Menopur® Versus Follistim® in Polycystic Ovarian Syndrome (PCOS) - Full Text View

Sponsor:	Ferring Pharmaceuticals
Information provided by (Responsible Party):	Ferring Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00805935

Purpose

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.

Condition	Intervention	Phase
Polycystic Ovarian Syndrome Infertility	Drug: Menotropin Drug: Progesterone vaginal insert Drug: Follitropin beta Drug: Progesterone in oil Drug: leuprolide acetate	Phase IV

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 Multi-Center, Randomized, Open-Label Evaluation of MENOPUR® Versus FOLLISTIM® in Polycystic Ovarian Syndrome (PCOS) Patients

Resource links provided by NLM:

MedlinePlus related topics: Infertility Polycystic Ovary Syndrome

Drug Information available for: Progesterone Leuprolide Menotropins Leuprolide acetate Follitropin beta Chorionic gonadotropin Follicle Stimulating Hormone

U.S. FDA Resources

Further study details as provided by Ferring Pharmaceuticals:

Primary Outcome Measures:

Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3 [ Time Frame: weeks 1-3 ] [ Designated as safety issue: No ]
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).

Secondary Outcome Measures:

Number of Follicles Observed at Day 15 [ Time Frame: approximately day 15 ] [ Designated as safety issue: No ]
The mean number of follicles observed in both ovaries at the last transvaginal ultrasound in the stimulation phase.
Number of Oocytes Retrieved at Day 18 [ Time Frame: approximately day 18 ] [ Designated as safety issue: No ]
The mean number of oocytes retrieved approximately 36 hours after hCG (Novarel®) administration and fertilized (by insemination or intra cytoplasmic sperm injection (ICSI)) according to site-specific procedures.
Percentage of Oocytes Fertilized of the Total Number of Oocytes Retrieved [ Time Frame: approximately day 19 ] [ Designated as safety issue: No ]
The fertilization rate for each participant was the percentage of the number of oocytes inseminated of the total number of oocytes retrieved.
Number of Embryos Transferred at Three Stages of Development Before Implantation [ Time Frame: approximately day 24 ] [ Designated as safety issue: No ]
The number of embryos, morulas and blastocysts transferred to the study participant on either day 3 or day 5 following fertilization. Embryos represent the earliest development stage and contain 2-8 cells.

Morulas, the next stage, continued cellular cleavage results in a 16-30 cell solid sphere. Morula further develop into blastocyst, which contains 70-100 cells in a hollow spherical shape.
Number of Embryos Frozen [ Time Frame: approximately day 24 ] [ Designated as safety issue: No ]
The number of embryos that were not transferred but instead were frozen for future use.
Percentage of Participants With Biochemical Pregnancy at Approximately Day 38 [ Time Frame: approximately day 38 (Day 14 post embryo transfer) ] [ Designated as safety issue: No ]
Biochemical pregnancy is a positive β-hCG pregnancy test 12-14 days post embryo transfer.
Percentage of Participants With Clinical Pregnancy at Week 7 [ Time Frame: approximately Day 52 ] [ Designated as safety issue: No ]
Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.
Percentage of Participants With Ongoing Pregnancy at Week 9 [ Time Frame: approximately Day 65 ] [ Designated as safety issue: No ]
Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.
Estradiol Levels at Day 6 [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
Estradiol monitoring during fertility therapy assesses follicular growth and is useful in monitoring the treatment. Blood tests sent to a central laboratory to obtain estradiol levels.
Human Chorionic Gonadotropin (hCG) Levels at Day 6 [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
Blood tests were sent to a central laboratory to obtain hCG levels.
Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration [ Time Frame: approximately day 16 ] [ Designated as safety issue: No ]
Blood tests were sent to a central laboratory to obtain progesterone levels.
Number of Live Births Resulting From the In Vitro Fertilization Process [ Time Frame: Approximately 10 months ] [ Designated as safety issue: No ]
Number of live births resulting from the IVF process
Participants With Treatment Emergent Adverse Events [ Time Frame: Week 1 to week12 ] [ Designated as safety issue: No ]
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.

Enrollment:	110
Study Start Date:	January 2009
Study Completion Date:	September 2010
Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Menotropin/Progesterone vaginal insert 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 225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days. Other Name: Menopur® Drug: Progesterone vaginal insert 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. Other Name: Endometrin® Drug: leuprolide acetate 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. Other Name: Lupron
Experimental: Menotropin/Progesterone in oil 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 225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days. Other Name: Menopur® Drug: Progesterone in oil 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. Drug: leuprolide acetate 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. Other Name: Lupron
Active Comparator: Follitropin beta/Progesterone vaginal insert 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 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. Other Name: Endometrin® Drug: Follitropin beta 225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days. Other Name: Follistim Pen® Drug: leuprolide acetate 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. Other Name: Lupron
Active Comparator: Follitropin beta/Progesterone in oil 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 225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days. Other Name: Follistim Pen® Drug: Progesterone in oil 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. Drug: leuprolide acetate 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. Other Name: Lupron

Eligibility

Ages Eligible for Study:	18 Years to 42 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00805935

Locations

United States, Colorado
Conceptions Reproductive Associates of Colorado
Littleton, Colorado, United States, 80129
United States, Florida
Women's Medical Research Group LLC, Florida
Clearwater, Florida, United States, 33759
United States, Illinois
Fertility Center of Illinois
Chicago, Illinois, United States, 60610
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10021
United States, Rhode Island
Women & Infants' Hospital of RI
Providence, Rhode Island, United States, 02905
United States, Texas
Center for Assisted Reproduction
Bedford, Texas, United States, 76022

Sponsors and Collaborators

Ferring Pharmaceuticals

Investigators

Study Director:

Clinical Development Support

Ferring Pharmaceuticals

More Information

No publications provided

Responsible Party:	Ferring Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00805935 History of Changes
Other Study ID Numbers:	2008-05
Study First Received:	December 9, 2008
Results First Received:	November 28, 2011
Last Updated:	January 26, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Ferring Pharmaceuticals:

pre-menopausal women
PCOS
polycystic ovarian syndrome

infertility
IVF
in vitro fertilization

Additional relevant MeSH terms:

Infertility
Polycystic Ovary Syndrome
Genital Diseases, Male
Genital Diseases, Female
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
Chorionic Gonadotropin
Menotropins
Leuprolide

Progesterone
Follicle Stimulating Hormone
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Fertility Agents, Female
Fertility Agents
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 09, 2012