Japanese Bridging Trial of Org 37462 (Study P05969)(COMPLETED)

A Phase II Bridging Trial of Org 37462

The purpose of this study is to find the optimal dose of Org 37462 for Japanese females undergoing controlled ovarian stimulation for in vitro fertilization intracytoplasmic sperm injection (IVF-ICSI).

Inclusion Criteria:

• Japanese females of infertile married couples with an indication for COH and IVF with or without ICSI.

• At least 20 but not older than 39 years of age at the time of screening.

• A body mass index (BMI) between 18 and 29.

• Normal menstrual cycle with a range of 24-35 days and an intra-individual variation of plus or minus 3 days (but never outside the 24-35 days range).

• Infertile couple that is willing to give written informed consent.

• Determination of inclusion criteria

  • is determined in view of the planned therapeutic indication.
  • is determined based on ethical considerations for the subjects (not younger than 20) and also in view of the planned therapeutic indication (not older than 39)
  • is determined to avoid bias on the effects of Org 37462 by emaciation and obesity.
  • is determined to avoid the influences of endogenous hormones considering the purpose of this trial to select the minimal effective dose of Org 37462.
  • is determined from the ethical consideration of the subjects.

Exclusion Criteria:

• History of/or current endocrine abnormality such as polycystic ovary syndrome (PCOS) or polycystic ovaries according to USS, (treated) hyperprolactinemia or evidence of ovarian dysfunction.

• History of non- or low- ovarian response to FSH/hMG treatment.

• Abnormal cervical smear according to the Papanicolaou (>= class III) or Bethesda (>= CIN 1) scale.

• History of/or current Type I hypersensitivity (urticaria, eczema, hay fever, asthma), meaning that the subject is using prescribed medication on a regular basis or that the subjects history is prohibitive for Org 37462 treatment according to the clinical opinion of the sub-investigator.

• Any hormone value outside the reference range during the early follicular phase as measured by the central laboratory (Japan) [FSH, LH, E2, P, androstenedione (AD), dehydroepiandrosterone sulphate (DHEAS), testosterone (T), thyroid stimulating hormone (TSH) and prolactin].

• Any clinically significant abnormal laboratory value of the central laboratory (Japan) (routine hematology, blood biochemistry).

• Any ovarian and/or abdominal abnormality that would interfere with adequate ultrasound investigation of both ovaries, thus excluding subjects with only one ovary.

• Contra-indications for the use of gonadotropins i.e.,

  • tumors of ovary, breast, uterus, pituitary or hypothalamus.
  • pregnancy or lactation.
  • undiagnosed vaginal bleeding.
  • hypersensitivity to any of the substances in recFSH (FSH, sucrose, sodium citrate, polysorbate 20 and sodium chloride, L-methionine).
  • ovarian cysts or enlarged ovaries not related to PCOS.
  • malformation of the sexual organs incompatible with pregnancy.
  • fibroid tumors of the uterus incompatible with pregnancy.

• Use of hormonal preparations within 1 month prior to screening.

• Hypertension (systolic blood pressure >150 mm Hg and/or diastolic blood pressure >90 mm Hg) or treated hypertension.

• Epilepsia, diabetes, cardiovascular, gastro-intestinal, hepatic, renal, pulmonary, or abdominal disease.

• Administration of investigational drugs within 3 months prior to screening.