E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Spermatogenesis suppression for male contraception |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065589 |
E.1.2 | Term | Male contraception |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
With the goal to develop a therapeutic regime of contraception in the male: to measure the rate of suppression of spermatogenesis induced in healthy male volunteers by a combination of Norethisterone Enantate and Testosterone Undecanoate administered every 8 weeks for up to 3 injection visits. Moreover to measure the level of contraceptive protection provided by the continued administration of NET-EN and TU every 8 weeks for an efficacy period of up to 56 weeks. |
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E.2.2 | Secondary objectives of the trial |
1. Maintenance of suppression of spermatogenesis below the threshold criterion for contraception by the combined regimen, throughout the Efficacy Phase; 2. Reversibility of the regimen as determined by the return of semen concentrations to at least 20 million/ml or to a level generally considered fertile as defined by current WHO recommendations; 3. Alterations in circulating concentrations of steroid and peptide hormones as a result of administration of this regimen; 4. Safety, as monitored by reports of symptoms, examination findings, urine, and blood tests; and 5. Hormonal regimen (method) acceptability. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for male volunteers Signed written Consent Form Ages 18-45 years Normal reproductive state demonstrated by sperm concentrations and screening gonadotropin and testosterone levels Body Mass Index (BMI) between 20 and 32 kg/m² Sexually active with female partner, with a coital frequency of 2/week, on average In a stable mutually monogamous relationship/partnership with the female partner for at least 1 year and intends to remain in the relationship for the course of the study No desire for partner pregnancy within the next 2 years and willing to accept a low but unknown risk of pregnancy. Inclusion criteria for the female partners Signed written Consent Form Female healthy subjects Ages 18-35 years, inclusive No tubal ligation Sexually active with male volunteer, with a coital frequency of 2/week, on average Normal reproductive state In a stable mutually monogamous relationship/partnership with the male volunteer for at least 1 year and intends to remain in the relationship for the course of the study Not pregnant at the time of entry to the Suppression Phase No desire for pregnancy within the next 2 years and willing to accept a low but unknown risk of pregnancy. |
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E.4 | Principal exclusion criteria |
Exclusion criteria for the male volunteers: History of prostate or testicular pathology or male infertility Diseases (including tumors) that may be affected by testosterone use or that may affect the outcome of the study Use of any disallowed medications as listed in the Investigators Brochure or of any drug known to affect absorption, distribution, metabolism or excretion (ADME) of testosterone within the 30 days preceding the first administration of the test compounds Use of oral anticoagulatory drugs (e.g., warfarin) within the 30 days preceding the first administration of the test compounds and during the study Implantation of a sustained-action sex hormone within 8 months of Visit A Exclusion criteria for the female partners: Participation in any other clinical trial that would affect fertility Use of DMPA 12 months prior to Visit A |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. The proportion of male participants who are rendered azoospermic and/or severely oligozoospermic (sperm concentrations < 1 million/ml) at any point in the Suppression Phase; 2. 12-month contraceptive method failure rates. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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1) il regime terapeutico non sopprime la spermatogenesi ad un livello minore uguale ad 1 milione/ml nel 90% dei soggetti entro le 24 settimane della fase di soppressione; 2) si ha un tasso di gravidanze o di eventi avversi superiore al concesso |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |