Clinical trial efficacy in OI and ART¹

Study design

Seven hundred thirty-two (732) patients were treated with Cetrotide^® (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 Cetrotide^® 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 Cetrotide^®* and the multiple 0.25 mg dose regimen of Cetrotide^® was established separately in 2 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 Cetrotide^®. 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, Cetrotide^® 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 Cetrotide^®, then 0.25 mg of Cetrotide^® 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, Cetrotide^® 0.25 mg was started on day 5 or 6 of COS. Both gonadotropins and Cetrotide^® 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 Cetrotide^® are summarized below.

Results with Cetrotide^®

^a_Progesterone 

^b_{Following initiation of Cetrotide^®  therapy} 

^c_{Morning values}

^d_{Median with 5th – 95th percentiles} 

^e_{Mean ± standard deviation}

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).