ContraceptionPhase 1NES-1NCT00229593
NES Gel-1, To Evaluate Nestorone Gel in Combination With Testosterone Gel
A Phase 1 study testing Nestorone gel and Testosterone Gel in people with Contraception, run by University of Washington at 2 sites in United States.
Trial summary
The purpose of this study is to determine the usefulness of two transdermal gels to be used in the future development for a male contraceptive. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception
- What is being tested?
- Nestorone gel and Testosterone Gel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2005to Jan 2007
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy men
- Aged 18-50 years
- With normal clinical chemistry, serum levels of testosterone, PSA, gonadotropins within normal limits, and sperm concentration greater than 20 million/mL
- Subject or his partner willing to use a recognized effective method of contraception
Who cannot join
- Men not living in area of clinics
- Clinically significant abnormal findings at screening
- Elevated PSA greater than 4
- Partners who are pregnant
- Abnormal laboratory values, liver or kidney dysfunction
- Sperm counts below 20 million/mL.
Show all 18Show fewer
- Use of androgens or body building substances within 6 months of enrollment,
- Blood pressure greater than 140/90, history of hypertension, including hypertension controlled with treatment
- History of primary testicular disease or disorder of the hypothalamic-pituitary axis
- Hypersensitivity of progestins
- History of venous thromboembolism
- Benign or malignant liver tumors
- Active liver disease, history of reproductive dysfunction including vasectomy or infertility
- History of active or chronic cardiac, renal, hepatic or prostatic disease
- Diabetes mellitus or morbid obesity (body weight greater than 120% of ideal body weight)
- Known or suspected alcoholism or drug abuse
- Known dermatitis or severe skin disorder
- Men desiring fertility within 6 months or 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 fertility or sporting status.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Washington Medical Center
Seattle, Washington, 98195
Harbor-UCLA Medical Center
Torrance, California, 90509
About this study
Official title: A Randomized, Open Label Clinical Trial to Evaluate if Nestorone Gel Has Gonadotropin Suppressive Activity and if Nestorone in Combination With Testosterone Will Have an Additive Effect on Gonadotropin Suppression When Applied Transdermally in Healthy Men
The purpose of this study is to determine the usefulness of two transdermal gels to be used in the future development for a male contraceptive.
Read the detailed description
The success of hormonal male contraception depends on the near complete suppression of spermatogenesis without producing any untoward effects on libido or other androgen-dependent functions or any other adverse events. The treatment with androgen alone has geen shown to be highly effective in Asian men but less effective in non-Asian men in clinical trials. To increase the efficacy of androgen alone treatment on spermatogenesis, combined regimens of a progestin and an androgen have shown promising results. The steady-state delivery of a progestin and an androgen by transdermal gel application would be a user-friendly delivery method as compared to injectable or implant approaches. Nestorone (NES) is a synthetic progestin that does not have any androgenic and estrogenic activity and is not expected to have some of the undesirable side effects of other drugs.
We propose to evaluate whether NES gel alone or in combination with T gel applied transdermally will result in more effective suppression of gonadotropins than NES or T gel applied alone in healthy men. Fifty healthy male subjects, age 18-50 will be enrolled at each center (2 sites).
- Conditions
- Contraception
- Being tested
- Nestorone gel, Testosterone Gel
- Keywords
- Male contraception, Androgen, Progestin, Spermatogenesis, Gonadotropin suppression, Testosterone, Nestorone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nestorone gelDrug
2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment
Testosterone GelDrug
Also called Testim
100 mg Testosterone gel daily for 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | 100 mg Testosterone gel daily for 3 weeks Receives: Drug: Testosterone Gel |
| 2 | Active comparator | 2 mg Nestorone gel daily for 3 weeks Receives: Drug: Nestorone gel |
| 3 | Active comparator | 4 mg Nestorone gel daily for 3 weeks Receives: Drug: Nestorone gel |
| 4 | Active comparator | 100 mg Testosterone gel + 2 mg Nestorone gel Receives: Drug: Nestorone gel; Drug: Testosterone Gel |
| 5 | Active comparator | 100 mg Testosterone gel + 4 mg Nestorone gel Receives: Drug: Nestorone gel; Drug: Testosterone Gel |
| 6 | Active comparator | 100 mg Testosterone Gel + 6 mg Nestorone Gel daily for 3 weeks Receives: Drug: Nestorone gel; Drug: Testosterone Gel |
| 7 | Active comparator | 100 mg Testosterone Gel + 8 mg Nestorone gel daily for 3 weeks Receives: Drug: Nestorone gel; Drug: Testosterone Gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
- To determine the gonadotropin suppressive activity of Nestorone (NES) Gel at two doses and T gel at one dose alone or in combination over a 3-week period. Serum levels of gonadotropins will be assessed in all subjects.
Measured: 3 weeks
Secondary outcomes (2)
To determine the effects on serum levels of total and free testosterone and SHBG and measure serum levels of NES gel.
Measured: 3 weeks
Safety measured laboratory evaluations, vitals, pre- and post treatment physical exam results and PSA levels
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2005 (estimated)
- Study startSep 2005
- Primary completionJan 2007
- Study completionJan 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, William Bremner, University of Washington
- Investigators
- William J Bremner, MD, PhD, Principal investigator, University of WashingtonChristina Wang, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00229593
- Sponsor's protocol ID
- 26852-D
- Other IDs
- HHSN27500002;, 04-3792-D 02
- Acronym
- NES-1
- Status last verified
- Dec 2014
- First submitted
- 27 Sep 2005
- Last updated
- 4 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Anawalt BD, Bebb RA, Bremner WJ, Matsumoto AM. A lower dosage levonorgestrel and testosterone combination effectively suppresses spermatogenesis and circulating gonadotropin levels with fewer metabolic effects than higher dosage combinations. J Androl. 1999 May-Jun;20(3):407-14.
PubMed 10386821Anderson RA, Kinniburgh D, Baird DT. Suppression of spermatogenesis by etonogestrel implants with depot testosterone: potential for long-acting male contraception. J Clin Endocrinol Metab. 2002 Aug;87(8):3640-9. doi: 10.1210/jcem.87.8.8773.
PubMed 12161488Bebb RA, Anawalt BD, Christensen RB, Paulsen CA, Bremner WJ, Matsumoto AM. Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach. J Clin Endocrinol Metab. 1996 Feb;81(2):757-62. doi: 10.1210/jcem.81.2.8636300.
PubMed 8636300Brache V, Massai R, Mishell DR, Moo-Young AJ, Alvarez F, Salvatierra AM, Cochon L, Croxatto H, Robbins A, Faundes A. Ovarian function during use of Nestorone(R) subdermal implants. Contraception. 2000 Mar;61(3):199-204. doi: 10.1016/s0010-7824(00)00092-5.
PubMed 10827334Cummings DE, Bremner WJ. Prospects for new hormonal male contraceptives. Endocrinol Metab Clin North Am. 1994 Dec;23(4):893-922.
PubMed 7705326Diaz S, Schiappacasse V, Pavez M, Zepeda A, Moo-Young AJ, Brandeis A, Lahteenmaki P, Croxatto HB. Clinical trial with Nestorone subdermal contraceptive implants. Contraception. 1995 Jan;51(1):33-8. doi: 10.1016/0010-7824(94)00006-i.
PubMed 7750282Gonzalo IT, Swerdloff RS, Nelson AL, Clevenger B, Garcia R, Berman N, Wang C. Levonorgestrel implants (Norplant II) for male contraception clinical trials: combination with transdermal and injectable testosterone. J Clin Endocrinol Metab. 2002 Aug;87(8):3562-72. doi: 10.1210/jcem.87.8.8710.
PubMed 12161475Haukkamaa M, Laurikka-Routti M, Heikinheimo O, Moo-Young A. Contraception with subdermal implants releasing the progestin ST-1435: a dose-finding study. Contraception. 1992 Jan;45(1):49-55. doi: 10.1016/0010-7824(92)90140-o.
PubMed 1591921Handelsman DJ, Conway AJ, Howe CJ, Turner L, Mackey MA. Establishing the minimum effective dose and additive effects of depot progestin in suppression of human spermatogenesis by a testosterone depot. J Clin Endocrinol Metab. 1996 Nov;81(11):4113-21. doi: 10.1210/jcem.81.11.8923869.
PubMed 8923869Kamischke A, Heuermann T, Kruger K, von Eckardstein S, Schellschmidt I, Rubig A, Nieschlag E. An effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations. J Clin Endocrinol Metab. 2002 Feb;87(2):530-9. doi: 10.1210/jcem.87.2.8218.
PubMed 11836281Kamischke A, Venherm S, Ploger D, von Eckardstein S, Nieschlag E. Intramuscular testosterone undecanoate and norethisterone enanthate in a clinical trial for male contraception. J Clin Endocrinol Metab. 2001 Jan;86(1):303-9. doi: 10.1210/jcem.86.1.7057.
PubMed 11232016Mahabadi V, Amory JK, Swerdloff RS, Bremner WJ, Page ST, Sitruk-Ware R, Christensen PD, Kumar N, Tsong YY, Blithe D, Wang C. Combined transdermal testosterone gel and the progestin nestorone suppresses serum gonadotropins in men. J Clin Endocrinol Metab. 2009 Jul;94(7):2313-20. doi: 10.1210/jc.2008-2604. Epub 2009 Apr 14.
PubMed 19366848
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open Label Clinical Trial to Evaluate if Nestorone Gel Has Gonadotropin Suppressive Activity and if Nestorone in Combination With Testosterone Will Have an Additive Effect on Gonadotropin Suppression When Applied Transdermally in Healthy Men
- ClinicalTrials.gov ID
- NCT00229593
- Acronym / sponsor ID
- NES-1 / 26852-D
- Conditions
- Contraception
- Keywords
- Male contraception, Androgen, Progestin, Spermatogenesis, Gonadotropin suppression, Testosterone, Nestorone
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Sep 2005
- Primary completion
- Jan 2007 (actual)
- Study completion
- Jan 2007 (actual)
- First posted
- 29 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the usefulness of two transdermal gels to be used in the future development for a male contraceptive.
Detailed description
The success of hormonal male contraception depends on the near complete suppression of spermatogenesis without producing any untoward effects on libido or other androgen-dependent functions or any other adverse events. The treatment with androgen alone has geen shown to be highly effective in Asian men but less effective in non-Asian men in clinical trials. To increase the efficacy of androgen alone treatment on spermatogenesis, combined regimens of a progestin and an androgen have shown promising results. The steady-state delivery of a progestin and an androgen by transdermal gel application would be a user-friendly delivery method as compared to injectable or implant approaches. Nestorone (NES) is a synthetic progestin that does not have any androgenic and estrogenic activity and is not expected to have some of the undesirable side effects of other drugs.
We propose to evaluate whether NES gel alone or in combination with T gel applied transdermally will result in more effective suppression of gonadotropins than NES or T gel applied alone in healthy men. Fifty healthy male subjects, age 18-50 will be enrolled at each center (2 sites).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Testosterone Gel100 mg Testosterone gel daily for 3 weeks |
| 2 | Active comparator | Drug: Nestorone gel2 mg Nestorone gel daily for 3 weeks |
| 3 | Active comparator | Drug: Nestorone gel4 mg Nestorone gel daily for 3 weeks |
| 4 | Active comparator | Drug: Nestorone gel, Drug: Testosterone Gel100 mg Testosterone gel + 2 mg Nestorone gel |
| 5 | Active comparator | Drug: Nestorone gel, Drug: Testosterone Gel100 mg Testosterone gel + 4 mg Nestorone gel |
| 6 | Active comparator | Drug: Nestorone gel, Drug: Testosterone Gel100 mg Testosterone Gel + 6 mg Nestorone Gel daily for 3 weeks |
| 7 | Active comparator | Drug: Nestorone gel, Drug: Testosterone Gel100 mg Testosterone Gel + 8 mg Nestorone gel daily for 3 weeks |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy men
- Aged 18-50 years
- With normal clinical chemistry, serum levels of testosterone, PSA, gonadotropins within normal limits, and sperm concentration greater than 20 million/mL
- Subject or his partner willing to use a recognized effective method of contraception
Key exclusion criteria (18 listed)
- Men not living in area of clinics
- Clinically significant abnormal findings at screening
- Elevated PSA greater than 4
- Partners who are pregnant
- Abnormal laboratory values, liver or kidney dysfunction
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nestorone gel2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment | Drug | 2, 3, 4, 5, 6, 7 |
| Testosterone GelAlso: Testim100 mg Testosterone gel daily for 3 weeks | Drug | 1, 4, 5, 6, 7 |
Primary outcome
- To determine the gonadotropin suppressive activity of Nestorone (NES) Gel at two doses and T gel at one dose alone or in combination over a 3-week period. Serum levels of gonadotropins will be assessed in all subjects.
Time frame: 3 weeks
2 secondary outcomes
To determine the effects on serum levels of total and free testosterone and SHBG and measure serum levels of NES gel.
Time frame: 3 weeks
Safety measured laboratory evaluations, vitals, pre- and post treatment physical exam results and PSA levels
Time frame: 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2014.
- Background: PubMed 10386821Anawalt BD, Bebb RA, Bremner WJ, Matsumoto AM. A lower dosage levonorgestrel and testosterone combination effectively suppresses spermatogenesis and circulating gonadotropin levels with fewer metabolic effects than higher dosage combinations. J Androl. 1999 May-Jun;20(3):407-14.
- Background: PubMed 12161488Anderson RA, Kinniburgh D, Baird DT. Suppression of spermatogenesis by etonogestrel implants with depot testosterone: potential for long-acting male contraception. J Clin Endocrinol Metab. 2002 Aug;87(8):3640-9. doi: 10.1210/jcem.87.8.8773.
- Background: PubMed 8636300Bebb RA, Anawalt BD, Christensen RB, Paulsen CA, Bremner WJ, Matsumoto AM. Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach. J Clin Endocrinol Metab. 1996 Feb;81(2):757-62. doi: 10.1210/jcem.81.2.8636300.
- Background: PubMed 10827334Brache V, Massai R, Mishell DR, Moo-Young AJ, Alvarez F, Salvatierra AM, Cochon L, Croxatto H, Robbins A, Faundes A. Ovarian function during use of Nestorone(R) subdermal implants. Contraception. 2000 Mar;61(3):199-204. doi: 10.1016/s0010-7824(00)00092-5.
- Background: PubMed 7705326Cummings DE, Bremner WJ. Prospects for new hormonal male contraceptives. Endocrinol Metab Clin North Am. 1994 Dec;23(4):893-922.
- Background: PubMed 7750282Diaz S, Schiappacasse V, Pavez M, Zepeda A, Moo-Young AJ, Brandeis A, Lahteenmaki P, Croxatto HB. Clinical trial with Nestorone subdermal contraceptive implants. Contraception. 1995 Jan;51(1):33-8. doi: 10.1016/0010-7824(94)00006-i.
- Background: PubMed 12161475Gonzalo IT, Swerdloff RS, Nelson AL, Clevenger B, Garcia R, Berman N, Wang C. Levonorgestrel implants (Norplant II) for male contraception clinical trials: combination with transdermal and injectable testosterone. J Clin Endocrinol Metab. 2002 Aug;87(8):3562-72. doi: 10.1210/jcem.87.8.8710.
- Background: PubMed 1591921Haukkamaa M, Laurikka-Routti M, Heikinheimo O, Moo-Young A. Contraception with subdermal implants releasing the progestin ST-1435: a dose-finding study. Contraception. 1992 Jan;45(1):49-55. doi: 10.1016/0010-7824(92)90140-o.
- Background: PubMed 8923869Handelsman DJ, Conway AJ, Howe CJ, Turner L, Mackey MA. Establishing the minimum effective dose and additive effects of depot progestin in suppression of human spermatogenesis by a testosterone depot. J Clin Endocrinol Metab. 1996 Nov;81(11):4113-21. doi: 10.1210/jcem.81.11.8923869.
- Background: PubMed 11836281Kamischke A, Heuermann T, Kruger K, von Eckardstein S, Schellschmidt I, Rubig A, Nieschlag E. An effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations. J Clin Endocrinol Metab. 2002 Feb;87(2):530-9. doi: 10.1210/jcem.87.2.8218.
- Background: PubMed 11232016Kamischke A, Venherm S, Ploger D, von Eckardstein S, Nieschlag E. Intramuscular testosterone undecanoate and norethisterone enanthate in a clinical trial for male contraception. J Clin Endocrinol Metab. 2001 Jan;86(1):303-9. doi: 10.1210/jcem.86.1.7057.
- Results publication: PubMed 19366848Mahabadi V, Amory JK, Swerdloff RS, Bremner WJ, Page ST, Sitruk-Ware R, Christensen PD, Kumar N, Tsong YY, Blithe D, Wang C. Combined transdermal testosterone gel and the progestin nestorone suppresses serum gonadotropins in men. J Clin Endocrinol Metab. 2009 Jul;94(7):2313-20. doi: 10.1210/jc.2008-2604. Epub 2009 Apr 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William J Bremner, MD, PhD principal investigator
University of Washington
Christina Wang, MD principal investigator
University of California, Los Angeles
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nestorone gel and Testosterone Gel in people with Contraception, run by University of Washington at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
- To determine the gonadotropin suppressive activity of Nestorone (NES) Gel at two doses and T gel at one dose alone or in combination over a 3-week period. Serum levels of gonadotropins will be assessed in all subjects. (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00229593, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2014.