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Safety and Efficacy of Pre-defined, Fixed Dose of Gonal-f Pen Based on Subject Baseline Characteristics in Subjects Undergoing in Vitro Fertilization (IVF) (CONSORT)

Primary Purpose

Infertility

Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Gonal-f
Recombinant human chorionic gonadotrophin (r-hCG)
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertility focused on measuring Assisted Reproductive Technology (ART), Infertility, Ovarian stimulation

Eligibility Criteria

18 Years - 34 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria Be an infertile subject justifying an in-vitro fertilization/embryo transfer (IVF/ET) treatment. Have a male partner with semen analysis within the past six months prior to study entry considered adequate to proceed with regular insemination or intracytoplasmic sperm injection (ICSI) according to the center's standard practice. If these criteria are not met, the subject can only be entered if donor sperm will be used. Be between her 18th and 35th birthday (35 not included). Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length. Have early follicular phase (Day 2-4) serum levels within the last 3 months prior to study entry of: Follicle stimulating hormone (FSH) greater than or equal to (>=) 12 International units per liter (IU/L), and Oestradiol (E2) within center's local normal laboratory range values. Presence of both ovaries. Have a uterine cavity without abnormalities, which, in the investigator's opinion, could impair embryo implantation or pregnancy evolution as assessed within the last 3 years using ultrasound (US), hysteroscopy (HSC), or hysterosalpingography (HSG). Have a negative cervical papanicolaou (PAP) test within the last 6 months prior to study entry. Have at least one wash-out cycle (defined as >= 30 days since the last dose of clomiphene citrate or gonadotrophin treatment) since the last ART cycle and/or clomiphene citrate or gonadotrophin treatment prior to starting gonadotrophin releasing hormone (GnRH) agonist therapy. Have a negative pregnancy test prior to beginning GnRH agonist therapy. Be willing and able to comply with the protocol for the duration of the study. Have given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to her future medical care. Exclusion Criteria: Had 2 previous ART cycles with a poor response to gonadotrophin stimulation, defined as less than or equal to (<=) 5 mature follicles and/or <=3 oocytes collected in any previous IVF cycle or hyper response, defined as >=25 oocytes retrieved. Any medical condition, which in the judgement of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug. In case of doubt, the subject in question should be discussed with Serono's Therapeutic Director. Had previous severe ovarian hyperstimulation syndrome (OHSS). A body mass index (BMI) greater than (>) 30 kilogram per square meter (kg/m^2) Any contraindication to being pregnant and/or carrying a pregnancy to term. Extra-uterine pregnancy within the last 3 months. History of 3 or more miscarriages (early or late miscarriages) due to any cause. Tumours of the hypothalamus and pituitary gland. Ovarian enlargement or cyst of unknown aetiology. Ovarian, uterine or mammary cancer. A clinically significant systemic disease. Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus. Abnormal gynaecological bleeding of undetermined origin. Known allergy or hypersensitivity to human gonadotrophin preparations. Any active substance abuse or history of drug, medication or alcohol abuse in the past 5 years. Entered previously into this study or simultaneous participation in another clinical trial

Sites / Locations

  • Medical Information

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Gonal-f 112.5 IU

Gonal-f 37.5 IU

Gonal-f 75 IU

Gonal-f 150 IU

Gonal-f 187.5 IU

Gonal-f 225 IU

Gonal-f 262.5 IU

Gonal-f 300 IU

Arm Description

Outcomes

Primary Outcome Measures

Number of Oocytes Retrieved
Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval was a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.

Secondary Outcome Measures

Total Dose of Recombinant Human Follicle Stimulating Hormone (r-hFSH)
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Mean Number of Ovarian Stimulation Days
The mean number of stimulation days were determined based on the treatment administration information collected in the case report form. Ovarian stimulation included time from first r-hFSH injection (stimulation Day) until day on which r-hCG was administered (r-hCG day). As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Percentage of Cycles Cancelled Due to Excessive or Inadequate Response to r-hFSH
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Number of Subjects Needing Dose Adjustment
Number of subjects needing increase in dose, decrease in dose or increase and decrease both in dose were reported. As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Mean Daily Recombinant Human Follicle Stimulating Hormone (r-hFSH) Dose
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Embryo Implantation Rate
Embryo implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100. As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Overall Pregnancy Rate, Clinical Rate and Multiple Pregnancy Rate
Overall pregnancy rate was defined as the percentage of subjects with serum beta-hCG levels greater than 10 IU/L. Clinical pregnancy rate was defined as the percentage of subjects with at least 1 ultrasound confirmed gestational sac, with or without foetal heart activity. Multiple pregnancy rate was defined as the percentage of subjects with more than 1 ultrasound confirmed gestational sac in the uterus with fetal heart activity. As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.

Full Information

First Posted
November 4, 2005
Last Updated
August 29, 2017
Sponsor
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT00249834
Brief Title
Safety and Efficacy of Pre-defined, Fixed Dose of Gonal-f Pen Based on Subject Baseline Characteristics in Subjects Undergoing in Vitro Fertilization (IVF)
Acronym
CONSORT
Official Title
A Phase IIIB/IV, Open Label Study to Assess the Efficacy and Safety of a Pre-defined, Fixed Dose of Gonal-f® (Filled-by-Mass in a Prefilled Pen) Based on Subject Baseline Characteristics, for Ovarian Stimulation in Subjects Undergoing in Vitro Fertilization (IVF)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
September 22, 2004 (Actual)
Primary Completion Date
January 16, 2006 (Actual)
Study Completion Date
January 16, 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany

4. Oversight

5. Study Description

Brief Summary
Clinical validation of the assisted reproductive technology (ART) treatment guidelines, which determine the optimal dose of recombinant human follicle stimulating hormone (r-hFSH) based on subject baseline characteristics/predictors of ovarian response.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility
Keywords
Assisted Reproductive Technology (ART), Infertility, Ovarian stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
166 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gonal-f 112.5 IU
Arm Type
Experimental
Arm Title
Gonal-f 37.5 IU
Arm Type
Experimental
Arm Title
Gonal-f 75 IU
Arm Type
Experimental
Arm Title
Gonal-f 150 IU
Arm Type
Experimental
Arm Title
Gonal-f 187.5 IU
Arm Type
Experimental
Arm Title
Gonal-f 225 IU
Arm Type
Experimental
Arm Title
Gonal-f 262.5 IU
Arm Type
Experimental
Arm Title
Gonal-f 300 IU
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Gonal-f
Other Intervention Name(s)
follitropin alfa, Recombinant Human Follicle Stimulating Hormone (r-hFSH)
Intervention Description
GONAL-f (follitropin alfa) will be administered subcutaneously based on ART treatment guidelines, which determined the optimal dose of r-hFSH based on subject baseline characteristics/predictors of ovarian response throughout stimulation cycle.
Intervention Type
Drug
Intervention Name(s)
Recombinant human chorionic gonadotrophin (r-hCG)
Intervention Description
When at least 1 follicle greater than or equal to (>=) 18 millimeter (mm) and 2 follicles >=16 mm in diameter develop, 250 microgram (mcg) of recombinant human chorionic gonadotrophin (r-hCG) will be administered.
Primary Outcome Measure Information:
Title
Number of Oocytes Retrieved
Description
Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval was a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Time Frame
Ovum pick up day (34 to 38 hours post r-hCG administration)
Secondary Outcome Measure Information:
Title
Total Dose of Recombinant Human Follicle Stimulating Hormone (r-hFSH)
Description
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Time Frame
up to end of stimulation cycle (approximately 31 days)
Title
Mean Number of Ovarian Stimulation Days
Description
The mean number of stimulation days were determined based on the treatment administration information collected in the case report form. Ovarian stimulation included time from first r-hFSH injection (stimulation Day) until day on which r-hCG was administered (r-hCG day). As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Time Frame
up to end of stimulation cycle (approximately 31 days)
Title
Percentage of Cycles Cancelled Due to Excessive or Inadequate Response to r-hFSH
Description
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Time Frame
up to end of stimulation cycle (approximately 31 days)
Title
Number of Subjects Needing Dose Adjustment
Description
Number of subjects needing increase in dose, decrease in dose or increase and decrease both in dose were reported. As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Time Frame
6 days post r-hFSH treatment
Title
Mean Daily Recombinant Human Follicle Stimulating Hormone (r-hFSH) Dose
Description
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Time Frame
up to end of stimulation cycle (approximately 31 days)
Title
Embryo Implantation Rate
Description
Embryo implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100. As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Time Frame
35-42 days post r-hCG administration
Title
Overall Pregnancy Rate, Clinical Rate and Multiple Pregnancy Rate
Description
Overall pregnancy rate was defined as the percentage of subjects with serum beta-hCG levels greater than 10 IU/L. Clinical pregnancy rate was defined as the percentage of subjects with at least 1 ultrasound confirmed gestational sac, with or without foetal heart activity. Multiple pregnancy rate was defined as the percentage of subjects with more than 1 ultrasound confirmed gestational sac in the uterus with fetal heart activity. As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
Time Frame
35-42 days post r-hCG administration

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
34 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Be an infertile subject justifying an in-vitro fertilization/embryo transfer (IVF/ET) treatment. Have a male partner with semen analysis within the past six months prior to study entry considered adequate to proceed with regular insemination or intracytoplasmic sperm injection (ICSI) according to the center's standard practice. If these criteria are not met, the subject can only be entered if donor sperm will be used. Be between her 18th and 35th birthday (35 not included). Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length. Have early follicular phase (Day 2-4) serum levels within the last 3 months prior to study entry of: Follicle stimulating hormone (FSH) greater than or equal to (>=) 12 International units per liter (IU/L), and Oestradiol (E2) within center's local normal laboratory range values. Presence of both ovaries. Have a uterine cavity without abnormalities, which, in the investigator's opinion, could impair embryo implantation or pregnancy evolution as assessed within the last 3 years using ultrasound (US), hysteroscopy (HSC), or hysterosalpingography (HSG). Have a negative cervical papanicolaou (PAP) test within the last 6 months prior to study entry. Have at least one wash-out cycle (defined as >= 30 days since the last dose of clomiphene citrate or gonadotrophin treatment) since the last ART cycle and/or clomiphene citrate or gonadotrophin treatment prior to starting gonadotrophin releasing hormone (GnRH) agonist therapy. Have a negative pregnancy test prior to beginning GnRH agonist therapy. Be willing and able to comply with the protocol for the duration of the study. Have given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to her future medical care. Exclusion Criteria: Had 2 previous ART cycles with a poor response to gonadotrophin stimulation, defined as less than or equal to (<=) 5 mature follicles and/or <=3 oocytes collected in any previous IVF cycle or hyper response, defined as >=25 oocytes retrieved. Any medical condition, which in the judgement of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug. In case of doubt, the subject in question should be discussed with Serono's Therapeutic Director. Had previous severe ovarian hyperstimulation syndrome (OHSS). A body mass index (BMI) greater than (>) 30 kilogram per square meter (kg/m^2) Any contraindication to being pregnant and/or carrying a pregnancy to term. Extra-uterine pregnancy within the last 3 months. History of 3 or more miscarriages (early or late miscarriages) due to any cause. Tumours of the hypothalamus and pituitary gland. Ovarian enlargement or cyst of unknown aetiology. Ovarian, uterine or mammary cancer. A clinically significant systemic disease. Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus. Abnormal gynaecological bleeding of undetermined origin. Known allergy or hypersensitivity to human gonadotrophin preparations. Any active substance abuse or history of drug, medication or alcohol abuse in the past 5 years. Entered previously into this study or simultaneous participation in another clinical trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Medical Information
City
Paris
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
19192339
Citation
Olivennes F, Howles CM, Borini A, Germond M, Trew G, Wikland M, Zegers-Hochschild F, Saunders H, Alam V; CONSORT study group. Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study. Reprod Biomed Online. 2009 Feb;18(2):195-204. doi: 10.1016/s1472-6483(10)60256-8.
Results Reference
background
PubMed Identifier
21575853
Citation
Olivennes F, Howies CM, Borini A, Germond M, Trew G, Wikland M, Zegers-Hochschild F, Saunders H, Alam V. Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study. Reprod Biomed Online. 2011 Feb;22 Suppl 1:S73-82. doi: 10.1016/S1472-6483(11)60012-6.
Results Reference
result
Links:
URL
http://www.fertilitylifelines.com
Description
Full FDA approved prescribing information can be found here

Learn more about this trial

Safety and Efficacy of Pre-defined, Fixed Dose of Gonal-f Pen Based on Subject Baseline Characteristics in Subjects Undergoing in Vitro Fertilization (IVF)

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