E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Female inability to conceive a child |
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E.1.1.2 | Therapeutic area | Body processes [G] - Reproductive physiologi cal processes [G08] |
MedDRA Classification |
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 |
The primary objective is to study the difference of oral dydrogesterone (Duphaston®) versus micronized vaginal progesterone (Utrogestan®) as luteal phase support after controlled ovarian stimulation on the molecular endometrial level (using Illumina RNA-seq, immunohistochemistry and flow cytometry on endometrial derived single cell suspensions). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: • to study the pharmacokinetics after OD versus MVP intake as LPS after COS (using LC-MS/MS [Liquid Chromatography with tandem Mass Spectrometry]) • to study the effects of OD versus MVP on the peripheral immunology (using flow cytometry to investigate T regulatory and T effector cells derived from peripheral blood) • to study the difference in microbiota in the female genital tract after OD versus MVP as LPS after COS (using 16S rRNA amplicon sequencing - Illumina miSeq) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age >18 years and <35 years 2. Oocyte donor candidates 3. Regularly cycling 4. BMI ≥18 and ≤ 29 kg/m2 5. Signed informed consent 6. Non-smokers. 7. AMH <7,53 and >1,18 ng/mL (90th and 10th percentile for healthy women aged 25-29 according to the used Elecsys® AMH kit by Roche) 8. PRL, T and TSH within the normal limits for the clinical laboratory, or considered not clinically significant by the investigator within 6 months prior or at screening |
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E.4 | Principal exclusion criteria |
1. Intra-uterine device 2. Previous enrollment 3. Evidence of cardiovascular, respiratory, urogenital, gastrointestinal/hepatic, hematologic/immunologic, HEENT (head, ears, eyes, nose, throat), dermatologic/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurologic/psychiatric, allergy, recent major surgery (< 3 months), or other relevant diseases as revealed by history, physical examination and/or laboratory assessments which could limit participation in or completion of the study 4. Acute urogenital disease during the course of the study 5. Known allergic reactions to progesterone / dydrogesterone products (active substance or to any of the excipients) 6. Intake of any experimental drug or any participation in any other clinical trial within 30 days prior to study start. 7. Mental disability or any other lack of fitness, in the investigator's opinion, to preclude subjects in or to complete the study. 8. Current or recent substance abuse, including alcohol and tobacco (patients who stopped tobacco usage at least 3 months prior to screening visit would be allowed) 9. Refusal or inability to comply with the requirements of the study protocol for any reason, including scheduled clinic visits and laboratory tests. 10. Known or suspected progestogen dependent neoplasms (e.g. meningioma) 11. Serum progesterone level >1.5 ng/mL at ovulation triggering |
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E.5 End points |
E.5.1 | Primary end point(s) |
The difference of oral dydrogesterone versus micronized vaginal progesterone as luteal phase support after controlled ovarian stimulation on the molecular endometrial level |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
On the eight day of luteal phase support intake after oocyte retrieval in the first and second cycle.
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E.5.2 | Secondary end point(s) |
• The pharmacokinetics after oral dydrogesterone versus micronized vaginal progesterone as luteal phase support after controlled ovarian stimulation • The effects of oral dydrogesterone versus micronized vaginal progesterone on the peripheral immunology • The difference in microbiota in the female genital tract after oral dydrogesterone versus micronized vaginal progesterone as luteal phase support after controlled ovarian stimulation
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pharmacokinetics, peripheral immunology, microbiota: on the first and eight day of the luteal phase support intake after oocyte retrieval in the first and second cycle. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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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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 | |
E.8.9.1 | In the Member State concerned days | |