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

Primary Purpose

Polycystic Ovarian Syndrome, Infertility

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Menotropin

Progesterone vaginal insert

Follitropin beta

Progesterone in oil

leuprolide acetate

About this trial

This is an interventional treatment trial for Polycystic Ovarian Syndrome focused on measuring pre-menopausal women, PCOS, polycystic ovarian syndrome, infertility, IVF, in vitro fertilization

Eligibility Criteria

18 Years - 42 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Conceptions Reproductive Associates of Colorado
Women's Medical Research Group LLC, Florida
Fertility Center of Illinois
Weill Cornell Medical College
Women & Infants' Hospital of RI
Center for Assisted Reproduction

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

Menotropin/Progesterone vaginal insert

Menotropin/Progesterone in oil

Follitropin beta/Progesterone vaginal insert

Follitropin beta/Progesterone in oil

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

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.

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.

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.

Number of Embryos Frozen

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

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

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.

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.

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.

Human Chorionic Gonadotropin (hCG) Levels at Day 6

Blood tests were sent to a central laboratory to obtain hCG levels.

Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration

Blood tests were sent to a central laboratory to obtain progesterone levels.

Number of Live Births Resulting From the In Vitro Fertilization Process

Number of live births resulting from the IVF process

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.

Full Information

NCT ID

NCT00805935

First Posted

December 9, 2008

Last Updated

January 26, 2012

Sponsor

Ferring Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00805935

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2012

Overall Recruitment Status

Completed

Study Start Date

January 2009 (undefined)

Primary Completion Date

July 2010 (Actual)

Study Completion Date

September 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ferring Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Polycystic Ovarian Syndrome, Infertility

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

110 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Menotropin/Progesterone vaginal insert

Arm Type

Experimental

Arm Description

Arm Title

Menotropin/Progesterone in oil

Arm Type

Experimental

Arm Description

Arm Title

Follitropin beta/Progesterone vaginal insert

Arm Type

Active Comparator

Arm Description

Arm Title

Follitropin beta/Progesterone in oil

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Menotropin

Other Intervention Name(s)

Menopur®

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Progesterone vaginal insert

Other Intervention Name(s)

Endometrin®

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Follitropin beta

Other Intervention Name(s)

Follistim Pen®

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Progesterone in oil

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

leuprolide acetate

Other Intervention Name(s)

Lupron

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

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).

Time Frame

weeks 1-3

Secondary Outcome Measure Information:

Title

Number of Follicles Observed at Day 15

Description

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

Time Frame

approximately day 15

Title

Number of Oocytes Retrieved at Day 18

Description

Time Frame

approximately day 18

Title

Percentage of Oocytes Fertilized of the Total Number of Oocytes Retrieved

Description

The fertilization rate for each participant was the percentage of the number of oocytes inseminated of the total number of oocytes retrieved.

Time Frame

approximately day 19

Title

Number of Embryos Transferred at Three Stages of Development Before Implantation

Description

Time Frame

approximately day 24

Title

Number of Embryos Frozen

Description

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

Time Frame

approximately day 24

Title

Percentage of Participants With Biochemical Pregnancy at Approximately Day 38

Description

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

Time Frame

approximately day 38 (Day 14 post embryo transfer)

Title

Percentage of Participants With Clinical Pregnancy at Week 7

Description

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

Time Frame

approximately Day 52

Title

Percentage of Participants With Ongoing Pregnancy at Week 9

Description

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

Time Frame

approximately Day 65

Title

Estradiol Levels at Day 6

Description

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.

Time Frame

Day 6

Title

Human Chorionic Gonadotropin (hCG) Levels at Day 6

Description

Blood tests were sent to a central laboratory to obtain hCG levels.

Time Frame

Day 6

Title

Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration

Description

Blood tests were sent to a central laboratory to obtain progesterone levels.

Time Frame

approximately day 16

Title

Number of Live Births Resulting From the In Vitro Fertilization Process

Description

Number of live births resulting from the IVF process

Time Frame

Approximately 10 months

Title

Participants With Treatment Emergent Adverse Events

Description

Time Frame

Week 1 to week12

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

42 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Development Support

Organizational Affiliation

Ferring Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Conceptions Reproductive Associates of Colorado

City

Littleton

State/Province

Colorado

ZIP/Postal Code

80129

Country

United States

Facility Name

Women's Medical Research Group LLC, Florida

City

Clearwater

State/Province

Florida

ZIP/Postal Code

33759

Country

United States

Facility Name

Fertility Center of Illinois

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60610

Country

United States

Facility Name

Weill Cornell Medical College

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

Facility Name

Women & Infants' Hospital of RI

City

Providence

State/Province

Rhode Island

ZIP/Postal Code

02905

Country

United States

Facility Name

Center for Assisted Reproduction

City

Bedford

State/Province

Texas

ZIP/Postal Code

76022

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

25385669

Citation

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.

Results Reference

derived

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

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