Male contraception Pregnancy and Childbirth Male contraception
Conditions
Interventions
Interventions as of 24/09/2007:
Study participants will receive the following:
Norethisterone enantate (NET-EN) 200 mg and testosterone undecanoate (TU) 1000 mg injecti
Sponsors
UNDP/UNFPA/WHO/World Bank - Special Programme of Research, Development and Research Training in Human Reproduction (HRP)
CONRAD (USA)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Amended 13/08/2010: Male participants: 3.1. Sperm concentration greater than or equal to 15 million sperm/ml semen or total sperm count greater than or equal to 39 million sperm per ejaculate in two semen samples, with no gross abnormalities of sperm motility and morphology, per investigator's discretion 3.2. Screening gonadotropin (LH and FSH) and testosterone levels should be within the centre's normal ranges, however gonadotropin levels may fall below the lower limit of the normal ranges assuming the overall endocrine profile and semen parameters are indicative of a normal reproductive state Female partners: 3. Age 18 to 39 years, inclusive All other inclusion criteria remain the same. Current information as of 24/09/2007: Male participants: 1. Signed written consent form 2. Male healthy volunteer 3. Normal reproductive state demonstrated by: 3.1. Sperm concentrations greater than or equal to 20 million sperm/ml semen in two semen samples with no gross abnormalities if sperm motility and morphology per investigator's discretion 3.2. Screening gonadotropin and testosterone levels within the centre's normal ranges 4. Body mass index between 20 and 32 kg/m^2 5. History and clinical examination without pathological findings relevant to the study including symptoms or signs of a sexually transmitted infection 6. Digital rectal examination of the prostate does not reveal any abnormal findings and prostate specific antigen (PSA) level is within normal range 7. Laboratory assays do not suggest the presence of any illness 8. Sexually active with female partner, with a coital frequency of twice a week, on average 9. In a stable, mutually monogamous relationship/partnership with the female partner for at least one year within first visit and intends to remain in the relationship for the course of the study 10. Willing to comply with the requirements of the protocol 11. No desire for partner pregnancy within the next two years and willing to accept a low but unknown risk of pregnancy Female partners: 1. Signed written consent form 2. Female healthy volunteer 3. Age 18 to 35 years, inclusive 4. No tubal ligation 5. Sexually active with male volunteer, with a coital frequency of twice a week, on average 6. Normal reproductive state, demonstrated by: 6.1. Regular menstrual cycles (23 - 38 days) by volunteer history for the past three months 6.2. Medical and gynaecological history without findings suggestive of impaired fertility 6.3. No contraindication to pregnancy 6.4. No signs or symptoms of a sexually transmitted infection 7. In a stable mutually monogamous relationship/partnership with the male volunteer for at least one year and intends to remain in the relationship for the course of the study 8. Willing to comply with the requirements of the study protocol 9. Not pregnant at the time of entry into the Suppression phase 10. No desire for pregnancy within the
Exclusion criteria
Exclusion criteria: Amended 13/08/2010: Male participants: 4. History of or current prostate or testicular pathology (including varicocele that is visible or palpable without Valsalva maneuver) or male infertility. All other exclusion criteria remain the same. Added 24/09/2007: Male participants: 1. Participation in another clinical trial within 30 days preceding the first drug administration, or simultaneous participation in another clinical trial 2. Institutionalised or imprisoned by order of the court 3. Competition in sports which use World Anti-Doping Agency (WADA) monitoring 4. History of prostate or testicular pathology or male infertility 5. Serious organic or psychiatric disease suspected from history and.or clinical examination 6. Diseases (including tumours) that may be affected by testosterone use or that may affect the outcome of the study, for example: 6.1. Prostate disease 6.2. Past or present history, or family history, of thrombotic or embolic diseases 6.3. Hypertension requiring therapy (blood pressure [BP] greater than or equal to 140/190 mmHg) 6.4. Acute or chronic hepatic diseases 6.5. Manifest renal diseases with renal dysfunction 7. Biochemical and/or haematological laboratory values outside normal ranges, unless the investigator confirms that the deviations are of no clinical revelance 8. Any indication of chronic use of illicit drugs or alcohol abuse 9. Use of any disallowed medications or of any drug known to affect absorption, distribution, metabolism or elimination (ADME) of testosterone within the 30 days preceding the first administration of the test compounds 10. Use of oral anti-coagulatory drugs (e.g. warfarin) within the 30 days preceding the first administration of the test compounds and during the study (aspirin is allowed) 11. Implantation of a sustained-action sex hormone within 8 months of screening 12. History of allergy to any component of the study drugs Female partners: 1. Participation in any other clinical trial that would affect fertility 2. Use of depot medroxyprogesterone acetate (DMPA) 12 months prior to screening 3. Any indication of chronic use of illicit drugs or alcohol abuse
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The proportion of male participants who are rendered azoospermic and/or severely oligozoospermic (sperm concentrations less than or equal to 1 million/ml) at any point in the Suppression Phase 2. 12-month contraceptive method failure rates. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of men who remain azoospermic and/or severely oligozoospermic (sperm concentrations less than or equal to 1 million/ml) throughout the Efficacy Phase 2. Average length of time that men remain azoospermic and/or severely oligozoospermic (sperm concentrations less than or equal to 1 million/ml) in the Efficacy Phase 3. Proportion of men who recover, as defined in the protocol, within 12 months after their last “missed” injection 4. Average length of time to recovery among all men who enter the Efficacy Phase 5. Changes in steroid and peptide hormone levels compared with baseline 6. Reports of adverse events, overall and product-related 7. Changes in key physical findings, endocrinology levels, serum chemistries, urinalysis, hematology tests and PSA levels at study end compared with baseline 8. Answers to key questions on acceptability questionnaires | — |
Countries
Australia, Chile, Germany, India, Indonesia, Italy, United Kingdom
Outcome results
None listed