Investigate Dose of Org 36286 to Initiate Multiple Follicular Growth in a Controlled Ovarian Hyperstimulation Protocol for IVF or IVF/ICSI (P07015)
Condition: Infertility; In Vitro Fertilization
MeSH terms: Infertility
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary objective of this trial was to investigate the appropriate dose of a single
      injection of Org 36286 to initiate multifollicular growth for the first seven days in a
      controlled ovarian hyperstimulation (COH) protocol for IVF and IVF/ICSI. After seven days,
      participants were converted to treatment with Puregon® 150 IU and administration of the GnRH
      antagonist Orgalutran® to finalize the stimulation cycle. Secondary objectives were the
      safety (including the absence of antibody formation) and the direct effects of Org 36286 on
      reproductive functions (steroidogenesis, oocyte maturation, embryo quality and implantation).
    

Detailed description: 
      This trial was made up of two stages with different designs and was conducted at two clinical
      trial sites. Stage I was open-label and uncontrolled in a small cohort of women (n=6) to
      obtain first experience in employing Org 36286 in women meeting all inclusion and none of the
      exclusion criteria. Based on the results of a previous study, the most appropriate dose was
      anticipated to be 120 μg Org 36286, which was administered on Cycle Day 2 or 3. After seven
      days, treatment was continued with a fixed dose of 150 IU Puregon® SC. If the size of the
      leading follicle was >=14 mm, 0.25 mg Orgalutran® SC once daily was administered concurrently
      with 150 IU Puregon® up to and including the day of hCG. The maximum total treatment duration
      was 19 days. Treatment of the first two participants with Org 36286 120 μg, that was expected
      to be adequate for COH, was cancelled due to disrupted follicular growth beyond Day 7.
      Therefore, the dose of Org 36286 was adapted from 120 μg to 180 µg. Treatment of the first
      participants gave an indication of the validity of the anticipated doses to be used in Stage
      II, the actual dose-finding trial. Stage II was open-label, prospective and randomized,
      comparing three experimental regimens differing in dose of Org 36286 (120 μg, 180 μg, or 240
      μg) with a reference treatment. Post-treatment assessments were completed at the visit two
      weeks after embryo transfer.
    

Intervention name(s): Org 36286; Puregon®; Orgalutran®; Pregnyl®
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Intra-abdominal injection of Org 36286; Subcutaneous Puregon® 150 IU; Subcutaneous Orgalutran® 0.25 mg; Subcutaneous Pregnyl® 10,000 IU
Other intervention name(s): Corifollitropin alpha; recFSH; ganirelix (Ganirelix Acetate Injection); human chorionic gonadatropin; hCG
Intervention MeSH terms: Chorionic Gonadotropin; Ganirelix
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pharmacological effects of drugs; Hormones; Hormone substitutes and Hormone Antagonists; Pharmacological Actions; Randomized; Multi-center; Multi-national