A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Fertinex Pharmacology, Pharmacokinetics, Studies, Metabolism - Urofollitropin
Fertinex Pharmacology, Pharmacokinetics, Studies, Metabolism - Urofollitropin
CLINICAL PHARMACOLOGY
FertinexTM (urofollitropin for injection, purified) stimulates
ovarian follicular growth in women who do not have primary ovarian failure.
FSH, the active component of FertinexTM is the primary hormone
responsible for follicular recruitment and development. In order to effect
final maturation of the follicle and ovulation in the absence of an endogenous
LH surge, human chorionic gonadotropin (hCG) must be given following the
administration of FertinexTM when monitoring of the patient
indicates that sufficient follicular development has occurred. There may
be a degree of interpatient variability in response to FSH administration.
Pharmacokinetics
In a comparative, single-dose, double-blind, double-dummy, randomized,
cross-over study, FertinexTM administered subcutaneously demonstrated
a similar pharmacokinetic profile to urofollitropin and FertinexTM
administered intramuscularly. No significant differences were found between
the treatment groups in AUC/dose and CMAX/dose parameters. A variability
in TMAX was observed. Subcutaneous administration of FertinexTM
led to a slower absorption rate resulting in a later TMAX (15 ± 7h) than
following IM administration of either FertinexTM (10 ± 4h)
or urofollitropin (9 ± 4h).
Plasma inhibin levels were measured as a pharmacodynamic marker of FSH
activity. The inhibin concentration-time profile of inhibin following
FertinexTM administered subcutaneously was found to be similar
to that following urofollitropin and FertinexTM administered
intramuscularly.
Special Populations
Safety and efficacy of FertinexTM in renal or hepatic insufficiency
have not been established.
Drug-Drug Interactions
No clinically significant drug-drug interactions have been reported (see
PRECAUTIONS).
CLINICAL STUDIES
Ovulation Induction
The safety and efficacy of FertinexTM administered subcutaneously
vs. urofollitropin administered intramuscularly for ovulation induction
was assessed in a phase III, open-label, randomized, comparative, multicenter
study in oligo-ovulatory infertile women who failed to ovulate or conceive
following adequate clomiphene citrate therapy. The purpose of the study
was to demonstrate that FertinexTM a highly purified follicle
stimulating hormone (FSH) administered subcutaneously, is clinically not
different in terms of safety and efficacy from urofollitropin administered
intramuscularly. The principal efficacy parameters recorded were serum
estradiol levels, follicular growth, ovulation rate and pregnancy rate.
Two hundred eleven patients entered treatment, of whom 108 received FertinexTM
and 103 received urofollitropin. Overall, two-hundred and four patients
(491 cycles) were considered evaluable. There were no differences between
the FertinexTM administered subcutaneously and the urofollitropin
intramuscular treatment groups in serum estradiol levels and follicular
growth (follicle number and size) on the day of human chorionic gonadotropin
(hCG) administration, nor were there any differences between the treatment
groups in ovulation rates or pregnancy rates per patient.
The results of safety and efficacy with FertinexTM administered
subcutaneously for ovulation induction in oligo-ovulatory infertile women
are summarized below:
Cumulative Patient Ovulation Rates
The cumulative patient ovulation rate by cycle is presented for the 102
evaluable patients with documentation of ovulatory status in at least
one cycle :
| Cycle 1 |
|
83% |
| Cycle 2 |
|
97% |
| Cycle 3 |
|
100% |
Cumulative Patient Pregnancy Rates
The cumulative patient pregnancy rate by cycle is presented for 86 evaluable
patients who received hCG :
| Cycle 1 |
|
14% |
| Cycle 2 |
|
21% |
| Cycle 3 |
|
29% |
| Patients Aborting* |
|
8% |
| Multiple Births* |
|
21% |
| Severe Hyperstimulation Syndrome |
|
0% |
* Based upon 25 evaluable clinical pregnancies
** Based upon 108 patients and 266 cycles evaluable for safety
Assisted Reproductive Technologies (ART)
The safety and efficacy of FertinexTM administered subcutaneously
for Assisted Reproductive Technologies (ART) were assessed in a phase
III, multicenter, non-comparative, clinical trial in ovulatory infertile
women undergoing stimulation of multiple follicular development for In
Vitro Fertilization and Embryo Transfer (IVF/ET) after pituitary down-regulation
with a GnRH agonist. The initial and maximal doses of FertinexTM
were 225 and 450 IU, respectively, The principal parameters recorded were
serum estradiol on day of hCG administration, the number and maturity
of retrieved oocytes, drug therapy and duration, and clinical pregnancy
rate per initiated cycle and per retrieval. One hundred and thirty-nine
patients were enrolled in the study; 135 patients were treated with FertinexTM
and 122 patients were considered evaluable for efficacy. The results listed
below represent mean data of 118 evaluable patients who received hCG in
the 10 study centers:
| Total number of oocytes recovered |
|
8.4 |
| Mature oocytes recovered |
|
5.9 |
| Maximum serum E2, day hCG (pg/mL) |
|
1682 |
| Total number of ampules (75 IU) |
|
36 |
| Treatment duration (days) |
|
11.5 |
| Clinical pregnancy attempt |
|
23% (0-60)*
|
| Clinical pregnancy transfer |
|
27% (0-60)*
|
* reflects range across centers
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