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

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)]

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).

Study Overview

• Status: Completed
• Conditions: Luteal Hormone Supplementation
• Intervention / Treatment: Drug: FE 999913 vaginal tablet

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan
    • IVF Namba Clinic
  • Tokyo, Japan
    • Sanno Hospital
  • Hyogo
    • Kobe, Hyogo, Japan
      • Hanabusa Women's Clinic
  • Kanagawa
    • Ebina, Kanagawa, Japan
      • Ebina Ladies Clinic
    • Sagamihara, Kanagawa, Japan
      • Sophia Ladies Clinic
    • Yokohama, Kanagawa, Japan
      • Bashamichi Ladies Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 42 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: FE 999913 100 mg BID; FE 999913 100 mg vaginal tablet BID	Drug: FE 999913 vaginal tablet
ACTIVE_COMPARATOR: FE 999913 100 mg TID; FE 999913 100 mg vaginal tablet TID	Drug: FE 999913 vaginal tablet

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Publications and helpful links

General Publications

• Fujiwara T. A multi-center, randomized, open-label, parallel group study of a natural micronized progesterone vaginal tablet as a luteal support agent in Japanese women undergoing assisted reproductive technology. Reprod Med Biol. 2015;14(4):185-193. doi: 10.1007/s12522-015-0211-y. Epub 2015 Jun 14.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (ACTUAL): August 1, 2013
• Study Completion (ACTUAL): August 1, 2013

Study Registration Dates

• First Submitted: October 9, 2012
• First Submitted That Met QC Criteria: October 17, 2012
• First Posted (ESTIMATE): October 19, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): September 5, 2014
• Last Update Submitted That Met QC Criteria: August 29, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: 000072