Analysis of Two Therapeutic With Cetrotide® in Polycystic Ovarian (PCO) Women in Assisted Reproductive Technology (ART) (ATTAC-PCO)

This study has been completed.
Sponsor:
Collaborator:
Merck Serono S.A.S, France
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01185704
First received: August 10, 2010
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

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).


Condition Intervention Phase
Polycystic Ovarian Syndrome
Drug: Cetrorelix acetate
Drug: Recombinant Human Choriogonadotropin (r-hCG)
Drug: Recombinant human follicle stimulating hormone (r-hFSH)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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).

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Estradiol (E2) Levels on r-hCG Day [ Time Frame: r-hCG day (end of stimulation cycle [approximately 15 days]) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serum Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Levels [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Serum Estradiol (E2) Levels [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Serum Progesterone (P4) Levels [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Anti Mullerian Hormone (AMH) Levels [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: r-hCG day (end of stimulation cycle [approximately 15 days]) ] [ Designated as safety issue: No ]
  • Number and Quality of Oocytes Retrieved [ Time Frame: Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}]) ] [ Designated as safety issue: No ]
    Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocytes from the ovary of the female participant, enabling fertilization outside the body. Oocytes were classified into 4 different categories based on their quality: mature, fractured, immature and inseminated oocytes.

  • Total Dose of Recombinant Human Follicle Stimulating Hormone (r-hFSH) [ Time Frame: Day 1 up to r-hCG day (end of stimulation cycle [approximately 15 days]) ] [ Designated as safety issue: No ]
  • Percentage of Fertilized Oocytes Retrieved [ Time Frame: Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}]) ] [ Designated as safety issue: No ]
    Oocytes were fertilized using Intra-cytoplasmic Sperm Injection (ICSI) technique which is an IVF procedure in which a single sperm is injected directly into an egg under a microscope.

  • Number of Embryos [ Time Frame: Day 2-3 post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}]) ] [ Designated as safety issue: No ]
    Embryo is defined as the product of the zygote, two or three days after fertilization of the oocytes.

  • Number of Blastocysts [ Time Frame: Day 5-6 post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}]) ] [ Designated as safety issue: No ]
    Blastocyst is an embryo, five or six days after fertilization, with an inner cell mass, outer layer of trophectoderm and a fluid-filled blastocoele cavity.

  • Number of Transferred Embryos [ Time Frame: Day 2-3 post Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}]) ] [ Designated as safety issue: No ]
    Embryo transfer is the procedure in which one or more embryos are placed in the uterus.

  • Implantation Rate [ Time Frame: 5 weeks post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}]) ] [ Designated as safety issue: No ]
    Implantation rate per reporting group was measured as the number of gestational sacs observed, divided by the number of embryos transferred multiplied by 100.

  • Percentage of Participants With Clinical Pregnancy [ Time Frame: 10 weeks post r-hCG day (end of stimulation cycle [approximately 15 days]) ] [ Designated as safety issue: No ]
    Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy.

  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to end of study (15 days post last administration of study drug) ] [ Designated as safety issue: Yes ]
    An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. To avoid the participant/event combination double-count AEs and SAEs are reported separately.


Enrollment: 136
Study Start Date: November 2008
Study Completion Date: February 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Day 1 protocol Drug: Cetrorelix acetate
Cetrotide® 0.25 mg will be administered subcutaneously once daily from Day 1 (Day 0 of stimulation period [S0]) until r-hCG day (at least 2 follicles >=17 mm)
Other Name: Cetrotide®
Drug: Recombinant Human Choriogonadotropin (r-hCG)
The r-hCG will be administered subcutaneously as a single dose of 250 microgram (mcg) on r-hCG day
Other Name: Ovitrelle®
Drug: Recombinant human follicle stimulating hormone (r-hFSH)
Recombinant human follicle stimulating hormone (r-hFSH) will be administered subcutaneously at a dose between 75 and 187.5 international unit (IU) once daily from Day 2 (Day 1 of stimulation period [S1]) until r-hCG day
Experimental: Day 7 protocol Drug: Cetrorelix acetate
Cetrotide® 0.25 mg will be administered subcutaneously once daily from Day 7 (Day 6 of stimulation period [S6]) until r-hCG day (at least 2 follicles >=19 mm)
Other Name: Cetrotide®
Drug: Recombinant Human Choriogonadotropin (r-hCG)
The r-hCG will be administered subcutaneously as a single dose of 250 microgram (mcg) on r-hCG day
Other Name: Ovitrelle®
Drug: Recombinant human follicle stimulating hormone (r-hFSH)
Recombinant human follicle stimulating hormone (r-hFSH) will be administered subcutaneously at a dose between 75 and 187.5 international unit (IU) once daily from Day 2 (Day 1 of stimulation period [S1]) until r-hCG day

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

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01185704

Locations
France
Research Site
Toulouse, France
Sponsors and Collaborators
Merck KGaA
Merck Serono S.A.S, France
Investigators
Study Director: Dr Etienne VARLAN Merck Lipha Santé
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01185704     History of Changes
Other Study ID Numbers: EMR200088-501, 2007-007932-25, INI 28091
Study First Received: August 10, 2010
Results First Received: March 25, 2013
Last Updated: January 20, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Merck KGaA:
Cetrorelix acetate; follitropin alfa; human chorionic-gonadotropin alfa; follicular maturation; pregnancy; ovarian stimulation

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Chorionic Gonadotropin
Hormones
Follicle Stimulating Hormone
Cetrorelix
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on April 17, 2014