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The overall objective of this trial is to compare the ovarian response in assisted reproductive technology (ART) subjects administered GONAL f® according to the 'Consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment' (CONSORT) calculator versus given a standard GONAL f® dose of 150 International Unit (IU) per day.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CONSORT Dosing | Experimental | GONAL-f® dose based on subject baseline characteristics determined according to the CONSORT calculator |
|
| Standard Dosing | Active Comparator | GONAL-f® at a standard dose of 150 IU per day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GONAL f® prefilled pen | Drug | GONAL f® doses starting at minimum of 112.5 IU per day and a maximum of 450 IU per day for 1 cycle only |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Oocytes Retrieved Per Participant | Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. | 34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU) |
| Measure | Description | Time Frame |
|---|---|---|
| Total GONAL-f® Dose | Start of treatment until end of stimulation cycle (approximately 28 days) | |
| Mean GONAL-f® Daily Dose | Start of treatment until end of stimulation cycle (approximately 28 days) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pablo Arriagada, MD | Merck Serono S.A., Geneva | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Geneva | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25596910 | Derived | Olivennes F, Trew G, Borini A, Broekmans F, Arriagada P, Warne DW, Howles CM. Randomized, controlled, open-label, non-inferiority study of the CONSORT algorithm for individualized dosing of follitropin alfa. Reprod Biomed Online. 2015 Mar;30(3):248-57. doi: 10.1016/j.rbmo.2014.11.013. Epub 2014 Dec 15. |
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A total of 244 participants gave informed consent and were screened for study entry. Forty-four (44) of these participants were not randomized due to: screening failure (38), failure to down regulate (3), or other reasons (3). A total of 200 participants were randomized to one of the two treatment arms.
Participants were enrolled at 22 clinical trial centers in 9 European countries and 1 center in Chile. Recruitment period: 29 August 2008 to 21 January 2010.
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| ID | Title | Description |
|---|---|---|
| FG000 | GONAL-f ® CONSORT Calculator | GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle. |
| FG001 | GONAL-f ® Standard Treatment | GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | GONAL-f ® CONSORT Calculator | GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 Per Participant | Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. | The modified Intention-To-Treat (ITT) population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received. | Posted | Mean | Standard Deviation | oocytes | 34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU) |
|
Adverse Events (AEs) were collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until the final treatment examination, on Day 15-20 of the post-treatment assessment period
Pre-Treatment:Medical conditions present at the initial study visit that did not worsen in severity or frequency during the study; Treatment-Emergent: If the onset date of the AE was on or after the first dose date of the study medication.
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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 | GONAL-f ® CONSORT Calculator | GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ovarian hyperstimulation syndrome | Reproductive system and breast disorders | MedDRA (Unspecified) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Serono, a division of Merck KGaA | +49-6151-72-5200 | service@merckgroup.com |
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| ID | Term |
|---|---|
| D007246 | Infertility |
| ID | Term |
|---|---|
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| C571801 | follitropin alfa |
| D015292 | Glycoprotein Hormones, alpha Subunit |
| ID | Term |
|---|---|
| D006063 | Chorionic Gonadotropin |
| D006062 | Gonadotropins |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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| GONAL f® prefilled pen | Drug | GONAL f® standard treatment arm (150 IU of GONAL f® per day) up to Day 5 of stimulation after which the dose can be adjusted based upon the subject's ovarian response and according to the center's standard practice. |
|
|
| Total Number of GONAL-f® Stimulation Treatment Days | Start of treatment until end of stimulation cycle (approximately 28 days) |
| Number of Participants With Cancelled Cycles Due to Excessive or Inadequate Response to Treatment | Number of participants with cancelled cycles due to excessive or inadequate response was evaluated. An excessive response: greater than or equal to 25 oocytes which could put the participant at risk of OHSS; An inadequate response: defined as 3 or less follicles of greater than or equal to 12 millimeter (mm) developing following at least 7 days of GONAL-f® treatment. | Start of treatment until Day 15-20 post-hCG |
| Percentage of Participants With Biochemical Pregnancies | Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum and that does not develop into a clinical pregnancy. | Start of treatment until Day 15-20 Post-hCG |
| Number of Participants With Fetal Sacs and Fetal Hearts | Number of participants with fetal sacs and fetal hearts (with activity) as seen on an ultrasound scan to confirm clinical pregnancy. | Day 35-42 Post-hCG |
| Implantation Rate | Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100. | Day 35-42 Post-hCG |
| Number of Participants With Multiple Pregnancies | Multiple pregnancy was defined as 2 or more fetal hearts with activity. | Day 35-42 Post-hCG |
| Serum Progesterone (P4) Levels | End of stimulation cycle (approximately 28 days) |
| Percentage of Participants With Clinical Pregnancy | Clinical pregnancy is defined by the number of sacs and hearts with activity per ultrasound scan performed on Day 35-42 post-hCG. | Day 35-42 Post-hCG |
| Number of Participants With OHSS | OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. | Start of treatment until Day 15-20 Post-hCG |
| Pregnancy Outcome - Number of Participants With Pregnancy and Their Outcome | Pregnancy outcomes are live outcome (live infant) and non-live outcome (non-live infant) or unknown outcome (subject lost to follow-up). | up to 9 month (following the end of treatment) |
| Lack of ovarian response to stimulation |
|
| Ovarian hyperstimulation syndrome (OHSS) |
|
| No fertilization |
|
| All embryos discarded |
|
| No embryo cleavage |
|
| BG001 | GONAL-f ® Standard Treatment | GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Number of participants analyzed (N) = 86 and 93 for GONAL-f® CONSORT calculator and GONAL-f® standard treatment arm group respectively at screening. | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Serum Anti-Mullerian Hormone (AMH) | Number of participants analyzed (N) = 86 and 93 for GONAL-f® CONSORT calculator and GONAL-f® standard treatment arm group respectively at screening. | Mean | Standard Deviation | nanogram/milliliter (ng/mL) |
|
| Serum Progesterone (P4) | Number of participants analyzed (N) = 86 and 93 for GONAL-f® CONSORT calculator and GONAL-f® standard treatment arm group respectively at screening. | Mean | Standard Deviation | nanomole/liter (nmol/L) |
|
| OG001 | GONAL-f ® Standard Treatment | GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice. |
|
|
|
| Secondary | Total GONAL-f® Dose | The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received. | Posted | Mean | Standard Deviation | IU | Start of treatment until end of stimulation cycle (approximately 28 days) |
|
|
|
|
| Secondary | Mean GONAL-f® Daily Dose | The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received. | Posted | Mean | Standard Deviation | IU | Start of treatment until end of stimulation cycle (approximately 28 days) |
|
|
|
|
| Secondary | Total Number of GONAL-f® Stimulation Treatment Days | The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received. | Posted | Mean | Standard Deviation | days | Start of treatment until end of stimulation cycle (approximately 28 days) |
|
|
|
|
| Secondary | Number of Participants With Cancelled Cycles Due to Excessive or Inadequate Response to Treatment | Number of participants with cancelled cycles due to excessive or inadequate response was evaluated. An excessive response: greater than or equal to 25 oocytes which could put the participant at risk of OHSS; An inadequate response: defined as 3 or less follicles of greater than or equal to 12 millimeter (mm) developing following at least 7 days of GONAL-f® treatment. | All the randomized participants were analyzed for this outcome measure (N=200). | Posted | Number | Participants | Start of treatment until Day 15-20 post-hCG |
|
|
|
| Secondary | Percentage of Participants With Biochemical Pregnancies | Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum and that does not develop into a clinical pregnancy. | The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received. | Posted | Number | percentage of participants | Start of treatment until Day 15-20 Post-hCG |
|
|
|
|
| Secondary | Number of Participants With Fetal Sacs and Fetal Hearts | Number of participants with fetal sacs and fetal hearts (with activity) as seen on an ultrasound scan to confirm clinical pregnancy. | The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received. | Posted | Number | participants | Day 35-42 Post-hCG |
|
|
|
| Secondary | Implantation Rate | Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100. | The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received. | Posted | Mean | Standard Deviation | percent sacs per embryo | Day 35-42 Post-hCG |
|
|
|
|
| Secondary | Number of Participants With Multiple Pregnancies | Multiple pregnancy was defined as 2 or more fetal hearts with activity. | The modified ITT population. Number of participants analyzed (N) signifies those participants who were evaluated for this outcome measure. | Posted | Number | participants | Day 35-42 Post-hCG |
|
|
|
| Secondary | Serum Progesterone (P4) Levels | The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received. | Posted | Mean | Standard Deviation | nmol/L | End of stimulation cycle (approximately 28 days) |
|
|
|
|
| Secondary | Percentage of Participants With Clinical Pregnancy | Clinical pregnancy is defined by the number of sacs and hearts with activity per ultrasound scan performed on Day 35-42 post-hCG. | The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received. | Posted | Number | percentage of participants | Day 35-42 Post-hCG |
|
|
|
|
| Secondary | Number of Participants With OHSS | OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. | Safety population included all the participants who were randomized. | Posted | Number | participants | Start of treatment until Day 15-20 Post-hCG |
|
|
|
| Secondary | Pregnancy Outcome - Number of Participants With Pregnancy and Their Outcome | Pregnancy outcomes are live outcome (live infant) and non-live outcome (non-live infant) or unknown outcome (subject lost to follow-up). | The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received. | Posted | Number | participants | up to 9 month (following the end of treatment) |
|
|
|
| 4 |
| 96 |
| 40 |
| 96 |
| EG001 | GONAL-f ® Standard Treatment | GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice. | 3 | 104 | 48 | 104 |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Adnexa uteri pain | Reproductive system and breast disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Ovarian hyperstimulation syndrome | Reproductive system and breast disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
The PI shall submit any results communication to the sponsor for review and comment at least 30 business days prior to submission. The sponsor shall have the right to request the PI to delete or modify any of sponsor's proprietary information contained therein. If the PI does not agree to the deletion or appropriate modification of such information, it shall postpone submission for publication or presentation for 60 days from the date the PI notifies the sponsor.
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D005640 | Follicle Stimulating Hormone |
| D006065 | Gonadotropins, Pituitary |
| D007986 | Luteinizing Hormone |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D013972 | Thyrotropin |
| D010926 | Placental Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| 1 (fetal sacs) |
|
| 2 (fetal sacs) |
|
| 3 (fetal sacs) |
|
| 0 (fetal hearts) |
|
| 1 (fetal hearts) |
|
| 2 (fetal hearts) |
|
| 3 (fetal hearts) |
|
| Unknown outcomes |
|