Study of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception

NCT03452111 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: CCN017
• Study Type: interventional
• Target: 420
• Locations: 7 countries
• Sites: 17

Brief Summary

The long term objective is to develop a gel to be used as a male contraceptive.

Conditions

Healthy; Men; Male Contraception

Keywords

Healthy Men; Couple; Gel; Male Contraception; Nestorone; Testosterone

Outcome Measures

Primary Outcomes (1)

• Contraceptive efficacy provided by daily application of NES/T gel for 52 wks during the efficacy phase of the study determined using Kaplan-Meier methods to estimate the 12-mth cumulative pregnancy probability in the efficacy(evaluable cycles)population.

  12 months

Secondary Outcomes (26)

• 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.

  20 weeks

• Maintenance of suppression of spermatogensis 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 52 week efficacy phase of the study.

  52 weeks

• Changes from baseline in Follicle Stimulating Hormone (FSH) with daily use of the NES/T gel.

  24 months

• Changes from baseline in Luteinizing Hormone (LH) with daily use of the NES/T gel.

  24 months

• Changes from baseline in Sex Hormone Binding Globulin (SHBG) with daily use of the NES/T gel.

  24 months

Study Arms (1)

Nestorone (NES) + testosterone (T) combined gel

EXPERIMENTAL

A combination Gel with Nestorone® (NES) and Testosterone (T) applied transdermally (NES/T gel). 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 or 74 mg of T of which 6.2 mg of T with the original dose (Cohort A) and about 7.4mg of T with the second dose (Cohort B) will be absorbed per day (10% skin absorption)

Drug: Nestorone + Testosterone Combination Gel

Interventions

Nestorone + Testosterone Combination Gel DRUG

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. 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.

Also known as: NES/T gel

Nestorone (NES) + testosterone (T) combined gel

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• to 50 years of age, at the enrollment visit;
• BMI \< 33 kg/m2;
• No history of androgen use in the six months prior to the first screening visit;
• 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 the first 7 days of the recovery phase and then only use the experimental method during the efficacy phase of the study;
• In the opinion of the investigator, the male subject is willing and able to comply with the protocol, understand and sign an informed consent and HIPAA form;
• 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);
• 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;
• No known infertility;
• 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;
• Willingness to accept a low but unknown risk of conceiving a pregnancy for the duration of the trial.
• Women who meet all the following criteria will be eligible for enrollment in the trial:

You may not qualify if:

• 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 (or within five half-lives of the investigational drug, whichever is longer) prior to the first screening visit.
• Men not living in the catchment's area of the study site or within a reasonable distance from the site.
• Clinically significant abnormal findings at screening per the Investigator's medical judgment.
• Elevated PSA levels ≥ 4 ng/mL.
• Abnormal serum chemistry values that may indicate clinically significant liver or kidney dysfunction.
• Use of androgens or other anabolic steroids that may suppress gonadotropins within 6 months prior to the first screening visit.
• 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 2 measurements will be used to determine eligibility).
• History of hypertension, including hypertension controlled with treatment.
• Known history of primary testicular disease or disorders of the hypothalamic-pituitary axis.
• Known hypersensitivity to progestins or testosterone or any excipient of the investigational product.
• History of prostate, testicular or breast carcinoma.
• Significant prostatic symptoms (IPSS \> 15).
• Known history of reproductive dysfunction including vasectomy or infertility.
• Known history of significant cardiac, renal, hepatic or prostatic disease.

Sponsors & Collaborators

• Premier Research: lead
• Population Council: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (17)

UC Davis Health

Sacramento, California, 95817, United States

Location

The Lunquist Institute at Harbor-UCLA Medical Center

Torrance, California, 90509, United States

Location

Comprehensive Women's Health Center

Denver, Colorado, 80230, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Eastern Virginia Medical School-EVMS Obstetrics & Gynecology

Norfolk, Virginia, 23507, United States

Location

University of Washington Medical Center & Health Sciences

Seattle, Washington, 98195, United States

Location

Centro de Medicina Reproductiva Shady Grove Chile

Santiago, Vitacura, 7650672, Chile

Location

Chilean Institute of Reproductive Medicine

Santiago, 8320000, Chile

Location

University of Bologna, Italy

Bologna, 40138, Italy

Location

Kenyatta National Hospital

Nairobi, 00202, Kenya

Location

Karolinska Institutet

Stockholm, Sweden

Location

University of Edinburgh

Edinburgh, EH 16 4SA, United Kingdom

Location

University of Manchester, UK

Manchester, M13 9WL, United Kingdom

Location

Spilhaus Clinical Research Site

Harare, 00000, Zimbabwe

Location

Related Publications (1)

• Lue Y, Swerdloff R, Pak Y, Nguyen BT, Yuen F, Liu PY, Blithe DL, Wang C. Male contraception development: monitoring effective spermatogenesis suppression utilizing a user-controlled sperm concentration test compared with standard semen analysis. Fertil Steril. 2023 Feb;119(2):208-217. doi: 10.1016/j.fertnstert.2022.11.002. Epub 2022 Nov 5.

  PMID: 36347310 DERIVED

MeSH Terms

Conditions

Multiple Endocrine Neoplasia Type 1

Interventions

ST 1435

Condition Hierarchy (Ancestors)

Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Study Officials

• Diana Blithe, PhD

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Program Director, NICHD

Study Record Dates

• First Submitted: February 23, 2018
• First Posted: March 2, 2018
• Study Start: October 25, 2018
• Primary Completion: September 6, 2024
• Study Completion: September 6, 2024
• Last Updated: February 18, 2025

Record last verified: 2025-02

Locations

KE (1); SE (1); IT (1); CL (2); GB (2); ZI (1); US (9)