AS900672-Enriched in Ovulation Induction

Phase 2

Terminated

Conditions: Ovulation Induction

Interventions: Drug: AS900672-Enriched 10 microgram (mcg)
Drug: AS900672-Enriched 20 mcg
Drug: AS900672-Enriched 30 mcg
Drug: AS900672-Enriched 40 mcg
Drug: Follitropin alfa 75 international unit (IU)
Drug: Recombinant human chorionic gonadotropin (r-hCG)

Registration Number: NCT00553514

Lead Sponsor: Merck KGaA, Darmstadt, Germany

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 71

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AS900672-Enriched 10 mcg	AS900672-Enriched 10 microgram (mcg)	-
AS900672-Enriched 10 mcg	Recombinant human chorionic gonadotropin (r-hCG)	-
AS900672-Enriched 20 mcg	AS900672-Enriched 20 mcg	-
AS900672-Enriched 20 mcg	Recombinant human chorionic gonadotropin (r-hCG)	-
AS900672-Enriched 30 mcg	AS900672-Enriched 30 mcg	-
AS900672-Enriched 30 mcg	Recombinant human chorionic gonadotropin (r-hCG)	-
AS900672-Enriched 40 mcg	AS900672-Enriched 40 mcg	-
AS900672-Enriched 40 mcg	Recombinant human chorionic gonadotropin (r-hCG)	-
Follitropin alfa 75 IU	Follitropin alfa 75 international unit (IU)	-
Follitropin alfa 75 IU	Recombinant human chorionic gonadotropin (r-hCG)	-
AS900672-Enriched 10 mcg	Follitropin alfa 75 international unit (IU)	-
AS900672-Enriched 20 mcg	Follitropin alfa 75 international unit (IU)	-
AS900672-Enriched 30 mcg	Follitropin alfa 75 international unit (IU)	-
AS900672-Enriched 40 mcg	Follitropin alfa 75 international unit (IU)	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Ovulation	Mid-luteal phase progesterone assessed 5-10 days or clinical pregnancy 35-42 days after recombinant human chorionic gonadotropin (r-hCG) administration day (end of stimulation cycle [approximately 14 days])	Ovulation was defined as a mid-luteal phase progesterone (P4) level \>= 30 nanomole per liter (nmol/L) (10 nanogram per milliliter \[ng/mL\]). In the absence of a positive progesterone response, clinical pregnancy was also considered as evidence of ovulation.

Secondary Outcome Measures

Name	Time	Method
Duration of Supplemental Follitropin Alfa Treatment	Stimulation Day 7 (S7) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])
Cumulative Dose of Supplemental Follitropin Alfa Administered	Stimulation Day 7 (S7) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])
Number of Follicles With Mean Diameter Less Than (<) 11 Millimeter (mm) and Greater Than or Equal to (>=) 11 mm	Stimulation Day 5 (S5), S7 and r-hCG administration day (end of stimulation cycle [approximately 14 days])
Percentage of Participants With Clinical Pregnancy	Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 14 days])	Clinical pregnancy was defined as the presence of one or more fetal sacs with fetal heart activity on the Day 35-42 post r-hCG ultrasound examination.
Duration of Ovarian Stimulation	Stimulation Day 1 (S1) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])	Ovarian stimulation included from first dose of study drug on S1 until day on which r-hCG was administered (r-hCG day).