E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation for assisted reproductive technologies (ART) |
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E.1.1.1 | Medical condition in easily understood language |
Mujeres donantes de óvulos para ciclos de reproducción asistida |
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E.1.1.2 | Therapeutic area | Body processes [G] - Reproductive physiologi cal processes [G08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021926 |
E.1.2 | Term | Infertility |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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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 |
? To evaluate the synchrony of the follicle cohort at the start of stimulation associated with a mid-luteal injection of degarelix compared to placebo ? To describe the endometrial receptivity associated with the degarelix regimens (degarelix starting in the mid-luteal phase or degarelix starting in the early follicular phase) in comparison to the fixed gonadotrophin releasing hormone (GnRH) antagonist protocol, during controlled ovarian hyperstimulation with luteal support |
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E.2.2 | Secondary objectives of the trial |
? To describe the ovarian / follicular development as well as the number of cumulus-oocyte complexes associated with the degarelix regimens in comparison to the fixed GnRH antagonist protocol ? To describe the circulating concentrations of selected endocrine parameters during treatment with the degarelix regimens in comparison to the fixed GnRH antagonist protocol ? To describe the treatment efficiency of the degarelix regimens in comparison to the fixed GnRH antagonist protocol ? To explore the pharmacokinetics of degarelix ? To establish the safety profile of the degarelix regimens in comparison to the fixed GnRH antagonist protocol |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed Informed Consent Form, prior to screening evaluations 2. In good physical and mental health 3. Pre-menopausal females between the ages of 18-35 years (both inclusive) at the time of randomisation 4. Regular menstrual cycles of 26-35 days duration (both inclusive), presumed to be ovulatory 5. Body mass index (BMI) between 18 and 29 kg/m2 (both inclusive) 6. Transvaginal ultrasound documenting presence and adequate visualization of the uterus without obvious structural abnormalities which could compromise endometrial biopsy sampling (results obtained within 12 months prior to randomisation) 7. Transvaginal ultrasound documenting presence and adequate visualization of both ovaries, without evidence of abnormality (e.g., no endometrioma of 3 cm or greater), and normal adnexa (e.g., no hydrosalpinx) (results obtained within 6 months prior to randomisation) 8. Early follicular phase serum levels of FSH within normal limits (1-12 IU/L) (results obtained within 12 months prior to randomisation) 9. Early follicular phase antral follicle (2-10 mm) count ? 10 on cycle day 3 (±1 d) of the screening cycle 10. Willing to donate the retrieved oocytes 11. Willing to use an adequate barrier method of contraception from informed consent to Day hCG injection +7 and to use an adequate barrier or hormonal method of contraception from Day hCG injection +7 to the end-of-study visit |
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E.4 | Principal exclusion criteria |
1. Abnormal karyotype 2. Any known clinically significant systemic disease (e.g., insulin dependent diabetes) 3. Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) which can compromise participation in the study 4. Diagnosed with polycystic ovarian syndrome or endometriosis stage III / IV 5. Diagnosed as ?poor responder?, defined as a) > 20 days of gonadotrophin stimulation in a previous COH cycle, or b) Any previous cancellation of a COH cycle due to limited follicular response, or c) Development of less than 4 follicles ? 15 mm in a previous COH cycle 6. History of recurrent miscarriage (defined as three consecutive spontaneous losses before weeks 24 of pregnancy) 7. Severe OHSS in a previous COH cycle 8. Undiagnosed vaginal bleeding 9. Pregnancy or lactation 10. Tumours of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus 11. Any concomitant medications that would interfere with evaluation of study medications. Specifically, any non-study hormonal therapy (except for thyroid medication), anti-psychotics (ATC code N05A), anti-depressants (ATC code N06), anxiolytics (ATC code N05B), hypnotics and sedatives (ATC code N05C) or continuous use of prostaglandin inhibitors (non-steroid anti-inflammatory drugs (NSAIDs), including aspirin) within 2 weeks prior to randomisation 12. Current or past (12 months prior to randomisation) abuse of alcohol or drugs, and/or current (last month) use of alcohol (more than 14 units per week) 13. Current or past (3 months prior to randomisation) smoking habit of more than 20 cigarettes per day 14. History of chemotherapy (except for gestational conditions) or radiotherapy 15. Use of any investigational drug during 3 months prior to start of the current COH cycle 16. Previous participation in the study 17. Hypersensitivity to any trial product |
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E.5 End points |
E.5.1 | Primary end point(s) |
? Coefficient of variation of follicular sizes on Stimulation Day 1 (follicles ? 2 mm) ? Frequency of oocyte donors with adequate secretory transformation at the endometrial histology evaluation on Day hCG injection +7 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Describir el desarrollo ovárico / folicular, así como el número de complejos oocitos-cumulus asociados a los regímenes de degarelix en comparación con el protocolo fijo de antagonistas de GnRH |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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The end-of-study visit takes place 12 weeks (±2 weeks) after oocyte retrieval. As post-study follow-up, data on fertilised oocytes / embryos, positive ?hCG test, clinical and ongoing pregnancy as well as pregnancy outcome (delivery outcome and neonatal health, including live birth) will be collected. In addition, data from the frozen embryo replacement cycles conducted within 6 months after freezing will be collected. The post-study follow-up data will be reported separately. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |