Clinical trial NCT01185704: Analysis of Two Therapeutic With Cetrotide® in Polycystic Ovarian (PCO) Women in Assisted Reproductive Technology (ART)
Official title: A Phase IIIb Randomized Open-label Study to Compare the Estradiol Level on the Releasing Day in Two Regimen of Cetrotide® 0.25 mg Used From Day 1 or From Day 7 of the Menstrual Cycle (Day 0 or Day 6 of Stimulation) in Polycystic Ovarian (PCO) Women in ART (IVF/ICSI).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Polycystic Ovarian Syndrome
Keywords: Cetrorelix acetate; follitropin alfa; human chorionic-gonadotropin alfa; follicular maturation; pregnancy; ovarian stimulation
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
Collaborators: name: Merck Serono S.A.S, France
First posted: 2010-08-20
Enrollment: 136
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized open-label study to compare between in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes of the two regimen of Cetrotide® (Cetrorelix acetate) which are 0.25 milligram (mg) used from Day 1 or Day 7 of the menstrual cycle (Day 0 or Day 6 of stimulation) in polycystic ovarian (PCO) women in assisted reproductive technology (ART).

Detailed description: Polycystic ovarian syndrome population is an androgenic syndrome characterized by a wide spectrum of clinical manifestations such as obesity, hirsutism, insulin resistance, diabetes and presence of specific ultrasonic features.

Cetrotide®, cetrorelix acetate, is an antagonist of luteinizing-hormone-releasing hormone (LHRH). Cetrotide® is registered in 70 countries (including France) for the prevention of premature ovulation in subjects undergoing a controlled ovarian stimulation, followed by oocyte pick-up and ARTs. Ovitrelle®, active ingredient human chorionic-gonadotropin alfa, is administered to trigger final follicular maturation and luteinization after stimulation of follicular growth.

OBJECTIVES

Primary objective:

* To compare the hormonal level of plasmatic estradiol on the releasing day (day of r-hCG administration) induced by Cetrotide® 0.25 mg/day started on Day 1 (Group A: Day 1) or on Day 7 (Group B: Day 7) of the menstrual cycle (Day 0 (S0) or Day 6 (S6) of stimulation) in PCO subjects undergoing IVF/ICSI procedures.

Secondary objectives:

* To compare the hormonal changes during the stimulation induced by Cetrotide® in A and B Groups
* To assess by ultrasound scans (US) the follicular development induced by Cetrotide® in A and B Groups
* To assess biological and clinical outcomes induced by Cetrotide® in A and B Groups
* To monitor safety of Cetrotide in A and B Groups

The trial will be conducted on an outpatient basis. Once each subject has met all eligibility criteria, they will be randomly assigned in one of the two treatment groups.

Eligibility criteria: Inclusion Criteria:

* Female subjects with PCO or Polycystic ovary syndrome (PCOS) according to the revised 2003 Rotterdam Consensus
* Female subjects suitable for IVF/ICSI, undergoing first or second attempt
* 18-35 years old, Body Mass Index (BMI) less than or equal to 32, non-smoking at least from Visit 0 (V0)
* Normal FSH value (less than 10 international unit per liter \[IU/L\]) on Day 3 of spontaneous cycle within 12 months prior to the trial
* Anti Mullerian Hormone (AMH) value (greater than 1.5 nanogram per milliliter \[ng/mL\]) of a spontaneous cycle within 12 months prior to the trial or at least at V0
* No history of active genito-urinary infection
* Normal thyroid function (or adequate substitution for at least 3 months)
* Negative cervical papanicolaou test within the last 12 months prior to study entry
* No gonadotropins, for at least one month prior to the trial
* No metformin therapy for at least one month prior to Visit 1 (V1)
* Subject who is able to participate in the trial and has provided written, informed consent.

Exclusion Criteria:

* Ongoing pregnancy, any pregnancy within 3 months prior to study entry, or any contraindication to pregnancy or carrying pregnancy to term
* Drilling 3 months prior to V0
* Uterine malformation, diethylstilbestrol syndrome, synechia
* Female subjects with World Health Organization (WHO) Type I or III anovulation
* Female subjects with hyperprolactinemia
* Female subjects with more than 2 recurrent miscarriages (early or late, and for any reasons)
* Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus, for subject or partner
* Abnormal gynecological bleeding of undetermined origin
* History of major thromboembolic disease
* Endometriosis (Grade III or IV)
* Presence or history of malignant tumors and related treatment
* Known case of tumors of the hypothalamus or pituitary gland
* Clinically significant systemic disease or clinically significant abnormal hematology, chemistry, or urinalysis results at screening
* Known allergic reaction or hypersensitivity to Cetrotide® or Ovitrelle®
* Any active substance abuse or history of drug, medication or alcohol abuse in the past 5 years
* Participation in another clinical trial within 3 months prior to study entry.

Primary outcomes:
measure: Estradiol (E2) Levels on r-hCG Day
timeFrame: r-hCG day (end of stimulation cycle [approximately 15 days])
Secondary outcomes:
measure: Serum Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Levels
timeFrame: Day 1
measure: Serum Estradiol (E2) Levels
timeFrame: Day 1
measure: Serum Progesterone (P4) Levels
timeFrame: Day 1
measure: Anti Mullerian Hormone (AMH) Levels
timeFrame: Day 0
measure: Number of Follicles Greater Than or Equal (>=) to 17 mm (For Day 1 Protocol) or 19 mm (For Day 7 Protocol) on r-hCG Day
timeFrame: r-hCG day (end of stimulation cycle [approximately 15 days])
measure: Number and Quality of Oocytes Retrieved
timeFrame: Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
measure: Total Dose of Recombinant Human Follicle Stimulating Hormone (r-hFSH)
timeFrame: Day 1 up to r-hCG day (end of stimulation cycle [approximately 15 days])
measure: Percentage of Fertilized Oocytes Retrieved
timeFrame: Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
measure: Number of Embryos
timeFrame: Day 2-3 post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
measure: Number of Blastocysts
timeFrame: Day 5-6 post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
measure: Number of Transferred Embryos
timeFrame: Day 2-3 post Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
measure: Implantation Rate
timeFrame: 5 weeks post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
measure: Percentage of Participants With Clinical Pregnancy
timeFrame: 10 weeks post r-hCG day (end of stimulation cycle [approximately 15 days])
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to end of study (15 days post last administration of study drug)
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Research Site
Study officials:
affiliation: Merck Lipha Santé
name: Dr Etienne VARLAN
role: STUDY_DIRECTOR
References: