SJ-0021 (Gonalef®) Versus Purified Pituitary Gonadotropin (Fertinorm-P®) for Ovulation Induction in Japanese Infertile Women

This study has been completed.
Sponsor:
Collaborator:
Merck Serono Co., Ltd., Japan
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01185782
First received: August 11, 2010
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

Efficacy and safety studies in the past have suggested that a starting dose of 75 International Unit (IU) of SJ-0021, and an increase in the dose by 37.5 IU every 7 days, are safe for treatment of subjects with ovulatory disorders who are infertile due to hypothalamic or pituitary dysfunction and have amenorrhea I or anovulatory cycles (including oligomenorrhea and polymenorrhea).

This was a phase III, multicentre, single-blind, parallel-group comparative study conducted to provide confirmatory evidence of non-inferiority of SJ-0021 versus purified gonadotropin, a comparator drug, for induction of follicle development and ovulation in infertile Japanese women and to provide further information on the safety and tolerability of SJ-0021.


Condition Intervention Phase
Infertility
Ovulation Induction
Drug: Gonalef® (Follitropin alfa)
Drug: Purified pituitary gonadotropin (Fertinorm-P®)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Parallel-Group Comparative Study of SJ-0021 and Purified Pituitary Gonadotropin in Subjects With Amenorrhea I or Anovulatory Cycles - Phase III Single-Blind Study

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Percentage of Participants With Ovulation [ Time Frame: On Day 6±1 or 9±1 days during post-treatment assessment period (Day 35-42 of post-treatment period for clinical pregnancy)] ] [ Designated as safety issue: No ]
    Participants were considered to have ovulated if serum progesterone (P4) level was greater than or equal to 5 nanogram (ng)/mL on Day 6±1 or 9±1 during the post-treatment assessment period, or if the participant became clinically pregnant.


Secondary Outcome Measures:
  • Number of Participants With the Dominant Follicle Achieving 18 mm in Mean Diameter [ Time Frame: Start of treatment period until Day 1 of post-treatment assessment period ] [ Designated as safety issue: No ]
  • Time for Dominant Follicle to Achieve 18 mm in Mean Diameter [ Time Frame: Start of treatment period until Day 1 of post-treatment assessment period ] [ Designated as safety issue: No ]
    Dosing time length was calculated as number of days from the first administration of the IMP until the mean diameter of the dominant follicle was confirmed to have reached 18 mm.

  • Total Dose of the Investigational Medicinal Product (IMP) Administered to Participants With Dominant Follicle Achieving 18 mm in Mean Diameter [ Time Frame: Start of treatment period until Day 1 of post-treatment assessment period ] [ Designated as safety issue: No ]
    Total dose of IMP administered was defined as the cumulative dose administered from the start of treatment with IMP until the mean diameter of the dominant follicle reached 18 mm.

  • Human Chorionic Gonadotropin (hCG) Cancellation Rate [ Time Frame: Day 1 of post-treatment assessment period ] [ Designated as safety issue: No ]
    hCG cancellation criterion was defined as the presence of 4 or more ovarian follicles with a mean diameter greater than or equal to 16 mm. If the hCG cancellation criterion was met, the administration of hCG was withheld. Otherwise, a single intramuscular dose of hCG 5000 IU (Japanese Pharmacopoeia- JP) was administered within 24 hours of the last ultrasound examination.

  • Single Follicle Maturation Rate [ Time Frame: Start of treatment period until Day 1 of post-treatment assessment period ] [ Designated as safety issue: No ]
    Single follicle maturation was defined as the presence of the dominant follicle with a mean diameter of 18 mm or greater without concurrent presence of other follicles of 14 mm or larger in diameter.

  • Biochemical Pregnancy Rate [ Time Frame: Day 28-31 of post-treatment assessment period ] [ Designated as safety issue: No ]
    Biochemical pregnancy was defined as a positive pregnancy test (urinary beta-hCG test) on Day 28-31 of the post-treatment assessment period

  • Clinical Pregnancy Rate [ Time Frame: Day 35-42 of post-treatment assessment period ] [ Designated as safety issue: No ]
    Clinical pregnancy was defined as existence of at least one ultrasonography confirmed gestational sac in the uterus, with or without heartbeat.

  • Ovulation Rate, Where Ovulation is Defined as a Serum P4 Level Greater Than or Equal to 10 ng/mL or Clinical Pregnancy [ Time Frame: On Day 6±1 or 9±1 during post-treatment assessment period ] [ Designated as safety issue: No ]
    For this secondary endpoint, participants were considered to have ovulated if serum P4 level was more than or equal to 10 ng/mL on Day 6±1 or 9±1 during the post-treatment assessment period, or if the participant became clinically pregnant.

  • Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and AEs Leading to Study Drug Discontinuation [ Time Frame: Pretrial observation period to post-treatment assessment period (Days 35-42) ] [ Designated as safety issue: Yes ]
    AEs: Any untoward medical occurrence in the form of signs, clinically significant abnormalities in laboratory findings, diseases, symptoms, or worsening of complications. TEAEs: AEs that occur during treatment with the IMP. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. Participants who discontinued from the study due to AE were also recorded.

  • Number of Participants With OHSS [ Time Frame: Start of treatment period to post-treatment assessment period (Day 35-42) ] [ Designated as safety issue: Yes ]
    OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting.


Enrollment: 300
Study Start Date: February 2007
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SJ-0021 group Drug: Gonalef® (Follitropin alfa)
Subcutaneous administration of follitropin alfa at a dose of 75 IU/day was started on dosing Day 1 and the same daily dose was maintained for the first 7 days of the treatment period. Dose increment by 37.5 IU was permitted on dosing Day 8, Day 15 and Day 22 if the dosage increase criterion was met.
Other Names:
  • Gonalef®
  • follitropin alfa
  • recombinant human follicle-stimulating hormone
  • r-hFSH
  • SJ-0021
Active Comparator: Purified pituitary gonadotropin group Drug: Purified pituitary gonadotropin (Fertinorm-P®)
Subcutaneous administration of purified pituitary gonadotropin at a dose of 75 IU/day was started on dosing Day 1 and the same daily dose was maintained for the first 7 days of the treatment period. Dose increment by 37.5 IU was permitted on dosing Day 8, Day 15 and Day 22 if the dosage increase criterion was met.
Other Names:
  • Fertinorm-P®
  • purified urinary human follicle-stimulatin hormone
  • urofollitropin
  • u-hFSH

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   20 Years to 39 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women aged 20 to 39 years (inclusive) who hope to bear children
  • Subjects who failed to achieve ovulation or pregnancy despite 2 cycles or more of anti-estrogen therapies (clomiphene citrate, cyclofenil, etc.)
  • Subjects who exhibited withdrawal bleeding in a progesterone test (Includes spontaneous menstruation in subjects with anovulatory cycles.)
  • Subjects having a body mass index between 17.0 and 28.0 at the time of baseline tests
  • Subjects who voluntarily consented in writing to participate in the clinical trial

Exclusion Criteria:

  • Subjects with ovarian tumors
  • Subjects with ovarian enlargement not due to PCOS
  • Subjects with genitourinary hemorrhage of unknown cause
  • Subjects who were or may be pregnant, or who were lactating
  • Subjects with history of allergic reaction or hypersensitivity to gonadotropin
  • Subjects with dysfunction of heart, lungs, kidneys, or cardiovascular systems of Grade 2 or higher (in compliance with the Pharmaceutical and Medical Safety Bureau Notification Yakuan No. 80 [issued 29 June 1992])
  • Subjects with serum progesterone (P4) level ≥ 5 ng/mL in baseline tests
  • Subjects with malignant tumors
  • Subjects with uterine amenorrhea
  • Subjects with elevated levels of serum gonadotropin due to premature ovarian failure (FSH ≥ 20 mIU/mL)
  • Subjects who were infertile due to known adrenal or thyroid dysfunction
  • Subjects who were diagnosed as having hyperprolactinemia
  • Subjects who had been documented or suspected of having intracranial lesions (e.g., pituitary tumors)
  • Infertile subjects involving gynecological factors other than amenorrhea I or anovulatory cycles, and for whom ovulation induction therapy was found to be contraindicated
  • Subjects who had participated in another clinical study within 6 months prior to start of the IMP administration
  • Subjects who had been administered SJ-0021 in the past
  • Subjects whose participation in this clinical trial was otherwise deemed inappropriate by the investigator or sub-investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01185782

Locations
Japan
The University of Tokyo Hospital
Tokyo, Japan
Sponsors and Collaborators
Merck KGaA
Merck Serono Co., Ltd., Japan
Investigators
Study Director: Kimitoshi Takemura Merck Serono Co., Ltd., Japan
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01185782     History of Changes
Obsolete Identifiers: NCT00467480
Other Study ID Numbers: IMP26648
Study First Received: August 11, 2010
Results First Received: September 26, 2011
Last Updated: December 2, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Merck KGaA:
Infertility
Ovulation induction
Gonalef® (Follitropin alfa)
Purified pituitary gonadotropin (Fertinorm-P®)
gonadotropin
Reproductive technologies, assisted
Polycystic ovary syndrome

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Gonadotropins, Pituitary
Hormones
Follicle Stimulating Hormone
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Fertility Agents, Male
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 20, 2014