Seven hundred thirty two (732) patients were treated with cetrorelix acetate for injection in five (two Phase 2 dose-finding and three Phase 3) clinical trials. The clinical trial population consisted of Caucasians (95.5%) and Black, Asian, Arabian and others (4.5%). Women were between 19 and 40 years of age (mean: 32). The studies excluded subjects with polycystic ovary syndrome (PCOS), subjects with low or no ovarian reserve, and subjects with stage III-IV endometriosis.

Two dose regimens were investigated in these clinical trials, either a single dose per treatment cycle or multiple dosing. In the Phase 2 studies, a single dose of 3 mg was established as the minimal effective dose for the inhibition of premature LH surges with a protection period of at least 4 days. When cetrorelix acetate for injection is administered in a multidose regimen, 0.25 mg was established as the minimal effective dose. The extent and duration of LH-suppression is dose dependent.

In the Phase 3 program, efficacy of the single 3 mg dose regimen of cetrorelix acetate for injection and the multiple 0.25 mg dose regimen of cetrorelix acetate for injection was established separately in two adequate and well controlled clinical studies utilizing active comparators. A third non-comparative clinical study evaluated only the multiple 0.25 mg dose regimen of cetrorelix acetate for injection. The ovarian stimulation treatment with recombinant FSH or human menopausal gonadotropin (hMG) was initiated on day 2 or 3 of a normal menstrual cycle. The dose of gonadotropins was administered according to the individual patient's disposition and response.

In the single dose regimen study, cetrorelix acetate for injection 3 mg was administered on the day of controlled ovarian stimulation when adequate estradiol levels (400 pg/mL) were obtained, usually on day 7 (range day 5-12). If hCG was not given within 4 days of the 3 mg dose of cetrorelix acetate for injection, then 0.25 mg of cetrorelix acetate for injection was administered daily beginning 96 hours after the 3 mg injection until and including the day of hCG administration.

In the two multiple dose regimen studies, cetrorelix acetate for injection 0.25 mg was started on day 5 or 6 of COS. Both gonadotropins and cetrorelix acetate for injection were continued daily (multiple dose regimen) until the injection of human chorionic gonadotropin (hCG).

Oocyte pick-up (OPU) followed by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) as well as embryo transfer (ET) were subsequently performed. The results for cetrorelix acetate for injection are summarized below in Table 2.

In addition to IVF and ICSI, one pregnancy was obtained after intrauterine insemination. In the five Phase 2 and Phase 3 clinical trials, 184 pregnancies have been reported out of a total of 732 patients (including 21 pregnancies following the replacement of frozen-thawed embryos).

In the 3 mg regimen, 9 patients received an additional dose of 0.25 mg of cetrorelix acetate for injection and two other patients received two additional doses of 0.25 mg cetrorelix acetate for injection. The median number of days of cetrorelix acetate for injection multiple dose treatment was 5 (range 1-15) in both studies.

No drug related allergic reactions were reported from these clinical studies.