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

Primary Purpose

Polycystic Ovarian Syndrome

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Cetrorelix acetate
Cetrorelix acetate
Recombinant Human Choriogonadotropin (r-hCG)
Recombinant human follicle stimulating hormone (r-hFSH)
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycystic Ovarian Syndrome focused on measuring Cetrorelix acetate; follitropin alfa; human chorionic-gonadotropin alfa; follicular maturation; pregnancy; ovarian stimulation

Eligibility Criteria

18 Years - 35 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Day 1 protocol

Day 7 protocol

Arm Description

Outcomes

Primary Outcome Measures

Estradiol (E2) Levels on r-hCG Day

Secondary Outcome Measures

Serum Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Levels
Serum Estradiol (E2) Levels
Serum Progesterone (P4) Levels
Anti Mullerian Hormone (AMH) Levels
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
Number and Quality of Oocytes Retrieved
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)
Percentage of Fertilized Oocytes Retrieved
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
Embryo is defined as the product of the zygote, two or three days after fertilization of the oocytes.
Number of Blastocysts
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
Embryo transfer is the procedure in which one or more embryos are placed in the uterus.
Implantation Rate
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
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)
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.

Full Information

First Posted
August 10, 2010
Last Updated
January 20, 2014
Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Serono S.A.S, France
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1. Study Identification

Unique Protocol Identification Number
NCT01185704
Brief Title
Analysis of Two Therapeutic With Cetrotide® in Polycystic Ovarian (PCO) Women in Assisted Reproductive Technology (ART)
Acronym
ATTAC-PCO
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

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Serono S.A.S, France

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovarian Syndrome
Keywords
Cetrorelix acetate; follitropin alfa; human chorionic-gonadotropin alfa; follicular maturation; pregnancy; ovarian stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
136 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Day 1 protocol
Arm Type
Experimental
Arm Title
Day 7 protocol
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cetrorelix acetate
Other Intervention Name(s)
Cetrotide®
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Cetrorelix acetate
Other Intervention Name(s)
Cetrotide®
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Recombinant Human Choriogonadotropin (r-hCG)
Other Intervention Name(s)
Ovitrelle®
Intervention Description
The r-hCG will be administered subcutaneously as a single dose of 250 microgram (mcg) on r-hCG day
Intervention Type
Drug
Intervention Name(s)
Recombinant human follicle stimulating hormone (r-hFSH)
Intervention Description
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
Primary Outcome Measure Information:
Title
Estradiol (E2) Levels on r-hCG Day
Time Frame
r-hCG day (end of stimulation cycle [approximately 15 days])
Secondary Outcome Measure Information:
Title
Serum Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Levels
Time Frame
Day 1
Title
Serum Estradiol (E2) Levels
Time Frame
Day 1
Title
Serum Progesterone (P4) Levels
Time Frame
Day 1
Title
Anti Mullerian Hormone (AMH) Levels
Time Frame
Day 0
Title
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])
Title
Number and Quality of Oocytes Retrieved
Description
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.
Time Frame
Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
Title
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])
Title
Percentage of Fertilized Oocytes Retrieved
Description
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.
Time Frame
Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
Title
Number of Embryos
Description
Embryo is defined as the product of the zygote, two or three days after fertilization of the oocytes.
Time Frame
Day 2-3 post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
Title
Number of Blastocysts
Description
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.
Time Frame
Day 5-6 post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
Title
Number of Transferred Embryos
Description
Embryo transfer is the procedure in which one or more embryos are placed in the uterus.
Time Frame
Day 2-3 post Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
Title
Implantation Rate
Description
Implantation rate per reporting group was measured as the number of gestational sacs observed, divided by the number of embryos transferred multiplied by 100.
Time Frame
5 weeks post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
Title
Percentage of Participants With Clinical Pregnancy
Description
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.
Time Frame
10 weeks post r-hCG day (end of stimulation cycle [approximately 15 days])
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
Day 1 up to end of study (15 days post last administration of study drug)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr Etienne VARLAN
Organizational Affiliation
Merck Lipha Santé
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Toulouse
Country
France

12. IPD Sharing Statement

Learn more about this trial

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

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