A Multicenter Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg Daily Versus Intravaginal Micronized Progesterone Capsules 600 mg Daily for Luteal Support in In-Vitro Fertilization

Study Overview
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Brief Summary
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Female inability to conceive a child. The purpose of this randomized, two-arm and double blind, double dummy study is to demonstrate that the treatment of a daily dose of 3x10mg dydrogesterone orally is as effective and safe as the daily dose of 3x200 mg micronized progesterone capsules administered intravaginally for the luteal support in patients undergoing IVF. The treatment will start on the day of oocyte retrieval and continue until pregnancy is negative or until week 12 gestation.Patients will be followed after treatment until 30 days after delivery to record any safety and tolerability data of the patient and their newborn(s).

Official Title
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A Double-Blind, Double-Dummy, Randomized, Two-arm, Multicenter Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg Daily Versus Intravaginal Micronized Progesterone Capsules 600 mg Daily for Luteal Support in In-Vitro Fertilization (Lotus I)

Conditions
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Female Infertility

Intervention / Treatment
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* Drug: Dydrogesterone 30 mg
* Drug: Micronized Progesterone 600 mg
* Drug: Placebo progesterone
* Drug: Placebo dydrogesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Premenopausal females, age > 18 years < 42 years Non-smokers. For females who were past smokers, they must have stopped tobacco usage for at least 3 months prior baseline visit Early follicular phase (Day 2-4) Follicle stimulating hormone (FSH) less than or equal to 15 IU/L and estradiol (E2)within normal limits Luteinizing hormone (LH), prolactin (PRL), T (testosterone) and thyroid-stimulating hormone (TSH), within the normal limits for the clinical laboratory, or considered not clinically significant by the Investigator within 6 months prior to screening 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) Normal transvaginal ultrasound at screening (or within 14 days of screening) without evidence of clinically significant abnormality consistent with finding adequate for Assisted Reproductive Technology (ART) with respect to uterus and adnexa (no hydrosalpinx or clinically relevant uterine fibroids) Negative pregnancy test on the day of pituitary down regulation (prior to administration of gonadotropin releasing hormones (GnRH) agonist or GnRH antagonist) Clinically indicated protocol for induction of IVF with a fresh embryo Single or dual embryo transfer BMI ≥ 18 and ≤ 30 kg/m2 Exclusion Criteria: Evidence of cardiovascular, respiratory, urogenital, gastrointestinal/hepatic, hematologic/immunologic, head, ears, eyes, nose, throat (HEENT), 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 Acute urogenital disease Known allergic reactions to progesterone products Known allergic reactions to peanuts and peanut oil Intake of experimental drug or participation in any other clinical trial within 30 days prior to study start Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subjects to participate in or to complete the study 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) History of chemotherapy or radiotherapy Patients with more than 3 unsuccessful IVF attempts Contraindication for pregnancy Refusal or inability to comply with the requirements of the study protocol for any reason, including scheduled clinic visits and laboratory tests History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 41 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dydrogesterone 30 mg<br> | Drug: Dydrogesterone 30 mg<br>* Oral Dydrogesterone 10 mg tablets tid<br>Drug: Placebo progesterone<br>* Placebo intravaginal micronized progesterone 200 mg capsules tid<br>|
| Experimental: Micronized Progesterone 600 mg<br> | Drug: Micronized Progesterone 600 mg<br>* Intravaginal micronized progesterone 200 mg capsules tid<br>Drug: Placebo dydrogesterone<br>* placebo oral dydrogesterone 10 mg tablets tid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Being Pregnant as Measured by the Presence of Fetal Heart Beats at 12 Weeks´Gestation Using Transvaginal Ultrasound | Percentage of participants being pregnant as measured by the presence of fetal heart beats at 12 weeks´gestation using transvaginal ultrasound | 12 weeks´ gestation (at visit 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Being Pregnant as Measured by the Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer | Percentage of participants being pregnant as measured by the positive biochemical pregnancy test on Day 14 after embryo transfer | Day 14 after embryo transfer | 
| Percentage of Participants With a Successful Completion of Pregnancy | Incidence of live births and healthy newborns | After delivery (about 9 months after IVF) | 
| Gender of the Newborn | was recorded and collected for Newborn | After delivery (about 9 months after IVF) |