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This trial is investigating the efficacy and safety of highly purified human chorionic gonadotropin (HP-hCG) and recombinant human chorionic gonadotropin (rhCG) for triggering of final follicular maturation in women undergoing controlled ovarian stimulation
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HP-hCG IM | Experimental | highly purified human chorionic gonadotropin, intramuscularly (IM) |
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| HP-hCG SC | Experimental | highly purified human chorionic gonadotropin, subcutaneously (SC) |
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| rhCG | Active Comparator | recombinant human chorionic gonadotropin |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| highly purified human chorionic gonadotropin | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Oocytes Retrieved | Oocyte retrieval took place 36 h (±2h) after hCG administration. At oocyte retrieval the number of oocytes retrieved was recorded. | Approximately 36 hours after hCG administration |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Metaphase II (MII) Oocytes | Only applicable for insemination using intracytoplasmic sperm injection (ICSI). The MII oocytes were counted prior to insemination. | Prior to insemination (within 6 hours after oocyte retrieval) |
| Number of Fertilized (2 Pronuclei (2PN)) Oocytes |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Development Support | Ferring Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto Ideia Fértil de Saúde Reproductive (there may be other sites in this country) | São Paulo | Brazil |
In total 245 subjects were screened. Of these, 69 were screening failures and 176 were randomized. All randomized subjects were exposed to investigational medicinal product (IMP).
A total of 4 sites in Brazil randomized subjects to the trial.
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| ID | Title | Description |
|---|---|---|
| FG000 | HP-hCG IM | Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM) Highly purified human chorionic gonadotropin |
| FG001 | HP-hCG SC | Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC) Highly purified human chorionic gonadotropin |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 30, 2015 | Oct 12, 2018 |
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| recombinant human chorionic gonadotropin | Drug |
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Fertilization was assessed by counting the number of pronuclei, which was recorded as 0, 1, 2 or >2. Correct fertilization was defined as oocytes with 2PN. |
| One day after oocyte retrieval |
| Positive β Unit of Human Chorionic Gonadotropin (βhCG) Rate | Defined as percentage of subjects with positive beta hCG. A positive β hCG was confirmed by a blood test obtained 13-15 days after transfer. | 13-15 days after transfer |
| Clinical Pregnancy Rate | Defined as percentage of subjects with clinical pregnancy. Clinical pregnancy was defined as at least one gestational sac 5-6 weeks after transfer. | 5-6 weeks after transfer |
| Frequency of Adverse Events (AEs) | The number of treatment-emergent AEs (TEAEs) in each treatment group will be presented. | AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months. However, only TEAEs are presented |
| Intensity of AEs | The intensity of an TEAE would be classified using the following 3-point scale: mild (awareness of signs or symptoms, but no disruption of usual activity), moderate (event sufficient to affect usual activity [disturbing]) or severe (inability to work or perform usual activities [unacceptable]). | AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months. However, only TEAEs are presented. |
| FG002 | rhCG SC | Recombinant human chorionic gonadotropin 250 µg SC Recombinant human chorionic gonadotropin |
| COMPLETED |
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| NOT COMPLETED |
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The intention to treat (ITT) analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment. All relevant baseline data were summarized based on the ITT analysis set. The ITT analysis set included all 176 randomized subjects.
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| ID | Title | Description |
|---|---|---|
| BG000 | HP-hCG IM | Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM) Highly purified human chorionic gonadotropin |
| BG001 | HP-hCG SC | Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC) Highly purified human chorionic gonadotropin |
| BG002 | rhCG SC | Recombinant human chorionic gonadotropin 250 µg SC Recombinant human chorionic gonadotropin |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Oocytes Retrieved | Oocyte retrieval took place 36 h (±2h) after hCG administration. At oocyte retrieval the number of oocytes retrieved was recorded. | The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment. | Posted | Mean | Standard Deviation | Number of oocytes | Approximately 36 hours after hCG administration |
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| Secondary | Number of Metaphase II (MII) Oocytes | Only applicable for insemination using intracytoplasmic sperm injection (ICSI). The MII oocytes were counted prior to insemination. | The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment. Note that only subjects with ICSI were included in this analysis, i.e. 58 subjects in the HP-hCG IM group, 55 subjects in the HP-hCG SC group and 57 subjects in the rhCG SC group. | Posted | Mean | Standard Deviation | Number of MII oocytes | Prior to insemination (within 6 hours after oocyte retrieval) |
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| Secondary | Number of Fertilized (2 Pronuclei (2PN)) Oocytes | Fertilization was assessed by counting the number of pronuclei, which was recorded as 0, 1, 2 or >2. Correct fertilization was defined as oocytes with 2PN. | The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment. | Posted | Mean | Standard Deviation | Number of fertilized oocytes | One day after oocyte retrieval |
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| Secondary | Positive β Unit of Human Chorionic Gonadotropin (βhCG) Rate | Defined as percentage of subjects with positive beta hCG. A positive β hCG was confirmed by a blood test obtained 13-15 days after transfer. | The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment. | Posted | Number | percentage of participants | 13-15 days after transfer |
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| Secondary | Clinical Pregnancy Rate | Defined as percentage of subjects with clinical pregnancy. Clinical pregnancy was defined as at least one gestational sac 5-6 weeks after transfer. | The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment. | Posted | Number | percentage of participants | 5-6 weeks after transfer |
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| Secondary | Frequency of Adverse Events (AEs) | The number of treatment-emergent AEs (TEAEs) in each treatment group will be presented. | Safety was summarized based on the safety analysis set.The safety analysis set included all 176 subjects. Subjects were analyzed according to their actual treatment. | Posted | Number | Number of AEs | AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months. However, only TEAEs are presented |
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| Secondary | Intensity of AEs | The intensity of an TEAE would be classified using the following 3-point scale: mild (awareness of signs or symptoms, but no disruption of usual activity), moderate (event sufficient to affect usual activity [disturbing]) or severe (inability to work or perform usual activities [unacceptable]). | Safety was summarized based on the safety analysis set.The safety analysis set included all 176 subjects. Subjects were analyzed according to their actual treatment. | Posted | Count of Participants | Participants | AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months. However, only TEAEs are presented. |
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AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | HP-hCG IM | Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM) Highly purified human chorionic gonadotropin | 0 | 58 | 1 | 58 | 12 | 58 |
| EG001 | HP-hCG SC | Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC) Highly purified human chorionic gonadotropin | 0 | 58 | 1 | 58 | 12 | 58 |
| EG002 | rhCG | Recombinant human chorionic gonadotropin 250 µg SC Recombinant human chorionic gonadotropin | 0 | 60 | 2 | 60 | 11 | 60 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA 18.1 | Systematic Assessment |
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| Adnexal torsion | Reproductive system and breast disorders | MedDRA 18.1 | Systematic Assessment |
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| Ovarian hyperstimulation syndrome | Reproductive system and breast disorders | MedDRA 18.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Biochemical pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA 18.1 | Systematic Assessment |
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| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA 18.1 | Systematic Assessment |
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| Haemorrhage in pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA 18.1 | Systematic Assessment |
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| Vanishing twin syndrome | Pregnancy, puerperium and perinatal conditions | MedDRA 18.1 | Systematic Assessment |
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| Pelvic pain | Reproductive system and breast disorders | MedDRA 18.1 | Systematic Assessment |
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The only disclosure restriction on the Principal Investigator (PI) is that Sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the Sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Sponsor to seek patent protection of the invention.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Compliance | Ferring Pharmaceuticals | DK0-Disclosure@ferring.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 11, 2016 | Oct 12, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D007246 | Infertility |
| ID | Term |
|---|---|
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D006063 | Chorionic Gonadotropin |
| C412828 | Ovidrel |
| ID | Term |
|---|---|
| D006062 | Gonadotropins |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010926 | Placental Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011257 | Pregnancy Proteins |
| D011506 | Proteins |
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| 35-37 years |
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| >=38 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Mean number of oocytes retrieved for the treatment comparison of HP-hCG SC versus rhCG SC | Mean Difference (Final Values) | 0.8 | 2-Sided | 95 | -0.5 | 2.0 | ANOVA with treatment, stratum (<10 or ≥10 follicles with a diameter ≥12 mm), and site as fixed factors. | Non-Inferiority | As step 2 in the pre-specified sequential testing, NI was tested for HP-hCG SC compared to rhCG SC. |
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