A Phase III Study of FE 999913 in Japanese Female Patients Undergoing Fertility Treatment

Study Overview
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Brief Summary
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The purposes of the study are to verify sufficient supplementation of luteal hormone after administrating FE999913 Vaginal Tablet twice a day (BID) or three times a day (TID) and to determine the efficacy and safety of FE999913 Vaginal Tablet in Japanese women undergoing fertility treatment with IVF-ET (a fresh embryo transfer).

Official Title
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A Multi-Center, Randomized, Open-Label, Parallel Group Study of FE 999913 Vaginal Tablet 100 mg in Japanese Female Patients Undergoing Fertility Treatment [In Vitro Fertilization/Embryo Transfer (IVF-ET)]

Conditions
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Luteal Hormone Supplementation

Intervention / Treatment
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* Drug: FE 999913 vaginal tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-menopausal adult women between the ages of 20 and 42 years. Early follicular phase (day 2-4) follicle stimulating hormone (FSH) ≤12 IU/L and Estradiol <100 pg/mL. Luteinizing hormone (LH), prolactin (PRL), and thyroid-stimulating hormone (TSH), within the normal limits for the clinical laboratory tests, 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]. Transvaginal ultrasound at screening (or within 14 days prior to screening) consistent with findings adequate for Assisted Reproduction Technology (ART) with respect to uterus and adnexa (peripheral reproductive organs). At least one cycle with no fertility medication prior to screening. Hysterosalpingography, hysteroscopy, sonohysterogram, or transvaginal ultrasound documenting a normal uterine cavity. Consent to contraception during the cycle in which pituitary down regulation is performed (prior to start of controlled ovarian stimulation). Signed informed consent to fertility treatment using FE999913 Vaginal Tablet after the subject and her husband have thoroughly understood the content. Exclusion Criteria: Donor oocyte or embryo recipient; gestational or surrogate carrier. Undergoing blastomer biopsy and other experimental ART procedures. Severe hepatic dysfunction or disease. Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events. Porphyria. Presence of any clinically relevant systemic disease (eg, insulin-dependent diabetes mellitus). Past or current surgical or medical condition which in the judgment of the Principal Investigator (or Sub-investigator) may interfere with absorption, distribution, metabolism, or excretion of the study drug. Subjects with a body mass index (BMI) of >34 at time of Screening. Previous IVF or ART failure due to a poor response to gonadotropins*. * Defined as development of ≤2 mature follicles or history of 2 previous cycle cancellations prior to oocyte retrieval due to poor response. Presence of abnormal uterine bleeding of undetermined origin. Current or recent (within the past 12 months) substance abuse, including alcohol. Known or suspected breast or genital tract cancer. History of chemotherapy or radiotherapy for malignant disorder (chorionic disease). Currently breast feeding, pregnant or contraindication to pregnancy. Refusal or inability to comply with the requirements of the Protocol for any reason, including scheduled visits and clinical laboratory tests. Documented intolerance or allergy to any of the medications to be used in the study including the investigational medicinal product. Participation in any experimental drug study within 60 days prior to Screening. Use of any of the following medications during the pretreatment and treatment phase: hormonal drug products (use of oral contraceptives prior to start of controlled ovarian stimulation is allowed), other progesterone drug products, hydrocortisone and other steroid drug products, and fertility modifiers such as insulin sensitizers. History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 42 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 |
| --- | --- |
| Active Comparator: FE 999913 100 mg BID<br>FE 999913 100 mg vaginal tablet BID | Drug: FE 999913 vaginal tablet<br> <br> |
| Active Comparator: FE 999913 100 mg TID<br>FE 999913 100 mg vaginal tablet TID | Drug: FE 999913 vaginal tablet<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Subjects With Blood Progesterone Concentration Not Less Than 10 ng/ml |  | Day 5 of treatment | 
| Ongoing Pregnancy Rate | Defined as identification of fetal survival and fetal heart movements on transvaginal ultrasound | Week 5 of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Positive βeta Human Chorionic Gonadotrophin (βhCG) |  | Week 2 of study | 
| Clinical Pregnancy Rate | Defined as presence of a gestational sac on transvaginal ultrasound | Week 4 of study | 
| Blood Progesterone Concentration |  | Weeks 2, 4, 5, 8, and end of study |