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A Study to Compare the Safety and Efficacy of Cetrotide® 3 Milligram (mg) Versus Antagon™ in Women Undergoing Ovarian Stimulation

Primary Purpose

Infertile Women Undergoing Assisted Reproductive Technology (ART)

Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Cetrotide®
Antagon ™
Recombinant human follicle stimulating hormone (r-hFSH)
Human Menopausal Gonadotropin (hMG)
Recombinant Human Choriogonadotropin (r-hCG)
Sponsored by
EMD Serono
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertile Women Undergoing Assisted Reproductive Technology (ART) focused on measuring Infertility, Cetrotide, Antagon, Recombinant human follicle stimulating hormone (r-hFSH), Human Menopausal Gonadotropin (hMG), Recombinant Human Choriogonadotropin (r-hCG)

Eligibility Criteria

18 Years - 39 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Infertile women wishing to conceive whose physician had recommended that she can undergo ART Aged 18-39 years (inclusive) Regular menstrual cycles every 25-35 days Body mass index (BMI) less than 35 kilogram per square meter (kg/m^2) Has a transvaginal pelvic ultrasound scan within 6 weeks prior to OCP administration, as well as an Hysterosalpingography (HSG) or hysterosonogram or hysteroscopy within three years prior to OCP administration showing no clinically significant pelvic and/or uterine abnormality, which, in the Investigator's opinion, could impair ovarian response, embryo implantation or pregnancy continuation Normal cervical cytology, documented by Pap Smear, within six months prior to OCP administration If the subject had prior stimulation cycles, at least a 60-day washout period is required after the last dose of gonadotropin or clomiphene citrate; a 60-day washout is required after the last dose of Lupron® or Lupron Depot® 1-month; a 180-day washout period is required after the last dose of treatment with Depo-Provera® and Lupron Depot® 6-month; a 60-day washout is required after the last dose of oral contraceptives prior to OCP administration in the study Screening laboratory results for follicle stimulating hormone (FSH) that are within the normal limit for the early follicular phase at the local laboratory Is willing and able to comply with the protocol for the duration of the study Has voluntarily provided written informed consent and a subject authorization under Health insurance portability and accountability act (HIPAA), prior to any study-related procedure that is not part of normal medical care, with the understanding that the subject could withdraw consent at any time without prejudice to her future medical care Exclusion Criteria: Clinically significant systemic disease Known to be infected with Human Immunodeficiency Virus (HIV) Known to be infected with Hepatitis C virus Known to test positive for Hepatitis B surface antigens Any medical condition, which, in the judgment of the Investigator and Sponsor, may interfere with the absorption, distribution, metabolism or excretion of the study drugs Known endometriosis Grade III-IV (American society of reproductive medicine [ASRM] classification) Uni- or bilateral hydrosalpinx Any contraindication to being pregnant and/or carrying pregnancy to term Any previous ART cycle indicating a poor response to gonadotropin stimulation (defined as retrieval of three oocytes or less) If, in a previous ART attempt, there are no motile sperm before or after the sperm processing with ejaculated, epididymal, testicular, fresh or frozen/thawed spermatozoa Three or more previous consecutive ART cycles without a clinical pregnancy An extrauterine pregnancy within the last three months before OCP treatment commences Abnormal, undiagnosed, gynecological bleeding Known allergy or hypersensitivity to human gonadotropin preparations or any other study-related medications Known current substance abuse Previous participation in this study or simultaneous participation in another clinical trial Current smoker

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Cetrotide®

    Antagon ™

    Arm Description

    Outcomes

    Primary Outcome Measures

    Percentage of subjects without premature luteinizing hormone (LH) surge

    Secondary Outcome Measures

    Duration of study treatment
    Total dose of recombinant human follicle stimulating hormone/human menopausal gonadotropin (r-hFSH/hMG) administered
    Duration of gonadotropin therapy
    Number of follicles greater than or equal to (>=) 14 millimeter (mm) on day of recombinant human chorionic gonadotropin (r-hCG) administration
    Number of oocytes retrieved
    Number of mature oocytes retrieved
    Number of fertilized oocytes
    Number and Quality of Embryos
    Implantation rate
    Total number of transferred and cryopreserved embryos
    Percentage of subjects with clinical and biochemical pregnancies
    Quality of Life assessed by Short Form- 36 (SF-36) Questionnaire

    Full Information

    First Posted
    February 27, 2006
    Last Updated
    March 24, 2014
    Sponsor
    EMD Serono
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00298025
    Brief Title
    A Study to Compare the Safety and Efficacy of Cetrotide® 3 Milligram (mg) Versus Antagon™ in Women Undergoing Ovarian Stimulation
    Official Title
    A Phase IV, Multicenter, Open-label, Randomized Study to Compare the Safety and Efficacy of Cetrotide® 3 mg Versus Antagon™ in the Inhibition of a Premature LH Surge in a r-hFSH/hMG Stimulation Cycle With OCP Programming in Women Undergoing Ovarian Stimulation Prior to ART
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2014
    Overall Recruitment Status
    Completed
    Study Start Date
    September 2003 (undefined)
    Primary Completion Date
    May 2004 (Actual)
    Study Completion Date
    May 2004 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    EMD Serono

    4. Oversight

    5. Study Description

    Brief Summary
    To demonstrate the comparative safety and efficacy of Cetrotide® 3 milligram (mg) and Antagon™ in the inhibition of a premature luteinizing hormone (LH) surge in women undergoing ovarian stimulation with recombinant human follicle stimulating hormone/human menopausal gonadotropin (r-hFSH/hMG) prior to assisted reproductive technology (ART) and utilizing oral contraceptives pill (OCP) for cycle programming.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Infertile Women Undergoing Assisted Reproductive Technology (ART)
    Keywords
    Infertility, Cetrotide, Antagon, Recombinant human follicle stimulating hormone (r-hFSH), Human Menopausal Gonadotropin (hMG), Recombinant Human Choriogonadotropin (r-hCG)

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    185 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Cetrotide®
    Arm Type
    Experimental
    Arm Title
    Antagon ™
    Arm Type
    Active Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    Cetrotide®
    Other Intervention Name(s)
    Cetrorelix acetate
    Intervention Description
    Cetrotide® will be administered subcutaneously as 3 mg injection when the lead follicle is >=14 mm till r-hCG day. If the subject did not achieve follicular maturation and did not receive r-hCG within 4 days, then the Cetrotide® will be administered at dose of 0.25 mg subcutaneously on successive days until r-hCG day.
    Intervention Type
    Drug
    Intervention Name(s)
    Antagon ™
    Other Intervention Name(s)
    Ganirelix acetate
    Intervention Description
    Antagon™ will be administered subcutaneously at a dose of 0.25 mg once daily when the lead follicle is >=14 mm until r-hCG day.
    Intervention Type
    Drug
    Intervention Name(s)
    Recombinant human follicle stimulating hormone (r-hFSH)
    Other Intervention Name(s)
    Gonal-f®
    Intervention Description
    Recombinant human follicle stimulating hormone (r-hFSH) will be administered at a starting dose of 225 international unit (IU) subcutaneously once daily from S1 up to Stimulation Day 5 (S5). Beginning on Stimulation Day 6 (S6), the r-hFSH dose will be individualized to the subject. The minimum and maximum daily doses are 75 IU and 450 IU, respectively until r-hCG day.
    Intervention Type
    Drug
    Intervention Name(s)
    Human Menopausal Gonadotropin (hMG)
    Other Intervention Name(s)
    Pergonal®
    Intervention Description
    Human menopausal gonadotropin (hMG) will be administered subcutaneously daily at a dose of 75 IU till r-hCG day. The total daily dose of r-hFSH and hMG combined is not to exceed 450 IU (375 IU r-hFSH and 75 IU hMG).
    Intervention Type
    Drug
    Intervention Name(s)
    Recombinant Human Choriogonadotropin (r-hCG)
    Other Intervention Name(s)
    Ovidrel®, Choriogonadotropin alfa
    Intervention Description
    The r-hCG will be administered as a single dose of 250 microgram (mcg) subcutaneously when there is at least one follicle of >=18 mm and two additional follicles of >=16 mm with an appropriate plasma estradiol levels for the number and size of the existing follicles. The r-hCG will be administered within 36 hours after the last dose of the r-hFSH/hMG.
    Primary Outcome Measure Information:
    Title
    Percentage of subjects without premature luteinizing hormone (LH) surge
    Time Frame
    r-hCG administration day (end of stimulation cycle {approximately 4 days})
    Secondary Outcome Measure Information:
    Title
    Duration of study treatment
    Time Frame
    Stimulation Day 1 (S1) up to r-hCG administration day (end of stimulation cycle {approximately 4 days})
    Title
    Total dose of recombinant human follicle stimulating hormone/human menopausal gonadotropin (r-hFSH/hMG) administered
    Time Frame
    Stimulation Day 1 (S1) up to r-hCG administration day (end of stimulation cycle {approximately 4 days})
    Title
    Duration of gonadotropin therapy
    Time Frame
    Stimulation Day 1 (S1) up to r-hCG administration day (end of stimulation cycle {approximately 4 days})
    Title
    Number of follicles greater than or equal to (>=) 14 millimeter (mm) on day of recombinant human chorionic gonadotropin (r-hCG) administration
    Time Frame
    r-hCG administration day (end of stimulation cycle {approximately 4 days})
    Title
    Number of oocytes retrieved
    Time Frame
    Ovum pick-up (OPU) day (34-38 hours post r-hCG administration day [end of stimulation cycle {approximately 4 days}])
    Title
    Number of mature oocytes retrieved
    Time Frame
    OPU day (34-38 hours post r-hCG administration day [end of stimulation cycle {approximately 4 days}])
    Title
    Number of fertilized oocytes
    Time Frame
    Day 1 post OPU day (34-38 hours post r-hCG administration day [end of stimulation cycle {approximately 4 days}])
    Title
    Number and Quality of Embryos
    Time Frame
    Day 2-3 post OPU (34-38 hours post r-hCG administration day [end of stimulation cycle {approximately 4 days}])
    Title
    Implantation rate
    Time Frame
    Day 35-42 post r-hCG administration day (end of stimulation cycle {approximately 4 days})
    Title
    Total number of transferred and cryopreserved embryos
    Time Frame
    Day 2-3 post OPU (34-38 hours post r-hCG administration day [end of stimulation cycle {approximately 4 days}])
    Title
    Percentage of subjects with clinical and biochemical pregnancies
    Time Frame
    Day 35-42 post r-hCG administration day (end of stimulation cycle {approximately 4 days})
    Title
    Quality of Life assessed by Short Form- 36 (SF-36) Questionnaire
    Time Frame
    Stimulation Day 1 (S1) and Day 15-18 post r-hCG administration (end of stimulation cycle {approximately 4 days})

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    39 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Infertile women wishing to conceive whose physician had recommended that she can undergo ART Aged 18-39 years (inclusive) Regular menstrual cycles every 25-35 days Body mass index (BMI) less than 35 kilogram per square meter (kg/m^2) Has a transvaginal pelvic ultrasound scan within 6 weeks prior to OCP administration, as well as an Hysterosalpingography (HSG) or hysterosonogram or hysteroscopy within three years prior to OCP administration showing no clinically significant pelvic and/or uterine abnormality, which, in the Investigator's opinion, could impair ovarian response, embryo implantation or pregnancy continuation Normal cervical cytology, documented by Pap Smear, within six months prior to OCP administration If the subject had prior stimulation cycles, at least a 60-day washout period is required after the last dose of gonadotropin or clomiphene citrate; a 60-day washout is required after the last dose of Lupron® or Lupron Depot® 1-month; a 180-day washout period is required after the last dose of treatment with Depo-Provera® and Lupron Depot® 6-month; a 60-day washout is required after the last dose of oral contraceptives prior to OCP administration in the study Screening laboratory results for follicle stimulating hormone (FSH) that are within the normal limit for the early follicular phase at the local laboratory Is willing and able to comply with the protocol for the duration of the study Has voluntarily provided written informed consent and a subject authorization under Health insurance portability and accountability act (HIPAA), prior to any study-related procedure that is not part of normal medical care, with the understanding that the subject could withdraw consent at any time without prejudice to her future medical care Exclusion Criteria: Clinically significant systemic disease Known to be infected with Human Immunodeficiency Virus (HIV) Known to be infected with Hepatitis C virus Known to test positive for Hepatitis B surface antigens Any medical condition, which, in the judgment of the Investigator and Sponsor, may interfere with the absorption, distribution, metabolism or excretion of the study drugs Known endometriosis Grade III-IV (American society of reproductive medicine [ASRM] classification) Uni- or bilateral hydrosalpinx Any contraindication to being pregnant and/or carrying pregnancy to term Any previous ART cycle indicating a poor response to gonadotropin stimulation (defined as retrieval of three oocytes or less) If, in a previous ART attempt, there are no motile sperm before or after the sperm processing with ejaculated, epididymal, testicular, fresh or frozen/thawed spermatozoa Three or more previous consecutive ART cycles without a clinical pregnancy An extrauterine pregnancy within the last three months before OCP treatment commences Abnormal, undiagnosed, gynecological bleeding Known allergy or hypersensitivity to human gonadotropin preparations or any other study-related medications Known current substance abuse Previous participation in this study or simultaneous participation in another clinical trial Current smoker
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Eduardo Kelly, MD, MBA
    Organizational Affiliation
    EMD Serono
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    16009165
    Citation
    Wilcox J, Potter D, Moore M, Ferrande L, Kelly E; CAP IV Investigator Group. Prospective, randomized trial comparing cetrorelix acetate and ganirelix acetate in a programmed, flexible protocol for premature luteinizing hormone surge prevention in assisted reproductive technologies. Fertil Steril. 2005 Jul;84(1):108-17. doi: 10.1016/j.fertnstert.2005.03.016.
    Results Reference
    background
    Links:
    URL
    http://dx.doi.org/10.1016/j.fertnstert.2005.03.016
    Description
    Study published in Fertility & Sterility 84(1):108-17;2005
    URL
    http://www.fertilitylifelines.com
    Description
    Full FDA approved prescribing information can be found here

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    A Study to Compare the Safety and Efficacy of Cetrotide® 3 Milligram (mg) Versus Antagon™ in Women Undergoing Ovarian Stimulation

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