Investigate Dose of Org 36286 to Initiate Multiple Follicular Growth in a Controlled Ovarian Hyperstimulation Protocol for IVF or IVF/ICSI (Study 38807)(COMPLETED)
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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 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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. |
- 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 ]
- 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 |
|---|---|
|
Experimental: Arm 1
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.
Other Name: Org 36286
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) 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
Other Name: ganirelix (Ganirelix Acetate Injection)
|
|
Experimental: Arm 2
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.
Other Name: Org 36286
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) 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
Other Name: ganirelix (Ganirelix Acetate Injection)
|
|
Experimental: Arm 3
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.
Other Name: Org 36286
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) 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
Other Name: ganirelix (Ganirelix Acetate Injection)
|
|
Active Comparator: Arm 4
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) 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
Other Name: ganirelix (Ganirelix Acetate Injection)
|
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 |
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 More Information
No publications provided
| Responsible Party: | Head, Clinical Trials Registry & Results Disclosure Group, Schering-Plough |
| ClinicalTrials.gov Identifier: | NCT00702806 History of Changes |
| Other Study ID Numbers: | 38807 |
| Study First Received: | June 18, 2008 |
| Last Updated: | October 2, 2009 |
| 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 Ovarian Hyperstimulation Syndrome Genital Diseases, Male Genital Diseases, Female Ovarian Diseases Adnexal Diseases Gonadal Disorders |
Endocrine System Diseases Ganirelix Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 22, 2013