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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003540 |
E.1.2 | Term | Assisted fertilization |
E.1.2 | System Organ Class | 100000004865 |
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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 |
The primary objective is to demonstrate non-inferiority of oral dydrogesterone 10 mg TID versus micronized progesterone vaginal capsules 200 mg TID. The primary efficacy parameter is the presence of fetal heart beats at 12 weeks’ gestation determined by transvaginal ultrasound. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives and parameters are a positive pregnancy test on Day 14 after embryo transfer, the incidence of live births and healthy newborns.
The safety objective is to obtain safety and tolerability data by means of documentation of treatment emergent adverse events (TEAE) during the entire study period. In addition, data on vital signs, physical examination findings, and routine laboratory values will be obtained. Furthermore, signs and symptoms of threatened abortion, the rate of hypospadias and the rate of masculinization in female babies will be recorded. The time of delivery (pregnancy week) and the following parameters of the newborn will be obtained at delivery: gender, APGAR Score, weight, height, head circumference, abnormal findings of physical examination and any malformations. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent;
2. Premenopausal females, age > 18 years < 42 years
3. Non-smokers. For females who were past smokers, they must have stopped tobacco usage for at least 3 months prior baseline visit
4. Early follicular phase (Day 2-4) FSH (Follicle stimulating hormone) less than or equal to 15 IU/L and estradiol (E2)within normal limits
5. LH (luteinizing hormone), PRL (prolactin), T (testosterone) and TSH (thyroid-stimulating hormone), within the normal limits for the clinical laboratory, or considered not clinically significant by the Investigator within 6 months prior to screening
6. Documented history of infertility (e.g., unable to conceive for at least one year or for 6 months for women ≥ 38 years of age or bilateral tubal occlusion or absence)
7. Normal transvaginal ultrasound at screening (or within 14 days of screening) without evidence of clinically significant abnormality consistent with finding adequate for ART with respect to uterus and adnexa (no hydrosalpinx or clinically relevant uterine fibroids)
8. Negative pregnancy test on the day of pituitary down regulation (prior to administration of GnRH agonist or GnRH antagonist)
9. Clinically indicated protocol for induction of IVF with a fresh embryo
10. Single or dual embryo transfer
11. BMI ≥ 18 and ≤ 30 kg/m2
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E.4 | Principal exclusion criteria |
1. 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;
2. Acute urogenital disease
3. Known allergic reactions to progesterone products
4. Known allergic reactions to peanuts and peanut oil
5. Intake of experimental drug or participation in any other clinical trial within 30 days prior to study start
6. Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subjects to participate in or to complete the study
7. Current or recent substance abuse, including alcohol and tobacco (Note: Patients who stopped tobacco usage at least 3 months prior to screening visit would be allowed)
8. History of chemotherapy or radiotherapy
9. Patients with more than 3 unsuccessful IVF attempts
10. Contraindication for pregnancy
11. Refusal or inability to comply with the requirements of the study protocol for any reason, including scheduled clinic visits and laboratory tests
12. History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy parameter is the pregnancy rate defined as the presence of fetal heart beats at 12 weeks’ gestation determined by transvaginal ultrasound.
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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) |
The secondary parameters are a positive pregnancy test on Day 14 after embryo transfer, the incidence of live births and healthy newborns.
Further secondary parameters are gender and APGAR score as well as the height, weight and head circumference of the newborn (s).
In addition, a physical examination of the newborn will be performed and any malformations will be recorded.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 14 after embryo transfer and birth
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.4 | Double blind | Yes |
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 | No |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | No |
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 |
Austria |
Belgium |
India |
Israel |
Russian Federation |
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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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End of Study is defined as Last Subject Last Visit |
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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 | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |