of NES that will deliver about 0.8 mg NES to the body per day (NES 8 mg/day + T 62 mg/day (NES-8/T-62) gel).
Intervention: Drug: Nestorone + Testosterone Combination Gel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 28, 2018)
420
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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, at the enrollment visit;
  3. BMI < 33 kg/m2;
  4. No history of androgen use in the six months prior to the first screening visit;
  5. Agreement to use an effective method of contraception with his female partner (refer to Appendix 11 for acceptable forms of contraception) during the suppression and recovery phases and then only use the experimental method during the efficacy phase of the study;
  6. In the opinion of the investigator, the male subject is willing and able to comply with the protocol;
  7. The subject is legally competent, has been informed of the nature, the scope and the relevance of the study, voluntarily agrees to participation and the study's provisions and has duly signed the informed consent form (ICF);
  8. Sexually active with a female partner (as specified below) with whom he has been in a stable, mutually monogamous relationship for at least 1 year prior to screening and with whom he intends to remain in a relationship for the duration of the study;
  9. Normal reproductive state as demonstrated by:

    • Sperm concentration ≥15 million/mL in two semen samples and with no gross abnormalities of sperm motility and morphology on at least one semen sample assessment;
    • Screening Testosterone within the study site's local lab normal reference range for adult men;
  10. Willingness to accept a low but unknown risk of conceiving a pregnancy for the duration of the trial.

Female participant - Inclusion Criteria

Women who meet all the following criteria will be eligible for enrollment in the trial:

  1. Good general health with no chronic medical conditions that result in periodic exacerbations which require significant medical care or are known to affect fertility;
  2. Aged between 18 and 34 years, inclusive, at the enrollment visit;
  3. Have regular menstrual cycles of 21-35 days in duration, per patient report, when not using hormonal contraception. If hormonal contraception has been used, the following applies:

    1. If recently used intramuscular Depo-Provera must have had last injection at least 3 months prior enrollment;
    2. If using an IUD or an implant, she is planning to have this removed for purposes unrelated to enrollment in the study prior to entering the efficacy phase;
    3. Completion of her last pack of oral contraceptives or completion of effectiveness period for a monthly injection, patch or ring if any has been used prior to entering the efficacy phase;
  4. Have intact uterus and both ovaries (waivers for women who have one ovary may be submitted so that the circumstances related to prior ovarian removal can be assessed);
  5. The subject is legally competent, has been informed of the nature, the scope and the relevance of the study, voluntarily agrees to participation and the study's provisions and has duly signed the informed consent form (ICF);
  6. Consistent use of effective contraception during the preceding cycle prior to enrolling;
  7. No known infertility;
  8. Intends to remain in a monogamous relationship with male study partner (as specified above). (Note: this study will not provide her contraception for intercourse with any other male partners);
  9. Be at risk for pregnancy with participating male partner (heterosexual vaginal intercourse at least once per cycle and not sterilized);
  10. Have a negative pregnancy test at enrollment;
  11. Willingness to accept a low but unknown risk of pregnancy and able to understand the need for follow-up in case of pregnancy;
  12. No medical contraindication to pregnancy;

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 (or within five half-lives of the investigational drug, whichever is longer) prior to the first screening visit.
  2. Men not living in the catchment's area of the study site or within a reasonable distance from the site.
  3. Clinically significant abnormal findings at screening per the Investigator's medical judgment.
  4. Elevated PSA levels ≥ 4 ng/mL.
  5. Abnormal serum chemistry values that may indicate clinically significant liver or kidney dysfunction.
  6. Use of androgens or other anabolic steroids that may suppress gonadotropins within 6 months prior to the first screening visit.
  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 used to determine eligibility).
  8. History of hypertension, including hypertension controlled with treatment.
  9. Known history of primary testicular disease or disorders of the hypothalamic-pituitary axis.
  10. Known hypersensitivity to progestins or testosterone or any excipient of the investigational product.
  11. History of prostate, testicular or breast carcinoma.
  12. Significant prostatic symptoms (IPSS > 15).
  13. Known history of reproductive dysfunction including vasectomy or infertility.
  14. Known history of significant cardiac, renal, hepatic or prostatic disease.
  15. History of thromboembolic disease.
  16. A serious systemic disease such as diabetes mellitus (including diabetes controlled with treatment), HIV, or morbid obesity.
  17. Current active or ongoing Hepatitis infection.
  18. History of untreated sleep apnea.
  19. 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.
  20. Any known active or chronic dermatitis or other severe skin disorder.
  21. Any skin condition that might interfere with absorption of gel.
  22. Couples desiring fertility within the study participation period (approximately 104 weeks from screening to end of recovery).
  23. PHQ9 score ≥15 or history of severe depression or other serious mental health disorder, including ongoing use of an anti-depressant.
  24. Men participating in competitive sports where drug screening for prohibited substances (including anabolic steroids) is routine. Exclusion is due to the potential of testing positive for androgens that may occur from their study participation coupled with the unknown efficacy (i.e. duration of positive testing) of a single application.
  25. Use of sex steroids or medications which might interfere with steroid metabolism (i.e. ketoconazole, finasteride, oral corticosteroids, dutasteride and statins).
  26. Use of anticoagulants.
  27. Use of medications that will interfere or interact with Nestorone or Testosterone.
  28. Use of oily cosmetic skin gels/products that would prevent absorption of steroids.
  29. Previous participation in this clinical trial.
  30. Any site staff member with delegated study responsibilities or a family member of a site staff member with delegated study responsibilities.

Female participant - Exclusion Criteria

  1. Desire to become pregnant during the study.
  2. Breastfeeding.
  3. Known or suspected current alcoholism or drug abuse.
  4. Participation in another clinical trial involving an investigational drug within the last 30 days prior to the first screening visit.
  5. Currently pregnant.
  6. Known hypersensitivity to progestins or testosterone.
  7. History associated with impaired fertility (e.g. history of pelvic inflammatory disease, unilateral salpingectomy or endometriosis).
  8. Previous participation in this clinical trial.
  9. Any site staff member with delegated study responsibilities or a family member of a site staff member with delegated study responsibilities.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Listed Location Countries  ICMJE Chile,   Italy,   Kenya,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03452111
Other Study ID Numbers  ICMJE CCN017
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Health Decisions
Study Sponsor  ICMJE Health Decisions
Collaborators  ICMJE
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • Population Council
Investigators  ICMJE Not Provided
PRS Account Health Decisions
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP