SJ-0021 (Gonalef®) Versus Purified Pituitary Gonadotropin (Fertinorm-P®) for Ovulation Induction in Japanese Infertile Women
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|ClinicalTrials.gov Identifier: NCT01185782|
Recruitment Status : Completed
First Posted : August 20, 2010
Results First Posted : February 24, 2012
Last Update Posted : December 27, 2013
|First Submitted Date ICMJE||August 11, 2010|
|First Posted Date ICMJE||August 20, 2010|
|Results First Submitted Date ICMJE||September 26, 2011|
|Results First Posted Date ICMJE||February 24, 2012|
|Last Update Posted Date||December 27, 2013|
|Study Start Date ICMJE||February 2007|
|Actual Primary Completion Date||December 2007 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||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)] ]
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.
|Original Primary Outcome Measures ICMJE
||Ovulation rate [ Time Frame: Assessment of ovulation on 6± 1 or 9 ± 1 days during Post-Treatment Assessment Period ]
The proportion of subjects who had ovulation among the evaluable subjects. Subjects are considered to have had ovulation if serum progesterone (P4) level > 5 ng/mL on 6± 1 or 9 ± 1 days during Post-Treatment Assessment Period, or if the subject dose not have such a P4 value but becomes clinical pregnant.
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||SJ-0021 (Gonalef®) Versus Purified Pituitary Gonadotropin (Fertinorm-P®) for Ovulation Induction in Japanese Infertile Women|
|Official Title ICMJE||Parallel-Group Comparative Study of SJ-0021 and Purified Pituitary Gonadotropin in Subjects With Amenorrhea I or Anovulatory Cycles - Phase III Single-Blind Study|
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.
Follicle stimulating hormone (FSH) is a heterodimeric glycoprotein wherein an alfa subunit and a beta subunit are noncovalently bonded. Follicle stimulating hormone is one of the key hormones regulating reproductive functions in both female and male mammals, including humans. In females, it stimulates the development of ovarian follicles, which carry oocytes, while in males it promotes spermatogenesis. Synthesis and secretion of FSH are stimulated by gonadotropin releasing hormone (GnRH), a hypothalamic peptide. Complete or partial deficiencies in FSH secretion are common causes of infertility in men and women. In women, this state is characterized by absence of ovulation or abnormal ovulation. In men, it leads to absence of or abnormally low production of spermatozoa. Administration of FSH, either alone or in combination with luteinizing hormone (LH), has been used successfully to treat these infertility problems. Until recently, only human menopausal gonadotropin (hMG), a mixture of human LH and FSH extracted from the urine of post-menopausal women, and purified FSH (u-hFSH), which could be used to reduce the LH content, had been available for treatment of infertility. In Japan, hMG and u-hFSH are still used to induce ovulation.
Purified pituitary gonadotropin, which was used as the comparator drug in this clinical trial, is a urinary gonadotropin preparation. However, it is not classified as hMG, but rather as a purified pituitary gonadotropin (u-hFSH), and is the preparation most commonly used in Japan. Since the LH content of u-hFSH is very low, it can be administered relatively safely, if adequate care is taken, to patients with polycystic ovary syndrome (PCOS). SJ-0021 is a recombinant human FSH (r-hFSH) that is produced using Chinese hamster ovary (CHO) cells as the host cells. The generic name for SJ-0021 is follitropin alfa for injection, and it is marketed overseas as GONAL-f®. It was approved in Japan in January 2006 as being effective in inducing spermatogenesis in cases of male hypogonadotropic hypogonadism (MHH).
This clinical trial comprised of a pretrial observation period, a treatment period [IMP administration period], and a post-treatment assessment period. The clinical trial was scheduled in such a way that spontaneous menstruation or withdrawal bleeding induced by progesterone administration occurred within 28 days after the completion of baseline tests conducted during the pretrial observation period. A visit to the trial site was then scheduled for any day between Day 2-5 of the spontaneous menstruation or withdrawal bleeding, during which actual registration of the subject for randomization and pre-administration tests were performed. After completion of pre-administration tests, 75 IU of either SJ-0021 or purified pituitary gonadotropin that was allocated to the subject was subcutaneously administered on the same day (dosing Day 1 of treatment period), and the same daily dose was maintained for the first 7 days of the treatment period. On dosing Day 8, the mean diameter of the dominant follicle was measured; if it was < 11 mm, the daily IMP dose was increased by 37.5 IU and this new daily dose was administered for the next 7 days. If the mean diameter of the dominant follicle was ≥ 11 mm but < 18 mm, the same (previous) IMP dose was administered for the next 7 days. If the mean diameter of the dominant follicle had already reached 18 mm or above, administration of the IMP was terminated, and the subject moved on to the post treatment assessment period. Similarly, if the mean diameter of the dominant follicle was < 11 mm on dosing Day 15 or Day 22, the dose was increased; if it was ≥ 11 mm but < 18 mm, administration was continued at the same previous dose, and if it was ≥ 18 mm IMP administration was terminated. The maximum dose of IMP that can be administered was 187.5 IU/day and the maximum dosing period for the IMP was 28 days. In addition to Day 8, Day 15 and Day 22, ultrasound examination can be conducted once or twice a week during the treatment period, based on the status of growth of the dominant follicle (and on every visit once the dominant follicle has achieved a maximum diameter of 16 mm).
Examinations for the first day of the post-treatment assessment period were conducted, as appropriate, on the day when the mean diameter of the dominant follicle reached ≥ 18 mm or on the day after dosing Day 28 of the IMP. The hCG cancellation criterion (i.e. four or more ovarian follicles with a mean diameter ≥ 16 mm) was also verified at the same time. If the hCG cancellation criterion was not met, a single dose of 5000 IU of hCG was administered intramuscularly, within 24 hours of the last ultrasound examination. Mid-luteal phase tests were conducted on Day 6 ± 1 and Day 9 ± 1 of the post-treatment assessment period, and a final examination was performed on Day 28-31 of the post-treatment assessment period. If the pregnancy test (urine) conducted at this final examination was positive, a further pregnancy test (ultrasound examination) was performed on Day 35-42 of the post-treatment assessment period.
On the other hand, if the mean diameter of the dominant follicle remained < 16 mm on the day after dosing Day 28 of the IMP, or the hCG cancellation criterion was met, hCG administration was withheld, and the examinations for the first day of the post-treatment assessment period as well as the final examination on Day 28-31 of the post-treatment assessment period were performed accordingly.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
|Study Arms ICMJE||
|Publications *||Taketani Y, Kelly E, Yoshimura Y, Hoshiai H, Irahara M, Mizunuma H, Saito H, Andoh K, Yanaihara T. Recombinant follicle-stimulating hormone (follitropin alfa) versus purified urinary follicle-stimulating hormone in a low-dose step-up regimen to induce ovulation in Japanese women with anti-estrogen-ineffective oligo- or anovulatory infertility: results of a single-blind Phase III study. Reprod Med Biol. 2010 Feb 23;9(2):99-106. doi: 10.1007/s12522-010-0046-5. eCollection 2010 Jun.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Actual Enrollment ICMJE
|Actual Study Completion Date ICMJE||December 2007|
|Actual Primary Completion Date||December 2007 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||20 Years to 39 Years (Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Japan|
|Removed Location Countries|
|NCT Number ICMJE||NCT01185782|
|Other Study ID Numbers ICMJE||IMP26648|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Merck KGaA, Darmstadt, Germany|
|Study Sponsor ICMJE||Merck KGaA, Darmstadt, Germany|
|Collaborators ICMJE||Merck Serono Co., Ltd., Japan|
|PRS Account||Merck KGaA, Darmstadt, Germany|
|Verification Date||December 2013|
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