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Trial · Interventional

TerminatedPhase 2Results postedRegistry data

AS900672-Enriched in Ovulation Induction

Overview

Status
Terminated
Phase
Phase 2
Enrollment
71 participants (actual)
Sponsor
Merck KGaA, Darmstadt, Germany · Industry
Design
Randomized · Single masking
Countries
1 country

Switzerland

Start
Dec 2007
Primary completion
Mar 2009
Completion
Mar 2009
First posted
5 Nov 2007 (estimated)
Last update posted
13 Feb 2014 (estimated)
Conditions
Ovulation Induction

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2007200820092010
  1. Ph 2

    AS900672-Enriched in Ovulation Induction

    NCT00553514

    Dec 2007 to Mar 2009

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

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

Arms5

  • Experimental

    AS900672-Enriched 10 mcg

  • Experimental

    AS900672-Enriched 20 mcg

  • Experimental

    AS900672-Enriched 30 mcg

  • Experimental

    AS900672-Enriched 40 mcg

  • Active comparator

    Follitropin alfa 75 IU

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Percentage of Participants With Ovulation

    Time frame · 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])

    Registry description

    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 outcomes(5)
  1. Percentage of Participants With Clinical Pregnancy

    Time frame · Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 14 days])

    Registry description

    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.

  2. Duration of Ovarian Stimulation

    Time frame · Stimulation Day 1 (S1) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])

    Registry description

    Ovarian stimulation included from first dose of study drug on S1 until day on which r-hCG was administered (r-hCG day).

  3. Duration of Supplemental Follitropin Alfa Treatment

    Time frame · Stimulation Day 7 (S7) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])

  4. Cumulative Dose of Supplemental Follitropin Alfa Administered

    Time frame · Stimulation Day 7 (S7) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])

  5. Number of Follicles With Mean Diameter Less Than (<) 11 Millimeter (mm) and Greater Than or Equal to (>=) 11 mm

    Time frame · Stimulation Day 5 (S5), S7 and r-hCG administration day (end of stimulation cycle [approximately 14 days])

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· 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])

Percentage of Participants With Ovulation

GroupValue (Percentage of participants)
AS900672-Enriched 10 Mcg46.2
AS900672-Enriched 20 Mcg46.2
AS900672-Enriched 30 Mcg38.5
AS900672-Enriched 40 Mcg33.3
Follitropin Alfa 75 IU53.8
Secondary and other outcome results(5)
Secondary outcomeNumber· Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 14 days])

Percentage of Participants With Clinical Pregnancy

GroupValue (Percentage of participants)
AS900672-Enriched 10 Mcg23.1
AS900672-Enriched 20 Mcg0.0
AS900672-Enriched 30 Mcg7.7
AS900672-Enriched 40 Mcg16.7
Follitropin Alfa 75 IU0.0
Secondary outcomeMean· Stimulation Day 1 (S1) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])

Duration of Ovarian Stimulation

GroupValue (Days)Spread
AS900672-Enriched 10 Mcg10.05.3
AS900672-Enriched 20 Mcg11.83.4
AS900672-Enriched 30 Mcg14.01.4
AS900672-Enriched 40 Mcg10.83.7
Follitropin Alfa 75 IU10.63.2
Secondary outcomeMean· Stimulation Day 7 (S7) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])

Duration of Supplemental Follitropin Alfa Treatment

GroupValue (Days)Spread
AS900672-Enriched 10 Mcg6.61.4
AS900672-Enriched 20 Mcg6.61.4
AS900672-Enriched 30 Mcg7.71.5
AS900672-Enriched 40 Mcg5.62.2
Follitropin Alfa 75 IU5.52.7
Secondary outcomeMean· Stimulation Day 7 (S7) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])

Cumulative Dose of Supplemental Follitropin Alfa Administered

GroupValue (IU)Spread
AS900672-Enriched 10 Mcg476.3122.5
AS900672-Enriched 20 Mcg493.8108.3
AS900672-Enriched 30 Mcg556.7134.2
AS900672-Enriched 40 Mcg398.9167.9
Follitropin Alfa 75 IU397.5226.5
Secondary outcomeMean· Stimulation Day 5 (S5), S7 and 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

GroupValue (Follicles)Spread
AS900672-Enriched 10 Mcg23.613.8
AS900672-Enriched 20 Mcg28.729.4
AS900672-Enriched 30 Mcg23.26.7
AS900672-Enriched 40 Mcg20.916.7
Follitropin Alfa 75 IU21.313.7

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
AS900672-Enriched 10 McgSingle injection of AS900672-Enriched (hyperglycosylated recombinant human follicle stimulating hormone \[r-hFSH\]), 10 microgram (mcg) administered subcutaneously on Stimulation day 1 (S1) followed by a daily dose of follitropin alfa 75 international unit (IU) subcutaneously starting from Stimulation Day 7 (S7) up to Stimulation Day 14 (S14) based upon ovarian response, until recombinant human chorionic gonadotropin (r-hCG) administration day. When follicular response was 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), ovulation was triggered by single 250 mcg subcutaneous r-hCG injection. Duration of treatment cycle was up to adequate follicular response received or maximum of 14 days.–0 / 147 / 14
AS900672-Enriched 20 McgSingle injection of AS900672-Enriched (hyperglycosylated r-hFSH), 20 mcg administered subcutaneously on S1 followed by a daily dose of follitropin alfa 75 IU subcutaneously starting from S7 up to S14 based upon ovarian response, until r-hCG administration day. When follicular response was adequate (that is, =\< 3 follicles with a mean diameter of \>=14 mm, and one or two of these follicles with a diameter of \>=17 mm), ovulation was triggered by single 250 mcg subcutaneous r-hCG injection. Duration of treatment cycle was up to adequate follicular response received or maximum of 14 days.–0 / 143 / 14
AS900672-Enriched 30 McgSingle injection of AS900672-Enriched (hyperglycosylated r-hFSH), 30 mcg administered subcutaneously on S1 followed by a daily dose of follitropin alfa 75 IU subcutaneously starting from S7 up to S14 based upon ovarian response, until r-hCG administration day. When follicular response was adequate (that is, =\< 3 follicles with a mean diameter of \>=14 mm, and one or two of these follicles with a diameter of \>=17 mm), ovulation was triggered by single 250 mcg subcutaneous r-hCG injection. Duration of treatment cycle was up to adequate follicular response received or maximum of 14 days.–0 / 156 / 15
AS900672-Enriched 40 McgSingle injection of AS900672-Enriched (hyperglycosylated r-hFSH), 40 mcg administered subcutaneously on S1 followed by a daily dose of follitropin alfa 75 IU subcutaneously starting from S7 up to S14 based upon ovarian response, until r-hCG administration day. When follicular response was adequate (that is, =\< 3 follicles with a mean diameter of \>=14 mm, and one or two of these follicles with a diameter of \>=17 mm), ovulation was triggered by single 250 mcg subcutaneous r-hCG injection. Duration of treatment cycle was up to adequate follicular response received or maximum of 14 days.–0 / 134 / 13
Follitropin Alfa 75 IUFollitropin alfa (Gonal-f®) 75 IU administered subcutaneously once daily from S1 up to S14 based upon ovarian response, until r-hCG administration day. When follicular response was adequate (that is, =\< 3 follicles with a mean diameter of \>=14 mm, and one or two of these follicles with a diameter of \>=17 mm), ovulation was triggered by single 250 mcg subcutaneous r-hCG injection. Duration of treatment cycle was up to adequate follicular response received or maximum of 14 days.–0 / 157 / 15

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
Female
Age
from 18 Years up to 36 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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