Clinical trials
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®
| Parameter |
|
Cetrotide® 0.25 mg (md, active comparator study) |
Cetrotide® 0.25 mg (md, non-comparative study) |
| No. of subjects |
159 | 303 | |
| hCG administered [%] | 96.2 |
96.0 | |
| Oocyte pick-up [%] | 94.3 |
93.1 |
|
| LH-surge [%] (LH ≥ 10 U/L and Pa ≥ 1 ng/mL)b |
1.9 |
1.0 |
|
| Serum E2 [pg/ml] at day hCGc,d |
1064 (341-2531) |
1185 (311-3676) |
|
| Serum LH [U/L] at day hCGc,d |
1.5 (0.5-7.6) |
1.1 (0.5-3.5) |
|
| No. of follicles ≥ 11 mm at day hCGe |
10.8±5.2 | 10.4±4.5 | |
| No. of oocytes: IVFe_ ICSIe |
7.6±4.3 10.1±5.6 |
8.5±5.1 9.3±5.9 |
|
| Fertilization rate: IVFe |
0.62±0.26 | 0.60±0.26 |
aProgesterone
bFollowing initiation of Cetrotide® therapy
cMorning values
dMedian with 5th – 95th percentiles
eMean ± 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).
