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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-003227-38 | EudraCT Number |
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Study was terminated because of delays in sourcing replacement Investigational Medicinal Product for the study due to manufacturing delays.
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This is a prospective, multicenter, open-label, comparative and parallel-group study of ovulation induction evaluating tailoring of Recombinant follicle stimulating hormone (FSH) treatment using the Gonal-f® prefilled pen in World Health Organization (WHO) Type 2 anovulatory subjects who have previously failed to conceive with clomifene treatment.
Subjects will enter a screening period of up to one month before being randomized at the Baseline Visit, which will occur on Day 1 of the subject's menstrual cycle. Each subject will then receive up to 4 weeks treatment with Gonal-f®. If adequate follicular development (assessed by transvaginal ultrasound) is achieved, the subject will proceed to administration of human chorionic gonadotropin (hCG) within 24-48hrs of last Gonal-f® injection (or according to standard site practice).
Following administration of hCG, subjects will attempt to become pregnant via intercourse or intrauterine insemination. The method of conception will be determined by the subject's requirements and standard practice at the clinic site.
All subjects will be followed up appropriately until confirmation of biochemical pregnancy (hCG + minimum 14 days) and clinical pregnancy (hCG + minimum 42 days, for subjects with positive biochemical pregnancy test).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low Dose Gonal-f® Protocol | Experimental | Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. |
|
| Standard Low Dose Gonal-f® Protocol | Active Comparator | Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gonal-f® | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Cycles With Monofollicular Development | The monofollicular development was defined as the number of cycles with monofollicular development only one Follicle Greater Than or Equal (>= to 17 millimeter (mm) and no other follicles Greater than or equal to 14 mm following up to 4 weeks Gonal-f treatment. | Baseline up to 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Cycles With Bifollicular Development | The bifollicular development was defined as the number of cycles with bifollicular development of only two follicles greater than or equal to 17 millimeter. | Baseline up to 4 weeks |
| Percentage of Cycles With Multifollicular Development |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Serono Limited, UK | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Cork | Ireland | ||||
| Research Site |
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| ID | Title | Description |
|---|---|---|
| FG000 | Low Dose Gonal-f | Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. |
| FG001 | Standard Low Dose Gonal-f | Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent-to-Treat (ITT) included all subjects randomized and that had received at least 1 Gonal-f injection and had number of follicles measured at any point.
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| ID | Title | Description |
|---|---|---|
| BG000 | Low Dose Gonal-f | Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Percentage of Cycles With Monofollicular Development | The monofollicular development was defined as the number of cycles with monofollicular development only one Follicle Greater Than or Equal (>= to 17 millimeter (mm) and no other follicles Greater than or equal to 14 mm following up to 4 weeks Gonal-f treatment. | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | Baseline up to 4 weeks |
|
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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 | Low Dose Gonal-f | Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA 17.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
Study was terminated because of delays in sourcing replacement Investigational Medicinal Product (IMP) for the study due to manufacturing delays hence the outcome measure was not assessed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@merckgroup.com |
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| ID | Term |
|---|---|
| D007246 | Infertility |
| D016471 | Ovarian Hyperstimulation Syndrome |
| ID | Term |
|---|---|
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal 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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The multifollicular development was defined as the number of cycles with multifollicular development of three or more follicles greater than or equal to 14 millimeter |
| Baseline up to 4 weeks |
| Percentage of Ovulatory Cycles | Ovulation was defined as a serum progesterone (P4 ) level greater than or equal to 10 nanogram per milliliter (ng/mL) or Clinical Pregnancy. Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy. | Baseline up to 42 days post human chorionic gonadotrophin (hCG) administration |
| Percentage of Cycles Wherein Human Chorionic Gonadotropin (hCG) Was Not Administered | Baseline up to 4 weeks |
| Percentage of Cycles Resulting in Clinical Pregnancy | Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy. | 35-42 days post hCG administration |
| Number of Multiple Pregnancy | Multiple pregnancy is a pregnancy where more than one fetus develops simultaneously in the womb. There are two types of twinning-identical and fraternal. Identical twins represent the splitting of a single fertilized zygote (union of two gametes or male/female sex cells that produce a developing fetus) into two separate individuals. | 35-42 days post hCG administration |
| Number of Fetuses | 35-42 days post hCG administration |
| Number of Miscarriages After Confirmation of Clinical Pregnancy | Miscarriages were calculated per clinical pregnancy, and clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or confirmed by clinical signs of pregnancy. It excludes ectopic pregnancy. | 35-42 days post hCG administration |
| Number of Subjects With Ovarian Hyper Stimulation Syndrome (OHSS) | OHSS was defined as an exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations, classified as mild, moderate or severe according to the degree of abdominal distention, ovarian enlargement and respiratory, hemodynamic and metabolic complications. | up to 42 days post hCG administration |
| Duration of Recombinant Follicle Stimulating Hormone (rFSH) Stimulation | Baseline up to 4 weeks |
| Total Dose of Recombinant Follicle Stimulating Hormone (r-FSH) Administered Per Cycle | Baseline up to 4 weeks |
| Change From Baseline in Anti-Mullerian Hormone (AMH) Levels at Week 4 | Baseline, Week 4 |
| Testosterone Levels | Baseline |
| Sex Hormone Binding Globulin (SHBG) Levels | Baseline |
| Dublin |
| Ireland |
| Research Site | Galway | Ireland |
| Research Site | Cambridge | United Kingdom |
| Research site | Cheshunt | United Kingdom |
| Research Site | Derby | United Kingdom |
| Research Site | Edinburgh | United Kingdom |
| Research Site | Glasgow | United Kingdom |
| Research site | London | United Kingdom |
| Research Site | Nottingham | United Kingdom |
| BG001 | Standard Low Dose Gonal-f | Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Standard Low Dose Gonal-f | Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. |
|
| Secondary | Percentage of Cycles With Bifollicular Development | The bifollicular development was defined as the number of cycles with bifollicular development of only two follicles greater than or equal to 17 millimeter. | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | Baseline up to 4 weeks |
|
|
| Secondary | Percentage of Cycles With Multifollicular Development | The multifollicular development was defined as the number of cycles with multifollicular development of three or more follicles greater than or equal to 14 millimeter | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | Baseline up to 4 weeks |
|
|
| Secondary | Percentage of Ovulatory Cycles | Ovulation was defined as a serum progesterone (P4 ) level greater than or equal to 10 nanogram per milliliter (ng/mL) or Clinical Pregnancy. Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy. | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | Baseline up to 42 days post human chorionic gonadotrophin (hCG) administration |
|
|
| Secondary | Percentage of Cycles Wherein Human Chorionic Gonadotropin (hCG) Was Not Administered | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | Baseline up to 4 weeks |
|
|
| Secondary | Percentage of Cycles Resulting in Clinical Pregnancy | Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy. | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | 35-42 days post hCG administration |
|
|
| Secondary | Number of Multiple Pregnancy | Multiple pregnancy is a pregnancy where more than one fetus develops simultaneously in the womb. There are two types of twinning-identical and fraternal. Identical twins represent the splitting of a single fertilized zygote (union of two gametes or male/female sex cells that produce a developing fetus) into two separate individuals. | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | 35-42 days post hCG administration |
|
|
| Secondary | Number of Fetuses | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | 35-42 days post hCG administration |
|
|
| Secondary | Number of Miscarriages After Confirmation of Clinical Pregnancy | Miscarriages were calculated per clinical pregnancy, and clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or confirmed by clinical signs of pregnancy. It excludes ectopic pregnancy. | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | 35-42 days post hCG administration |
|
|
| Secondary | Number of Subjects With Ovarian Hyper Stimulation Syndrome (OHSS) | OHSS was defined as an exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations, classified as mild, moderate or severe according to the degree of abdominal distention, ovarian enlargement and respiratory, hemodynamic and metabolic complications. | Safety population included all subjects who were randomised and received at least 1 Gonal-f injection. | Posted | Number | subjects | up to 42 days post hCG administration |
|
|
|
| Secondary | Duration of Recombinant Follicle Stimulating Hormone (rFSH) Stimulation | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | Baseline up to 4 weeks |
|
|
| Secondary | Total Dose of Recombinant Follicle Stimulating Hormone (r-FSH) Administered Per Cycle | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | Baseline up to 4 weeks |
|
|
| Secondary | Change From Baseline in Anti-Mullerian Hormone (AMH) Levels at Week 4 | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | Baseline, Week 4 |
|
|
| Secondary | Testosterone Levels | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | Baseline |
|
|
| Secondary | Sex Hormone Binding Globulin (SHBG) Levels | Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall. | Posted | Baseline |
|
|
| 0 |
| 12 |
| 2 |
| 12 |
| EG001 | Standard Low Dose Gonal-f | Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. | 1 | 12 | 3 | 12 |
| Abdominal tenderness | Gastrointestinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Breast tenderness | Reproductive system and breast disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Vaginal discharge | Reproductive system and breast disorders | MedDRA 17.1 | Non-systematic Assessment |
|
Not provided
| D005831 |
| Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| 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 |