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)
Condition: Female Infertility
MeSH terms: Infertility; Infertility, Female
Intervention: Dydrogesterone 30 mg; intravaginal progesterone gel 90 mg
Intervention description: Oral Dydrogesterone 10 mg tablets tid
Intervention MeSH terms: Progesterone; Dydrogesterone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1034.0
Sex: Female
Minimum age: 19 Years
Maximum age: 41 Years
Healthy volunteers: No

Summary:

      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).
    

Eligibility criteria:

        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