AS900672-Enriched in Ovulation Induction

NCT ID: NCT00553514

Last Updated: 2014-02-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2009-03-31

Brief Summary

This is a Phase 2, interventional, multi-center, randomized, assessor-blind, active-comparator, dose-finding study to evaluate a new investigational long-acting follicle stimulating hormone (FSH) in oligo-anovulatory women undergoing ovulation induction (OI). This study will compare 4 doses of the investigational drug versus a currently marketed drug follitropin alfa (Gonal-f ®) prefilled pen with regards to ovulation rate.

Detailed Description

The study was terminated after Merck Serono had taken the decision not to pursue the development of AS900672-enriched in ovulation induction (OI). This decision was not related to any safety or efficacy concerns over the use of AS900672-Enriched in OI.

Conditions

Ovulation Induction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

AS900672-Enriched 10 mcg

Group Type: EXPERIMENTAL

AS900672-Enriched 10 microgram (mcg)

Intervention Type: DRUG

Single injection of AS900672-Enriched (hyperglycosylated recombinant human follicle stimulating hormone \[r-hFSH\]), 10 mcg will be administered subcutaneously on Stimulation Day 1 (S1). Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Follitropin alfa 75 international unit (IU)

Intervention Type: DRUG

Follitropin alfa (Gonal-f®) 75 IU will be administered subcutaneously once daily from S1 up to Stimulation Day 14 (S14) based upon ovarian response, until recombinant human chorionic gonadotropin (r-hCG) administration day. Subjects who will be receiving AS900672-Enriched 10, 20, 30 and 40 mcg will also receive daily dose of follitropin alfa 75 IU subcutaneously from Stimulation Day 7 (S7) up to S14. Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Recombinant human chorionic gonadotropin (r-hCG)

Intervention Type: DRUG

Recombinant human chorionic gonadotropin (r-hCG) will be administered as a single dose of 250 mcg subcutaneously, when follicular response is adequate (that is, less than or equal to \[=\<\] 3 follicles with a mean diameter of greater than or equal to \[\>=\] 14 millimeter \[mm\], and one or two of these follicles with a diameter of \>= 17 mm).

AS900672-Enriched 20 mcg

Group Type: EXPERIMENTAL

AS900672-Enriched 20 mcg

Intervention Type: DRUG

Single injection of AS900672-Enriched (hyperglycosylated r-hFSH), 20 mcg will be administered subcutaneously on S1. Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Follitropin alfa 75 international unit (IU)

Intervention Type: DRUG

Follitropin alfa (Gonal-f®) 75 IU will be administered subcutaneously once daily from S1 up to Stimulation Day 14 (S14) based upon ovarian response, until recombinant human chorionic gonadotropin (r-hCG) administration day. Subjects who will be receiving AS900672-Enriched 10, 20, 30 and 40 mcg will also receive daily dose of follitropin alfa 75 IU subcutaneously from Stimulation Day 7 (S7) up to S14. Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Recombinant human chorionic gonadotropin (r-hCG)

Intervention Type: DRUG

Recombinant human chorionic gonadotropin (r-hCG) will be administered as a single dose of 250 mcg subcutaneously, when follicular response is adequate (that is, less than or equal to \[=\<\] 3 follicles with a mean diameter of greater than or equal to \[\>=\] 14 millimeter \[mm\], and one or two of these follicles with a diameter of \>= 17 mm).

AS900672-Enriched 30 mcg

Group Type: EXPERIMENTAL

AS900672-Enriched 30 mcg

Intervention Type: DRUG

Single injection of AS900672-Enriched (hyperglycosylated r-hFSH), 30 mcg will be administered subcutaneously on S1. Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Follitropin alfa 75 international unit (IU)

Intervention Type: DRUG

Follitropin alfa (Gonal-f®) 75 IU will be administered subcutaneously once daily from S1 up to Stimulation Day 14 (S14) based upon ovarian response, until recombinant human chorionic gonadotropin (r-hCG) administration day. Subjects who will be receiving AS900672-Enriched 10, 20, 30 and 40 mcg will also receive daily dose of follitropin alfa 75 IU subcutaneously from Stimulation Day 7 (S7) up to S14. Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Recombinant human chorionic gonadotropin (r-hCG)

Intervention Type: DRUG

Recombinant human chorionic gonadotropin (r-hCG) will be administered as a single dose of 250 mcg subcutaneously, when follicular response is adequate (that is, less than or equal to \[=\<\] 3 follicles with a mean diameter of greater than or equal to \[\>=\] 14 millimeter \[mm\], and one or two of these follicles with a diameter of \>= 17 mm).

AS900672-Enriched 40 mcg

Group Type: EXPERIMENTAL

AS900672-Enriched 40 mcg

Intervention Type: DRUG

Single injection of AS900672-Enriched (hyperglycosylated r-hFSH), 40 mcg will be administered subcutaneously on S1. Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Follitropin alfa 75 international unit (IU)

Intervention Type: DRUG

Follitropin alfa (Gonal-f®) 75 IU will be administered subcutaneously once daily from S1 up to Stimulation Day 14 (S14) based upon ovarian response, until recombinant human chorionic gonadotropin (r-hCG) administration day. Subjects who will be receiving AS900672-Enriched 10, 20, 30 and 40 mcg will also receive daily dose of follitropin alfa 75 IU subcutaneously from Stimulation Day 7 (S7) up to S14. Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Recombinant human chorionic gonadotropin (r-hCG)

Intervention Type: DRUG

Recombinant human chorionic gonadotropin (r-hCG) will be administered as a single dose of 250 mcg subcutaneously, when follicular response is adequate (that is, less than or equal to \[=\<\] 3 follicles with a mean diameter of greater than or equal to \[\>=\] 14 millimeter \[mm\], and one or two of these follicles with a diameter of \>= 17 mm).

Follitropin alfa 75 IU

Group Type: ACTIVE_COMPARATOR

Follitropin alfa 75 international unit (IU)

Intervention Type: DRUG

Follitropin alfa (Gonal-f®) 75 IU will be administered subcutaneously once daily from S1 up to Stimulation Day 14 (S14) based upon ovarian response, until recombinant human chorionic gonadotropin (r-hCG) administration day. Subjects who will be receiving AS900672-Enriched 10, 20, 30 and 40 mcg will also receive daily dose of follitropin alfa 75 IU subcutaneously from Stimulation Day 7 (S7) up to S14. Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Recombinant human chorionic gonadotropin (r-hCG)

Intervention Type: DRUG

Recombinant human chorionic gonadotropin (r-hCG) will be administered as a single dose of 250 mcg subcutaneously, when follicular response is adequate (that is, less than or equal to \[=\<\] 3 follicles with a mean diameter of greater than or equal to \[\>=\] 14 millimeter \[mm\], and one or two of these follicles with a diameter of \>= 17 mm).

Interventions

AS900672-Enriched 10 microgram (mcg)

Single injection of AS900672-Enriched (hyperglycosylated recombinant human follicle stimulating hormone \[r-hFSH\]), 10 mcg will be administered subcutaneously on Stimulation Day 1 (S1). Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Intervention Type: DRUG

AS900672-Enriched 20 mcg

Single injection of AS900672-Enriched (hyperglycosylated r-hFSH), 20 mcg will be administered subcutaneously on S1. Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Intervention Type: DRUG

AS900672-Enriched 30 mcg

Single injection of AS900672-Enriched (hyperglycosylated r-hFSH), 30 mcg will be administered subcutaneously on S1. Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Intervention Type: DRUG

AS900672-Enriched 40 mcg

Single injection of AS900672-Enriched (hyperglycosylated r-hFSH), 40 mcg will be administered subcutaneously on S1. Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Intervention Type: DRUG

Follitropin alfa 75 international unit (IU)

Follitropin alfa (Gonal-f®) 75 IU will be administered subcutaneously once daily from S1 up to Stimulation Day 14 (S14) based upon ovarian response, until recombinant human chorionic gonadotropin (r-hCG) administration day. Subjects who will be receiving AS900672-Enriched 10, 20, 30 and 40 mcg will also receive daily dose of follitropin alfa 75 IU subcutaneously from Stimulation Day 7 (S7) up to S14. Duration of treatment cycle will be up to adequate follicular response received or maximum of 14 days.

Intervention Type: DRUG

Recombinant human chorionic gonadotropin (r-hCG)

Recombinant human chorionic gonadotropin (r-hCG) will be administered as a single dose of 250 mcg subcutaneously, when follicular response is adequate (that is, less than or equal to \[=\<\] 3 follicles with a mean diameter of greater than or equal to \[\>=\] 14 millimeter \[mm\], and one or two of these follicles with a diameter of \>= 17 mm).

Intervention Type: DRUG

Other Intervention Names

Hyperglycosylated r-hFSH; Hyperglycosylated r-hFSH; Hyperglycosylated r-hFSH; Hyperglycosylated r-hFSH; Gonal-f®; Follicle stimulating hormone (FSH)

Eligibility Criteria

Inclusion Criteria

• Oligo-anovulation defined by a menstrual period of 35 days to 6 months
• Spontaneous menses or a positive response to progestin within the prior 6 months or response to clomiphene citrate evidenced by ovulation within the prior 6 months
• Age between 18 and 36 years, inclusive, at time of informed consent signature
• Body mass index (BMI) 18 to 30 kilogram per square meter (kg/m^2), inclusive
• No clinically significant abnormalities in serum thyroid stimulating hormone (TSH), dehydroepiandrosterone (DHEA-S), prolactin, and FSH levels in the early follicular phase. Subjects low TSH level who receive replacement therapy could be enrolled at the discretion of the investigator if local laboratory results (thyroxine [T4]) demonstrated satisfactory thyroid function. Subjects receiving stable dose of dopamine agonists could be enrolled at the discretion of the investigator if local laboratory results demonstrated adequate control of prolactin levels
• No clinically significant abnormalities in fasting glucose and fasting insulin levels
• Normal uterine cavity and presence of at least one ovary with ipsilateral patent fallopian tube, as determined by means of hysterosalpingography, laparoscopy, hysteroscopy or combination of these procedures within the prior 3 years
• Papanicolaou (PAP) smear test without clinically significant abnormalities within 6 months prior to the first screening procedure. If PAP smear is not done, it must be performed as part of screening procedures
• Negative pregnancy test prior to randomization
• Male partner with semen analysis demonstrating adequacy for insemination via intercourse and/or intrauterine insemination (IUI) within 6 months prior to the first screening procedure. If semen analysis is not done, it must be performed as part of screening procedures
• Willing and able to comply with all protocol procedures, including pregnancy and neonatal follow-up
• Voluntary provision of written informed consent, prior to any trial-related procedure that is not part of normal medical care, with the understanding that the subject could withdraw consent at any time without prejudice to her future medical care, including willingness to provide follow-up information on babies born as part of this trial

Exclusion Criteria

• History of >=2 consecutive gonadotrophin stimulation cycles that did not lead to ovulation
• History of clomiphene citrate stimulation cycles of which none lead to ovulation
• Prior excessive response to gonadotrophin stimulation, defined as the development of at least 4 mature follicles (greater than [>]17 mm) or cancellation of the OI cycle due to excessive follicular response after treatment with FSH at a dose of less than 75 IU/day
• Previous severe ovarian hyperstimulation syndrome (OHSS)
• Administration of any gonadotrophin, clomiphene citrate, gonadotrophin releasing hormone (GnRH) analogue, tamoxifen or aromatase inhibitors within the prior 30 days
• Laparoscopic ovarian drilling and/or ovarian cauterization within the prior 6 months
• Any contraindication to pregnancy and/or to carrying pregnancy to term
• A clinical pregnancy that ended in a miscarriage within the prior 3 months
• History of >=3 consecutive miscarriages, due to any cause
• Abnormal gynecological bleeding of undetermined origin
• Clinically significant abnormal findings of the uterine cavity evident on a transvaginal pelvic ultrasound performed during screening
• Presence of endometriosis, Grade III - IV or requiring treatment
• Ovarian cyst with a mean diameter of >25 mm on the day of randomization
• History or suspicion of ovarian, uterine or mammary cancer
• Adrenal congenital hyperplasia, partial or complete enzymatic block
• Use of metformin or other insulin sensitizing agents related to infertility within the prior 2 months
• Known allergy or hypersensitivity to human gonadotrophin preparations or to compounds that are structurally similar to any of the other medications administered during the trial
• Any contra-indication to gonadotrophin therapy
• Known or suspected infection with human immunodeficiency virus (HIV), Hepatitis B or C in the trial subject or her male partner
• Any active substance abuse or history of drug, medication or alcohol abuse within 5 years
• Smoker consuming more than 5 cigarettes per day
• Serum testosterone (central laboratory) that is suggestive of ovarian tumor
• Previously randomized in this trial or participation in another investigational drug clinical trial within the prior 3 months
• Any medical condition, which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of r-hFSH
• Clinically significant concurrent disease (including diabetes mellitus and autoimmune diseases) that would compromise subject safety or interfere with the study assessments or clinically significant abnormal laboratory finding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 36 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Pellicer, Professor Dr

Role: PRINCIPAL_INVESTIGATOR

IVI Valencia

Locations

Merck Serono S.A.

Geneva, , Switzerland

Countries

Switzerland

Other Identifiers

27818

Identifier Type: -

Identifier Source: org_study_id