A Study of the Efficacy and Safety of Highly Purified Menotrophin Versus Recombinant Follitropin Alfa

• ClinicalTrials.gov Identifier: NCT00257556
• Recruitment Status: Completed
• First Posted: November 23, 2005
• Results First Posted: February 26, 2010
• Last Update Posted: February 26, 2010
• Sponsor: Ferring Pharmaceuticals
• Information provided by: Ferring Pharmaceuticals

Tracking Information

• First Submitted Date: November 22, 2005
• First Posted Date: November 23, 2005
• Results First Submitted Date: January 8, 2010
• Results First Posted Date: February 26, 2010
• Last Update Posted Date: February 26, 2010
• Study Start Date: October 2005
• Actual Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 12, 2010)

• Number of Participants With an Ongoing Pregnancy [ Time Frame: Approx week 13; 9 weeks or more after the 1st positive pregnancy test ]
  Number of participants who met human chorionic gonadotrophin (hCG) criterion, received an embryo transfer, tested positive with a serum pregnancy test 11-14 days after embryo transfer and had an ongoing pregnancy (defined as positive fetal heart action) at ≥ 9 weeks after the first positive pregnancy test.
• Percentage of Participants With an Ongoing Pregnancy [ Time Frame: Approx week 13; 9 weeks or more after the first positive pregnancy test ]
  Percentage of participants who had an ongoing pregnancy ≥ 9 weeks after the first positive pregnancy test, as indicated by positive fetal heart action.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: February 12, 2010)

• Participants With Varying Numbers of Follicles That Were Greater Than or Equal to 17 Millimeters [ Time Frame: Day 7 and, if appropriate, every 2 days thereafter (Days 9/11/13) ]
  The criterion for ovulation induction was three follicles ≥ 17 mm diameter as shown by pelvic ultrasound examination. Patients were assessed by pelvic ultrasound on the morning (prior to menotrophin or follitropin alfa administration) of Day 7 and, if appropriate, every 2 days thereafter (Days 9/11/13) until the criterion was met.
• Participants With Varying Numbers of Oocytes Retrieved [ Time Frame: Approximately study day 15 ]
  Number of participants with grouped by the number of oocytes retrieved. Oocytes were retrieved following ovulation induction by subcutaneous administration of human chorionic gonadotrophin (hCG) in the form of choriogonadotropin alfa at a dose of 250 micrograms once participants reached the criteria of at least three follicles with >= 17mm in diameter.
• Participants With Varying Numbers of Pronuclear Stage Oocytes [ Time Frame: Approximately study day 15 ]
  Number of participants with various groupings of pronuclear oocytes retrieved 16-20 hours after insemination.
• Participants With Varying Numbers of Embryos Transferred [ Time Frame: Approximately study day 17 ]
  Number of participants with various categories of numbers of embryos transferred.
• Participants With Varying Numbers of Embryos Frozen [ Time Frame: Approximately study day 17 ]
  Number of participants with different categories of number of embryos frozen.
• Mean Number of Days Stimulated With Gonadotrophins [ Time Frame: study days 1 - 13 ]
  Number of days stimulated with study drug until participant met the criteria for ovulation induction. Ovulation induction criteria is three follicles greater than or equal to 17 mm diameter as shown by pelvic ultrasound examination.
• Pregnancy Outcomes [ Time Frame: Approximately 10 months ]
  Long term follow-up to determine the outcome of the pregnancy.
• Mean Endometrial Thickness [ Time Frame: Day 7 or 9 or 11 or 13 ]
  Measurement performed on day of human chorionic gonadotrophin (hCG) administration/ovulation induction.
• Mean Estradiol Level [ Time Frame: Day 7 or 9 or 11 or 13 ]
  Measurement on day of human chorionic gonadotrophin (hCG) administration / ovulation induction.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of the Efficacy and Safety of Highly Purified Menotrophin Versus Recombinant Follitropin Alfa
• Official Title: A Prospective, Open Label, Randomised, Parallel Group, Comparative Pilot Study to Study the Efficacy and Safety of Highly Purified Menotrophin Versus Recombinant FSH (Follitropin Alfa) Administered Subcutaneously to Subfertile Female Patients Undergoing IVF Using Antagonist Downregulation
• Brief Summary: Prospective open label, randomised, parallel group, comparative pilot.
• Detailed Description: Ongoing pregnancy rate, defined as positive fetal heart action 9 weeks after the first positive pregnancy test. Number/diameter of follicles, number of oocytes retrieved, number of pronuclear oocytes (referred to as zygotes or pre-embryos in the UK), quality of pronuclear stage oocytes, number of embryos transferred, quality of embryos, number of frozen embryos, endometrial thickness and morphology on day of HCG administration, estradiol levels at day of HCG administration, implantation rate, number of days stimulated with gonadotrophins and number of ampoules used, clinical pregnancy rate at 6 weeks after the first positive pregnancy test, pregnancy outcome.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Infertility

Intervention

• Drug: Menotrophin
  150 IU Menotrophin daily subcutaneous injection for a maximum of 13 days. In the event of hyperstimulation, the dose was reduced to 75 IU daily.
  Other Names:

  • Menopur
  • hMG
  • highly purified menotrophin
• Drug: Follitropin alfa
  150 IU follitropin alfa daily by subcutaneous injection for a maximum of 13 days. In the event of hyperstimulation, the dose was reduced to 75 IU daily.
  Other Names:

  • rFSH
  • recombinant FSH

Study Arms

• Experimental: Menotrophin
  Intervention: Drug: Menotrophin
• Active Comparator: Follitropin alfa
  Intervention: Drug: Follitropin alfa

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 2, 2009): 80
• Original Enrollment (submitted: November 22, 2005): 72
• Actual Study Completion Date: April 2009
• Actual Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Female patients aged > or = 20 and < or = 35 years with a BMI of >18 and <32 kg/m2 who have received no more than two previous cycles of in vitro fertilisation (IVF) or other assisted reproductive technique (ART) and whose partners have normal sperm (according to WHO 1999 criteria).

Inclusion criteria:

• Signed informed consent;
• Subfertile premenopausal female patients eligible for IVF treatment;
• Aged >=20 and <=35 years;
• Body mass index of >18 and <32 kg/m2
• Normal endocrine assessment within the last 6 months;
• Normal pelvic ultrasound (showing two ovaries, no ovarian abnormalities and normal uterus) within the last 6 months;
• Receipt of no more than two previous cycles of IVF (or other ART);
• At least 3 consecutive ovulatory menstrual cycles of 24-35 days, and documented evidence of ovulatory cycles within the previous 12 months;
• No fertility-modifying treatment within the 3 months prior to this treatment cycle;
• Infertility attributable to or in association with either tubal factor, or unexplained causes;
• Sperm of partner classed as normal according to WHO 1999 criteria within the year prior to beginning therapy;
• Negative serum beta-HCG pregnancy test prior to beginning therapy;
• Clinically normal baseline haematology, clinical chemistry, and urinalysis parameter values, negative serum HBsAg and HIV antibody tests;
• Screening endocrine test results (estradiol, LH, FSH, progesterone, prolactin, TSH) in early follicular phase within the normal limits for the clinical laboratory.

Exclusion criteria

• Presence of any clinically relevant systemic disease(e.g. insulin- dependent diabetes mellitus);
• A history of or current endocrine disease, including polycystic ovary- like syndrome and hyperprolactinaemia;
• A history of coagulation disorders;
• Persistent ovarian cysts;
• Contraindications for the use of gonadotrophins or GnRH antagonists;
• A history of hypersensitivity to any of the constituents of the study medication or related compounds;
• Three or more previous cycles of IVF (or other ART);
• A history of alcohol abuse (more than 30 units per week on a regular basis);
• History of chemo- or radiotherapy;
• Currently breast-feeding, pregnant or with a contraindication to pregnancy;
• Diagnosed poor responders in prior IVF treatment;
• History of severe ovarian hyperstimulation syndrome (OHSS) (4 or 5) in former IVF treatment;
• Investigational drug within the 30 days prior to treatment;
• Any other condition or history that the investigator considers might increase the risk to the individual.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 20 Years to 35 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, United Kingdom

Administrative Information

• NCT Number: NCT00257556
• Other Study ID Numbers: FE999906 CS004 (PROSPECT); 2004-001307-35 ( Registry Identifier: EudraCT )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Clinical Development Support, Ferring Pharmaceuticals
• Original Responsible Party: Not Provided
• Current Study Sponsor: Ferring Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Development Support; Ferring Pharmaceuticals

• PRS Account: Ferring Pharmaceuticals
• Verification Date: February 2010