A Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg Daily Versus Crinone 8% Intravaginal Progesterone Gel 90 mg Daily for Luteal Support in In-Vitro Fertilization (LOTUS II)

Study Overview
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Brief Summary
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The purpose of this randomized, two-arm and open label study is to demonstrate that the treatment of a daily dose of 3x10mg dydrogesterone orally is as effective and safe as the daily dose Crinone 8% intravaginal progesterone gel 90 mg for the luteal support in women who are unable to conceive a child and are 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 during treatment until 30 days after delivery to record any safety and tolerability data of the patient and their newborn (s).

Detailed Description
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This article has been accepted for publication in Human Reproduction published by Oxford University Press.

Official Title
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A Randomized, Open-label, Two-arm, Multicenter Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg Daily Versus Crinone 8% Intravaginal Progesterone Gel 90 mg Daily for Luteal Support in In-Vitro Fertilization (LOTUS II)

Conditions
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Female Infertility

Intervention / Treatment
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* Drug: Dydrogesterone 30 mg
* Drug: intravaginal progesterone gel 90 mg


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 screening 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 at screening 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 or at 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 prior 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) Subject is not pregnant , confirmed by negative pregnancy or by Investigator Judgement 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, 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; Acute urogenital disease Known allergic reactions to progesterone products Known allergic reactions to peanuts and peanut oil Intake of àny experimental drug or any 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 Acute urogenital disease

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dydrogesterone tablets 3x10 mg<br>Dydrogesterone tablets 3x10 mg | Drug: Dydrogesterone 30 mg<br>* Oral Dydrogesterone 10 mg tablets tid<br>|
| Experimental: Crinone 8% intravaginal progesterone gel 90 mg<br>Crinone 8% intravaginal progesterone gel 90 mg | Drug: intravaginal progesterone gel 90 mg<br> <br> * Other names: Crinone 8% intravaginal progesterone gel 90 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Presence of Fetal Heart Beats at 12 Week's Gestation Determined by Transvaginal Ultrasound | Pregnancy rate defined as the presence of fetal heart beats at 12 weeks' gestation determined by transvaginal ultrasound. | 12 weeks´ gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive Pregnancy Test Rate (Percentage of Participants With a Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer) | Positive biochemical pregnancy test on Day 14 after embryo transfer | Day 14 after embryo transfer | 
| Rate of Successful Completion of Pregnancy (Percentage of Participants With a Live Birth) | Live birth rate (percentage of participants with a live birth) | After delivery (about 9 months after IVF) | 
| Physical Examination Newborn (Number of Delivered Newborns That Are Male or Female) | The gender (number of delivered newborns that are male or female) | After delivery (about 9 months after IVF) |