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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00298025
First received: February 27, 2006
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Infertile Women Undergoing Assisted Reproductive Technology (ART)
Drug: Cetrotide®
Drug: Antagon ™
Drug: Recombinant human follicle stimulating hormone (r-hFSH)
Drug: Human Menopausal Gonadotropin (hMG)
Drug: Recombinant Human Choriogonadotropin (r-hCG)
Phase 4

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 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

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Percentage of subjects without premature luteinizing hormone (LH) surge [ Time Frame: r-hCG administration day (end of stimulation cycle {approximately 4 days}) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of study treatment [ Time Frame: Stimulation Day 1 (S1) up to r-hCG administration day (end of stimulation cycle {approximately 4 days}) ] [ Designated as safety issue: No ]
  • 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}) ] [ Designated as safety issue: No ]
  • Duration of gonadotropin therapy [ Time Frame: Stimulation Day 1 (S1) up to r-hCG administration day (end of stimulation cycle {approximately 4 days}) ] [ Designated as safety issue: No ]
  • 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}) ] [ Designated as safety issue: No ]
  • 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}]) ] [ Designated as safety issue: No ]
  • Number of mature oocytes retrieved [ Time Frame: OPU day (34-38 hours post r-hCG administration day [end of stimulation cycle {approximately 4 days}]) ] [ Designated as safety issue: No ]
  • 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}]) ] [ Designated as safety issue: No ]
  • 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}]) ] [ Designated as safety issue: No ]
  • Implantation rate [ Time Frame: Day 35-42 post r-hCG administration day (end of stimulation cycle {approximately 4 days}) ] [ Designated as safety issue: No ]
  • 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}]) ] [ Designated as safety issue: No ]
  • 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}) ] [ Designated as safety issue: No ]
  • 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}) ] [ Designated as safety issue: No ]

Enrollment: 185
Study Start Date: September 2003
Study Completion Date: May 2004
Primary Completion Date: May 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetrotide® Drug: Cetrotide®
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.
Other Name: Cetrorelix acetate
Drug: Recombinant human follicle stimulating hormone (r-hFSH)
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.
Other Name: Gonal-f®
Drug: Human Menopausal Gonadotropin (hMG)
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).
Other Name: Pergonal®
Drug: Recombinant Human Choriogonadotropin (r-hCG)
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.
Other Names:
  • Ovidrel®
  • Choriogonadotropin alfa
Active Comparator: Antagon ™ Drug: Antagon ™
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.
Other Name: Ganirelix acetate
Drug: Recombinant human follicle stimulating hormone (r-hFSH)
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.
Other Name: Gonal-f®
Drug: Human Menopausal Gonadotropin (hMG)
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).
Other Name: Pergonal®
Drug: Recombinant Human Choriogonadotropin (r-hCG)
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.
Other Names:
  • Ovidrel®
  • Choriogonadotropin alfa

  Eligibility

Ages Eligible for Study:   18 Years to 39 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00298025

Sponsors and Collaborators
EMD Serono
Investigators
Study Director: Eduardo Kelly, MD, MBA EMD Serono
  More Information

Additional Information:
Publications:
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00298025     History of Changes
Other Study ID Numbers: 24688
Study First Received: February 27, 2006
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by EMD Serono:
Infertility
Cetrotide
Antagon
Recombinant human follicle stimulating hormone (r-hFSH)
Human Menopausal Gonadotropin (hMG)
Recombinant Human Choriogonadotropin (r-hCG)

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Chorionic Gonadotropin
Menotropins
Cetrorelix
Hormones
Follicle Stimulating Hormone
Ganirelix
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Hormones, Hormone Substitutes, and Hormone Antagonists
Fertility Agents, Female
Fertility Agents
Hormone Antagonists

ClinicalTrials.gov processed this record on August 21, 2014