Investigate Dose of Org 36286 to Initiate Multiple Follicular Growth in a Controlled Ovarian Hyperstimulation Protocol for IVF or IVF/ICSI (P07015)

NCT ID: NCT00702806

Last Updated: 2024-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-07-01
• Study Completion Date: 2002-10-15

Brief Summary

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, participants were converted to treatment with Puregon® 150 IU 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).

Detailed Description

This trial was made up of two stages with different designs and was conducted at 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 participants with Org 36286 120 μg, 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. Treatment of the first participants 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.

Conditions

Infertility; In Vitro Fertilization

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Org 36286 120 μg + Puregon® 150 IU

On Cycle Day 2 or Day 3, a single intra-abdominal injection of Org 36286 120 μg was administered to participants. On stimulation Day 8, a daily subcutaneous dose of Puregon® 150 IU was administered up to and including the time of Pregnyl® administration as a single dose of 10,000 IU subcutaneously. The maximum treatment duration of Puregon® 150 IU was 19 days. Orgalutran® 0.25 mg was administered subcutaneously once daily up to and including the day of Pregnyl®, when the leading follicle reached a size of \>= 14 mm.

Group Type: EXPERIMENTAL

Org 36286

Intervention Type: DRUG

Intra-abdominal injection of Org 36286

Puregon®

Intervention Type: DRUG

Subcutaneous Puregon® 150 IU

Orgalutran®

Intervention Type: DRUG

Subcutaneous Orgalutran® 0.25 mg

Pregnyl®

Intervention Type: DRUG

Subcutaneous Pregnyl® 10,000 IU

Org 36286 180 μg + Puregon® 150 IU

Cycle Day 2 or Day 3, a single intra-abdominal injection of Org 36286 180 μg was administered to participants. On stimulation Day 8, a daily subcutaneous dose of Puregon® 150 IU was administered up to and including the time of Pregnyl® administration as a single dose of 10,000 IU subcutaneously. The maximum treatment duration of Puregon® 150 IU was 19 days. Orgalutran® 0.25 mg was administered subcutaneously once daily up to and including the day of Pregnyl®, when the leading follicle reached a size of \>= 14 mm.

Group Type: EXPERIMENTAL

Org 36286

Intervention Type: DRUG

Intra-abdominal injection of Org 36286

Puregon®

Intervention Type: DRUG

Subcutaneous Puregon® 150 IU

Orgalutran®

Intervention Type: DRUG

Subcutaneous Orgalutran® 0.25 mg

Pregnyl®

Intervention Type: DRUG

Subcutaneous Pregnyl® 10,000 IU

Org 36286 240 μg + Puregon® 150 IU

Cycle Day 2 or Day 3, a single intra-abdominal injection of Org 36286 240 μg was administered to participants. On stimulation Day 8, a daily subcutaneous dose of Puregon® 150 IU was administered up to and including the time of Pregnyl® administration as a single dose of 10,000 IU subcutaneously. The maximum treatment duration of Puregon® 150 IU was 19 days. Orgalutran® 0.25 mg was administered subcutaneously once daily up to and including the day of Pregnyl®, when the leading follicle reached a size of \>= 14 mm.

Group Type: EXPERIMENTAL

Org 36286

Intervention Type: DRUG

Intra-abdominal injection of Org 36286

Puregon®

Intervention Type: DRUG

Subcutaneous Puregon® 150 IU

Orgalutran®

Intervention Type: DRUG

Subcutaneous Orgalutran® 0.25 mg

Pregnyl®

Intervention Type: DRUG

Subcutaneous Pregnyl® 10,000 IU

Puregon® 150 IU

On stimulation Day 8, a daily subcutaneous dose of Puregon® 150 IU was administered up to and including the time of Pregnyl® administration as a single dose of 10,000 IU subcutaneously. The maximum treatment duration of Puregon® 150 IU was 19 days. Orgalutran® 0.25 mg was administered subcutaneously once daily up to and including the day of Pregnyl®, when the leading follicle reached a size of \>= 14 mm.

Group Type: ACTIVE_COMPARATOR

Puregon®

Intervention Type: DRUG

Subcutaneous Puregon® 150 IU

Orgalutran®

Intervention Type: DRUG

Subcutaneous Orgalutran® 0.25 mg

Pregnyl®

Intervention Type: DRUG

Subcutaneous Pregnyl® 10,000 IU

Interventions

Org 36286

Intra-abdominal injection of Org 36286

Intervention Type: DRUG

Puregon®

Subcutaneous Puregon® 150 IU

Intervention Type: DRUG

Orgalutran®

Subcutaneous Orgalutran® 0.25 mg

Intervention Type: DRUG

Pregnyl®

Subcutaneous Pregnyl® 10,000 IU

Intervention Type: DRUG

Other Intervention Names

Corifollitropin alpha; recFSH; ganirelix (Ganirelix Acetate Injection); human chorionic gonadatropin; hCG

Eligibility Criteria

Inclusion Criteria

• Females of couples with an indication for COH and IVF or IVF/ICSI;
• Body mass index (BMI) >=18 and <=29 kg/m^2;
• Normal menstrual cycle length: 24-35 days;
• Ejaculatory sperm;

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Organon and Co

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Devroey P, Fauser BC, Platteau P, Beckers NG, Dhont M, Mannaerts BM. Induction of multiple follicular development by a single dose of long-acting recombinant follicle-Stimulating hormone (FSH-CTP, corifollitropin alfa) for controlled ovarian stimulation before in vitro fertilization. J Clin Endocrinol Metab. 2004 May;89(5):2062-70. doi: 10.1210/jc.2003-031766.

Reference Type: RESULT

PMID: 15126522 (View on PubMed)

Other Identifiers

38807

Identifier Type: -

Identifier Source: secondary_id

P07015

Identifier Type: -

Identifier Source: org_study_id