MedPath

MENOPUR® Versus FOLLISTIM®

Phase 4
Completed
Conditions
Infertility
Interventions
Registration Number
NCT00802360
Lead Sponsor
Ferring Pharmaceuticals
Brief Summary

To compare the efficacy and safety of highly purified menotropin (Menopur®) with that of follitropin beta (FOLLISTIM®) in patients who are undergoing gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles

Detailed Description

This multicenter, randomized, open-label exploratory study will be performed in approximately 200 healthy females undergoing in vitro fertilization (IVF). Each study center will follow its study center standard practice for in vitro fertilization (IVF) within the study parameters as noted in this protocol. The study centers will use marketed products purchased from Schraft's Pharmacy for all phases of the study (down-regulation, stimulation, ovulation induction, and luteal support). Subjects will be randomly assigned prior to the start of stimulation to highly purified menotropin (Menopur®) or follitropin beta (Follistim Pen®) for stimulation and progesterone vaginal insert (Endometrin®) or progesterone in oil for luteal support. Subjects will return to the study center for regular scheduled clinic visits as required per in vitro fertilization (IVF) protocol at the site and at specified time periods during the cycle for estradiol (E2), progesterone (P4) and human chorionic gonadotropin (hCG) tests, and first serum pregnancy test. All subjects will be required to complete a final study visit at completion of luteal support or negative serum pregnancy test following embryo transfer.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
173
Inclusion Criteria
  1. Pre-menopausal females between the ages of 18 and 42 years
  2. Body mass index (BMI) of 18-34
  3. Early follicular phase (day 2-4) Follicle stimulating hormone (FSH) <15 IU/L and Estradiol (E2) within normal limits
  4. Documented history of infertility (e.g., unable to conceive for at least one year, or for 6 months for women >38 years of age, or bilateral tubal occlusion or absence, or male factor but excluding severe male factor requiring invasive or surgical sperm retrieval. Donor sperm may be used.)
  5. Transvaginal ultrasound at screening consistent with findings adequate for assisted reproductive technology (ART) with respect to uterus and adnexa
  6. Signed informed consent
Exclusion Criteria
  1. Gestational or surrogate carrier, donor oocyte
  2. Presence of any clinically relevant systemic disease (e.g., insulin-dependent diabetes mellitus, uterine cancer)
  3. Surgical or medical condition which, in the judgment of the Investigator or Sponsor, may interfere with absorption, distribution, metabolism, or excretion of the drugs to be used
  4. Previous In vitro fertilization (IVF) or Assisted reproductive technology (ART) failure due to a poor response to gonadotropins. Poor response is defined as development of 2 mature follicles or history of >2 previous failed in vitro fertilization (IVF) cycles.
  5. History of recurrent pregnancy loss (>2).
  6. Presence of abnormal uterine bleeding of undetermined origin
  7. Current or recent substance abuse, including alcohol or smoking >10 cigarettes per day
  8. Refusal or inability to comply with the requirements of the Protocol for any reason, including scheduled clinic visits and laboratory tests
  9. Participation in any experimental drug study within 30 days prior to Screening
  10. Severe male factor requiring invasive or surgical sperm retrieval (e.g., microsurgical epididymal sperm aspiration [MESA], testicular sperm extraction [TESE])

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Menopur/EndometrinProgestrone vaginal insertHighly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progestrone vaginal insert (Endometrin®) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Menopur/Progesterone in OilProgesterone in oilHighly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in Oil injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Follistim/EndometrinProgestrone vaginal insertFollitropin beta (Follistim®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progestrone vaginal insert (Endometrin®) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Follistim/EndometrinGanirelixFollitropin beta (Follistim®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progestrone vaginal insert (Endometrin®) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Follistim/Progesterone in OilProgesterone in oilFollitropin beta (Follistim®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in Oil injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Menopur/EndometrinMenotropinHighly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progestrone vaginal insert (Endometrin®) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Menopur/EndometrinGanirelixHighly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progestrone vaginal insert (Endometrin®) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Menopur/Progesterone in OilMenotropinHighly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in Oil injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Menopur/Progesterone in OilGanirelixHighly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in Oil injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Follistim/Endometrinfollitropin betaFollitropin beta (Follistim®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progestrone vaginal insert (Endometrin®) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Follistim/Progesterone in Oilfollitropin betaFollitropin beta (Follistim®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in Oil injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Follistim/Progesterone in OilGanirelixFollitropin beta (Follistim®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in Oil injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Ongoing Pregnancy at Week 8Week 8 (Week 6 of gestation)

The ongoing pregnancy was defined as a positive fetal heart movement (motion) at approximately six weeks of gestation and confirmed in a follow-up pregnancy ultrasound.

Secondary Outcome Measures
NameTimeMethod
Number of Follicles Observed at Day 15Day 15

The mean number of follicles observed in both ovaries at the last transvaginal ultrasound in the stimulation phase.

Number of Oocytes Retrieved at Day 18Approximately Day 18

The mean number of oocytes retrieved within 34-36 hours of human chorionic gonadotropin (hCG) administration.

Proportion of Oocytes Fertilized of the Total Number of Oocytes RetrievedApproximately Day 19

The proportion of the number of oocytes inseminated (fertilized) of the total number of oocytes retrieved.

Number of Embryos Transferred at Three Stages of DevelopmentApproximately Day 24

The number of embryos, morula and blastocytes transferred to the study participant on either day 3 or day 5 following fertilization.

Number of Embryos Frozen at Day 24Approximately Day 24

The number of embryos that were not transferred but instead were frozen for future use.

Participants With Cycle Cancellation Following One In Vitro Fertilization (IVF) Treatment CycleDay 1 to Day 24

A count of participants whose discontinuation was clearly documented on the study completion/termination form as 1) due to cycle cancelled or 2) cycle cancellation for risk of ovarian hyperstimulation syndrome (OHSS).

Participants With Biochemical Pregnancy at Day 38approximately day 38 (Day 14 post embryo transfer)

Biochemical pregnancy is a positive β-hCG pregnancy test 12-14 days post embryo transfer.

Participants With Clinical Pregnancy at Week 7approximately week 7

Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.

Participants With Adverse Events (AEs), Including Ovarian Hyperstimulation Syndrome (OHSS)Day 1 - week 12

Number of participants with adverse events (AEs) that started after first treatment. Severity used a three point scale:

mild=awareness of signs/symptoms, but no disruption of usual activity moderate=event sufficient to affect usual activity (disturbing) severe=event causes inability to work or perform usual activities (unacceptable)

Relatedness to study treatment used a four point scale: unrelated, unlikely, possible, probable.

Seriousness refers to death, hospitalization, a life-threatening experience, persistent or significant disability/incapacity, or congenital anomaly.

Number of Live BirthsApproximately 10 months

Trial Locations

Locations (7)

A Woman's Center for Reproductive Medicine

🇺🇸

Baton Rouge, Louisiana, United States

Huntington Reproductive Center

🇺🇸

Pasadena, California, United States

Women's Medical Research Group, LLC

🇺🇸

Clearwater, Florida, United States

San Diego Fertility Center

🇺🇸

San Diego, California, United States

The Advanced IVF Institute; Charles E. Miller, MD & Associates

🇺🇸

Naperville, Illinois, United States

Center for Assisted Reproduction

🇺🇸

Bedford, Texas, United States

Conceptions Reproductive Associates of Colorado

🇺🇸

Littleton, Colorado, United States

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