Menopur® Versus Follistim® in Polycystic Ovarian Syndrome (PCOS)

NCT00805935 | Completed Phase 4 Results

• 1 other identifier: 2008-05
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 6

Brief Summary

This multicenter, randomized, open-label exploratory study will be performed in approximately 200 polycystic ovary syndrome (PCOS) but otherwise healthy females undergoing in vitro fertilization (IVF). Each study center will follow its 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 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 times during the cycle (Stimulation Day 6, Day of human chorionic gonadotropin (hCG), and first serum pregnancy test) for estradiol (E2), progesterone (P4) and human chorionic gonadotropin (hCG) labs. All subjects will be required to complete a final study visit at completion of luteal support or negative serum pregnancy test following embryo transfer.

Conditions

Polycystic Ovarian Syndrome; Infertility

Keywords

pre-menopausal women; PCOS; polycystic ovarian syndrome; infertility; IVF; in vitro fertilization

Outcome Measures

Primary Outcomes (1)

• Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3

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

  weeks 1-3

Secondary Outcomes (13)

• Number of Follicles Observed at Day 15

  approximately day 15

• Number of Oocytes Retrieved at Day 18

  approximately day 18

• Percentage of Oocytes Fertilized of the Total Number of Oocytes Retrieved

  approximately day 19

• Number of Embryos Transferred at Three Stages of Development Before Implantation

  approximately day 24

• Number of Embryos Frozen

  approximately day 24

Study Arms (4)

Menotropin/Progesterone vaginal insert

EXPERIMENTAL

Highly 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 vaginal insert (Endometrin®) 100 mg starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.

Drug: Menotropin; Drug: Progesterone vaginal insert; Drug: leuprolide acetate

Menotropin/Progesterone in oil

EXPERIMENTAL

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 50 mg 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.

Drug: Menotropin; Drug: Progesterone in oil; Drug: leuprolide acetate

Follitropin beta/Progesterone vaginal insert

ACTIVE COMPARATOR

Follitropin beta (Follistim Pen®) 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 vaginal insert (Endometrin®) 50 mg 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.

Drug: Progesterone vaginal insert; Drug: Follitropin beta; Drug: leuprolide acetate

Follitropin beta/Progesterone in oil

ACTIVE COMPARATOR

Follitropin beta (Follistim Pen®) 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 50 mg 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.

Drug: Follitropin beta; Drug: Progesterone in oil; Drug: leuprolide acetate

Interventions

Menotropin DRUG

225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days.

Also known as: Menopur®

Menotropin/Progesterone in oil; Menotropin/Progesterone vaginal insert

Progesterone vaginal insert DRUG

100 mg inserted vaginally 2 or 3 times daily (BID or TID) (start on the day after oocyte retrieval) until 10 weeks gestation or confirmation of negative pregnancy test.

Also known as: Endometrin®

Follitropin beta/Progesterone vaginal insert; Menotropin/Progesterone vaginal insert

Follitropin beta DRUG

225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days.

Also known as: Follistim Pen®

Follitropin beta/Progesterone in oil; Follitropin beta/Progesterone vaginal insert

Progesterone in oil DRUG

50 mg by intramuscular injection once per day, starting on the day after oocyte retrieval until 10 weeks gestation or confirmation of negative pregnancy test.

Follitropin beta/Progesterone in oil; Menotropin/Progesterone in oil

leuprolide acetate DRUG

Daily administration of 0.5mg of leuprolide acetate (depot formulations were not permitted) began on Day 21 following onset of menses, and then decreased to 0.25 mg when gonadotropin therapy was initiated.

Also known as: Lupron

Follitropin beta/Progesterone in oil; Follitropin beta/Progesterone vaginal insert; Menotropin/Progesterone in oil; Menotropin/Progesterone vaginal insert

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Pre-menopausal females between the ages of 18 and 42 years
• Diagnosed with polycystic ovary syndrome (PCOS), using criteria adopted as the 2003 Rotterdam PCOS Consensus (2 out of 3, excluding other etiologies \[congenital adrenal hyperplasia, androgen-secreting tumors, Cushing's syndrome\])
• Oligo- or anovulation
• Clinical and/or biochemical signs of hyperandrogenism
• Polycystic ovaries
• Body mass index (BMI) of 18-39
• Early follicular phase (Day 3) follicle stimulating hormone (FSH) \< 15 IU/L and estradiol (E2) within normal limits
• 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.)
• Transvaginal ultrasound at screening consistent with findings adequate for assisted reproductive technology (ART) with respect to uterus and adnexa
• Signed informed consent

You may not qualify if:

• Gestational or surrogate carrier, donor oocyte
• Presence of any clinically relevant systemic disease (e.g., uncontrolled thyroid or adrenal dysfunction, an organic intracranial lesion such as a pituitary tumor, insulin-dependent diabetes mellitus, uterine cancer)
• 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
• Two or more previous failed in vitro fertilization (IVF) cycles or in vitro fertilization (IVF)/assisted reproductive technology (ART) failure due to a poor response to gonadotropins, defined as development of 2 mature follicles
• History of recurrent pregnancy loss, defined as more than two clinical losses
• Presence of abnormal uterine bleeding of undetermined origin
• Current or recent substance abuse, including alcohol or smoking \> 10 cigarettes per day
• Refusal or inability to comply with the requirements of the Protocol for any reason, including scheduled clinic visits and laboratory tests
• Participation in any experimental drug study within 30 days prior to Screening
• Severe male factor requiring invasive or surgical sperm retrieval (e.g., microsurgical epididymal sperm aspiration \[MESA\], testicular sperm extraction \[TESE\])
• Prior hypersensitivity to any of the protocol drugs

Sponsors & Collaborators

• Ferring Pharmaceuticals: lead

Study Sites (6)

Conceptions Reproductive Associates of Colorado

Littleton, Colorado, 80129, United States

Location

Women's Medical Research Group LLC, Florida

Clearwater, Florida, 33759, United States

Location

Fertility Center of Illinois

Chicago, Illinois, 60610, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Women & Infants' Hospital of RI

Providence, Rhode Island, 02905, United States

Location

Center for Assisted Reproduction

Bedford, Texas, 76022, United States

Location

Related Publications (1)

• Beltsos AN, Sanchez MD, Doody KJ, Bush MR, Domar AD, Collins MG. Patients' administration preferences: progesterone vaginal insert (Endometrin(R)) compared to intramuscular progesterone for Luteal phase support. Reprod Health. 2014 Nov 11;11:78. doi: 10.1186/1742-4755-11-78.

  PMID: 25385669 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Infertility

Interventions

Menotropins; Progesterone; follitropin beta; Oils; Leuprolide

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins; Biological Products; Complex Mixtures; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Progesterone Congeners; Gonadal Steroid Hormones; Lipids; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Neuropeptides; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Clinical Development Support
• Organization: Ferring Pharmaceuticals

DK0-Disclosure@ferring.com

Study Officials

• Clinical Development Support

  Ferring Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2008
• First Posted: December 10, 2008
• Study Start: January 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: September 1, 2010
• Last Updated: January 27, 2012
• Results First Posted: January 25, 2012

Record last verified: 2012-01

Locations

US (6)