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

Infertility Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00805935
• Other study ID #: 2008-05
• Status: Completed
• Phase: Phase 4
• First received: December 9, 2008
• Last updated: January 26, 2012
• Start date: January 2009
• Est. completion date: September 2010

Study information

• Verified date: January 2012
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: September 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

Inclusion Criteria:

1. Pre-menopausal females between the ages of 18 and 42 years

2. 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

3. Body mass index (BMI) of 18-39

4. Early follicular phase (Day 3) follicle stimulating hormone (FSH) < 15 IU/L and estradiol (E2) within normal limits

5. 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.)

6. Transvaginal ultrasound at screening consistent with findings adequate for assisted reproductive technology (ART) with respect to uterus and adnexa

7. Signed informed consent

Exclusion Criteria:

1. Gestational or surrogate carrier, donor oocyte

2. 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)

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. 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

5. History of recurrent pregnancy loss, defined as more than two clinical losses

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])

11. Prior hypersensitivity to any of the protocol drugs

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility
• Polycystic Ovarian Syndrome
• Polycystic Ovary Syndrome
• Syndrome

Intervention

Drug:
• Menotropin
225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days.
• 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.
• Follitropin beta
225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Center for Assisted Reproduction	Bedford	Texas
United States	Fertility Center of Illinois	Chicago	Illinois
United States	Women's Medical Research Group LLC, Florida	Clearwater	Florida
United States	Conceptions Reproductive Associates of Colorado	Littleton	Colorado
United States	Weill Cornell Medical College	New York	New York
United States	Women & Infants' Hospital of RI	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Number of Follicles Observed at Day 15	The mean number of follicles observed in both ovaries at the last transvaginal ultrasound in the stimulation phase.	approximately day 15	No
Secondary	Number of Oocytes Retrieved at Day 18	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.	approximately day 18	No
Secondary	Percentage of Oocytes Fertilized of the Total Number of Oocytes Retrieved	The fertilization rate for each participant was the percentage of the number of oocytes inseminated of the total number of oocytes retrieved.	approximately day 19	No
Secondary	Number of Embryos Transferred at Three Stages of Development Before Implantation	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.	approximately day 24	No
Secondary	Number of Embryos Frozen	The number of embryos that were not transferred but instead were frozen for future use.	approximately day 24	No
Secondary	Percentage of Participants With Biochemical Pregnancy at Approximately Day 38	Biochemical pregnancy is a positive ß-hCG pregnancy test 12-14 days post embryo transfer.	approximately day 38 (Day 14 post embryo transfer)	No
Secondary	Percentage of Participants With Clinical Pregnancy at Week 7	Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.	approximately Day 52	No
Secondary	Percentage of Participants With Ongoing Pregnancy at Week 9	Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.	approximately Day 65	No
Secondary	Estradiol Levels at Day 6	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.	Day 6	No
Secondary	Human Chorionic Gonadotropin (hCG) Levels at Day 6	Blood tests were sent to a central laboratory to obtain hCG levels.	Day 6	No
Secondary	Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration	Blood tests were sent to a central laboratory to obtain progesterone levels.	approximately day 16	No
Secondary	Number of Live Births Resulting From the In Vitro Fertilization Process	Number of live births resulting from the IVF process	Approximately 10 months	No
Secondary	Participants With Treatment Emergent Adverse Events	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.	Week 1 to week12	No