Investigate Dose of Org 36286 to Initiate Multiple Follicular Growth in a Controlled Ovarian Hyperstimulation Protocol for IVF or IVF/ICSI (Study 38807)(COMPLETED) - Full Text View

Sponsor:	Schering-Plough
Information provided by:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00702806

Purpose

The primary objective of this trial was to investigate the appropriate dose of a single injection of Org 36286 to initiate multifollicular growth for the first seven days in a controlled ovarian hyperstimulation (COH) protocol for IVF and IVF/ICSI. After seven days, patients were converted to treatment with 150 IU Puregon® and administration of the GnRH antagonist Orgalutran® to finalize the stimulation cycle. Secondary objectives were the safety (including the absence of antibody formation) and the direct effects of Org 36286 on reproductive functions (steroidogenesis, oocyte maturation, embryo quality and implantation).

Condition	Intervention	Phase
Infertility In Vitro Fertilization	Drug: Corifollitropin Alfa Drug: Puregon® Drug: Orgalutran®	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	A Phase II, Open Label, Prospective, Randomized, Comparative Clinical Trial to Investigate the Appropriate Dose of a Single Injection of Org 36286 (Corifollitropin Alfa) to Initiate Multiple Follicular Growth in a Controlled Ovarian Hyperstimulation Protocol for IVF or IVF/ICSI.

Resource links provided by NLM:

MedlinePlus related topics: Infertility

Drug Information available for: Urofollitropin Ganirelix Ganirelix acetate Follitropin beta Corifollitropin alfa

U.S. FDA Resources

Further study details as provided by Schering-Plough:

Primary Outcome Measures:

The primary endpoint for the study was the amount (IU) of Puregon® from Treatment Day 8 onwards to reach the criteria for the administration of hCG for induction of final oocyte maturation. [ Time Frame: One cycle ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Frequency and reason for cycle cancellation [ Time Frame: At time of cancellation ] [ Designated as safety issue: No ]
Number of cumulus-oocyte-complexes [ Time Frame: During one cycle ] [ Designated as safety issue: No ]
Number of good quality embryos [ Time Frame: During one cycle ] [ Designated as safety issue: No ]
Number of ongoing pregnancies [ Time Frame: 10 Weeks after hCG ] [ Designated as safety issue: No ]
anti-Org 36286 antibodies [ Time Frame: on Day 1 of treatment (just prior to the injection of Org 36286) and two weeks after embryo transfer ] [ Designated as safety issue: Yes ]
laboratory data [ Time Frame: at screening, on the day of hCG, and two weeks after embryo transfer ] [ Designated as safety issue: Yes ]
vital signs [ Time Frame: at screening, on the day of hCG, and two weeks after embryo transfer ] [ Designated as safety issue: Yes ]
occurrence and nature of (serious) adverse events [ Time Frame: End of trial ] [ Designated as safety issue: Yes ]

Enrollment:	104
Study Start Date:	July 2001
Study Completion Date:	October 2002
Primary Completion Date:	October 2002 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm 1: Experimental Single injection of 120 μg Org 36286, one week later fixed daily doses of 150 IU Puregon®	Drug: Corifollitropin Alfa On Cycle Day 2 (or 3), a single injection of 120, 180, or 240 ug Org 36286 was administered in the abdominal wall. From Stimulation Day 8 onwards treatment is continued with a daily SC dose of 150 IU recFSH up to and including the Day of hCG. The maximum total treatment duration is 19 days. Drug: Puregon® Starting on cycle day 2 (or 3), a fixed daily SC dose of Puregon will be administered for the entire stimulation period up to and including the day of hCG. The maximum total treatment duration is 19 days. Arms: Arm 4 Other Names: recFSH (Follistim AQ) Drug: Orgalutran® Orgalutran® (0.25 mg) SC once daily was given up to and including the day of hCG once the leading follicle reached a size of 14 mm
Arm 2: Experimental Single injection of 180 mcg Org 36286, one week later fixed daily doses of 150 IU Puregon®	Drug: Corifollitropin Alfa On Cycle Day 2 (or 3), a single injection of 120, 180, or 240 ug Org 36286 was administered in the abdominal wall. From Stimulation Day 8 onwards treatment is continued with a daily SC dose of 150 IU recFSH up to and including the Day of hCG. The maximum total treatment duration is 19 days. Drug: Puregon® Starting on cycle day 2 (or 3), a fixed daily SC dose of Puregon will be administered for the entire stimulation period up to and including the day of hCG. The maximum total treatment duration is 19 days. Arms: Arm 4 Other Names: recFSH (Follistim AQ) Drug: Orgalutran® Orgalutran® (0.25 mg) SC once daily was given up to and including the day of hCG once the leading follicle reached a size of 14 mm
Arm 3: Experimental Single injection of 240 μg Org 36286, one week later fixed daily doses of 150 IU Puregon®	Drug: Corifollitropin Alfa On Cycle Day 2 (or 3), a single injection of 120, 180, or 240 ug Org 36286 was administered in the abdominal wall. From Stimulation Day 8 onwards treatment is continued with a daily SC dose of 150 IU recFSH up to and including the Day of hCG. The maximum total treatment duration is 19 days. Drug: Puregon® Starting on cycle day 2 (or 3), a fixed daily SC dose of Puregon will be administered for the entire stimulation period up to and including the day of hCG. The maximum total treatment duration is 19 days. Arms: Arm 4 Other Names: recFSH (Follistim AQ) Drug: Orgalutran® Orgalutran® (0.25 mg) SC once daily was given up to and including the day of hCG once the leading follicle reached a size of 14 mm
Arm 4: Active Comparator Fixed daily dose of 150 IU Puregon®.	Drug: Puregon® Starting on cycle day 2 (or 3), a fixed daily SC dose of Puregon will be administered for the entire stimulation period up to and including the day of hCG. The maximum total treatment duration is 19 days. Arms: Arm 4 Other Names: recFSH (Follistim AQ) Drug: Orgalutran® Orgalutran® (0.25 mg) SC once daily was given up to and including the day of hCG once the leading follicle reached a size of 14 mm

Detailed Description:

This trial was made up of two stages with different designs and was conducted in two clinical trial sites.

Stage I was open-label and uncontrolled in a small cohort of women (n=6) to obtain first experience in employing Org 36286 in women meeting all inclusion and none of the exclusion criteria. Based on the results of a previous study, the most appropriate dose was anticipated to be 120 μg Org 36286, which was administered on Cycle Day 2 or 3. After seven days, treatment was continued with a fixed dose of 150 IU Puregon® SC. If the size of the leading follicle was >=14 mm, 0.25 mg Orgalutran® SC once daily was administered concurrently with 150 IU Puregon® up to and including the day of hCG. The maximum total treatment duration was 19 days. Treatment of the first two subjects with 120 μg Org 36286, that was expected to be adequate for COH, was cancelled due to disrupted follicular growth beyond Day 7. Therefore, the dose of Org 36286 was adapted from 120 μg to 180 µg as per amendment II. Treatment of the first subjects gave an indication of the validity of the anticipated doses to be used in Stage II, the actual dose-finding trial.

Stage II was open-label, prospective and randomized, comparing three experimental regimens differing in dose of Org 36286 (120 μg, 180 μg, or 240 μg) with a reference treatment.

Post-treatment assessments were completed at the visit two weeks after embryo transfer.

Eligibility

Ages Eligible for Study:	18 Years to 39 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Females of couples with an indication for COH and IVF or IVF/ICSI;
>=18 and <=39 years of age at the time of screening;
Body mass index (BMI) >=18 and <=29 kg/m^2;
Normal menstrual cycle length: 24-35 days;
Ejaculatory sperm;
Able and willing to sign informed consent

Exclusion Criteria:

History of/or current endocrine abnormality such as polycystic ovary syndrome (PCOS), or polycystic ovaries according to ultrasound scan (USS), (treated) hyperprolactinemia or evidence of ovarian dysfunction;
More than three unsuccessful COH cycles for IVF since the last established ongoing pregnancy (if applicable);
History of non- or low ovarian response to FSH/human menopausal gonadotropin (hMG) treatment;
Any clinically relevant hormone value outside the reference range during the early follicular phase (menstrual Cycle Day 2-7) as measured by the local laboratory (FSH, luteinizing hormone [LH], estradiol [E2], progesterone [P], total testosterone [T], thyroid stimulating hormone [TSH], and prolactin);
Any clinically relevant abnormal laboratory value;
Any ovarian and/or abdominal abnormality interfering with ultrasound examination;
Contraindications for the use of gonadotropins (e.g. tumors, pregnancy/lactation, undiagnosed vaginal bleeding, hypersensitivity, ovarian cysts);
Epilepsy, diabetes, cardiovascular, gastro-intestinal, hepatic, renal, pulmonary, or abdominal disease;
History or presence of alcohol or drug abuse within 12 months prior to signing informed consent;
Hypersensitivity to Orgalutran® or any of its components;
Administration of investigational drugs within three months prior to screening.
Use of hormonal preparations within one month prior to the start of Org 36286 with the exception of thyroid medication.

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	Schering-Plough ( Head, Clinical Trials Registry & Results Disclosure Group )
Study ID Numbers:	38807
Study First Received:	June 18, 2008
Last Updated:	October 2, 2009
ClinicalTrials.gov Identifier:	NCT00702806 History of Changes
Health Authority:	Belgium: Federal Agency for Medicinal Products and Health Products; Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Schering-Plough:

Pharmacological effects of drugs
Hormones
Hormone substitutes and Hormone Antagonists
Pharmacological Actions

Randomized
Milti-center
Multi-national

Additional relevant MeSH terms:

Infertility
Gonadal Disorders
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Endocrine System Diseases
Ovarian Diseases

Genital Diseases, Male
Pharmacologic Actions
Adnexal Diseases
Genital Diseases, Female
Ganirelix
Ovarian Hyperstimulation Syndrome

ClinicalTrials.gov processed this record on November 27, 2009