A Study to Evaluate Safety and Efficacy of Recombinant Human Luteinizing Hormone (r-hLH) Compared With Urinary Human Chorionic Gonadotrophin (u-hCG) to Trigger Ovulation in Infertile Women

February 3, 2014 updated by: Merck KGaA, Darmstadt, Germany

A Phase II, Single Center, Open, Randomized, Parallel Group, Dose Finding Study to Assess the Safety and Efficacy of Recombinant Human Luteinizing Hormone (r-hLH), Compared With Urinary Human Chorionic Gonadotrophin (u-hCG), in Inducing Ovulation in Infertile Women Undergoing Stimulation of Follicular Development With Recombinant Human Follicle Stimulating Hormone (Gonal F®).

This is a single center, open-label, randomized, parallel group, dose finding study to evaluate safety and efficacy of recombinant human luteinizing hormone (r-hLH, LHadi®), compared with urinary human chorionic gonadotrophin (u-hCG, Profasi®), both given subcutaneously, in inducing ovulation in infertile women undergoing stimulation of follicular growth with recombinant human follicle stimulating hormone (r-hFSH, Gonal-F®).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
67

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada
        • Royal University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 40 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Infertile woman wishing to conceive and justifying ovarian stimulation treatment with gonadotrophins for in vivo conception
  • Aged 20-40 years (inclusive)
  • Male partner with acceptable semen analysis for intra-uterine insemination, according to center's standard practice

  • Have the following hormone serum levels measured locally during early (Day 2-4) follicular phase (if menstruating) or at anytime (if not menstruating):

    • Follicle stimulating hormone (FSH) less than 12 international unit per liter (IU/L)
    • Prolactin (PRL) less than 800 milli international unit per liter (mIU/l)
    • Lutenizing hormone (LH), P4, Testosterone (T) and Dehydroepiandrosterone sulphate (DHEA-S) for documentation purposes
  • At least one patent tube, as assessed with hysterosalpingography (HSG), ultrasound (U/S) or laparoscopy performed within 3 years prior to beginning r-hFSH treatment
  • Uterine cavity without abnormalities which, in the Investigator's opinion, could impair embryo implantation or pregnancy evolution as assessed with HSG, hysteroscopy (HSC) or U/S performed within 3 years prior to beginning r-hFSH treatment
  • Body mass index (BMI) greater than or equal to 18 and less than or equal to 35 kilogram per square meter (kg/m^2)
  • Negative serum or urinary pregnancy test prior to beginning r-hFSH treatment
  • Be willing and able to comply with the protocol for the duration of the study
  • Have given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care

Exclusion Criteria:

  • Any contraindication to being pregnant and/or carrying a pregnancy to term
  • Clinically significant systemic disease (screening for Human Immunodeficiency Virus (HIV) and Hepatitis B and C surface antigens had to be performed to confirm eligibility, unless data obtained within one year prior to beginning r-hFSH treatment was available)
  • Any medical condition which in the judgment of the Investigator's and sponsor may have interfered with the absorption, distribution, metabolism or excretion of the study drug
  • Persistent ovarian cyst with a mean diameter larger than 20 mm or ovarian endometrioma, as assessed with U/S performed prior to beginning r-hFSH treatment
  • Severe endometriosis (American Fertility Society Classification Stage III or IV)
  • World health organization (WHO) Group I anovulation
  • Pelvic inflammatory disease within 1 year prior to beginning r-hFSH treatment
  • Treatment with clomiphene citrate or gonadotrophins within 1 month prior to beginning r-hFSH treatment
  • Abnormal undiagnosed gynecological bleeding
  • Known allergy or hypersensitivity to human gonadotrophins preparations
  • Known or current substance abuse
  • Previous participation in this study or simultaneous participation in another clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: r-hLH (825 International Units [IU])
Drug: r-hFSH
Daily r-hFSH treatment will be administered subcutaneously at a starting dose according to the site's standard practice from Day 3-5 of menstrual cycle up to follicular development or 28 days. Dose can be altered according to ovarian response (reduced to 75 IU/day; increased to 225 IU/day).
Other Names:
  • Gonal-f®
Drug: r-hLH
Ovulation triggering will be performed using a single injection of r-hLH injection subcutaneously at a dose of 825 or 2750 or 5500 or 11,000 or 22,000 IU as soon as follicles satisfy the criteria for follicular development, that is at least 1 follicle with diameter >= 18 mm, not more than 5 follicles with diameter >= 15 mm and with E2 levels less than 9000 picomoles per liter (pmol/L).
Other Names:
  • LHadi®
EXPERIMENTAL: r-hLH (2750 IU)
Drug: r-hFSH
Daily r-hFSH treatment will be administered subcutaneously at a starting dose according to the site's standard practice from Day 3-5 of menstrual cycle up to follicular development or 28 days. Dose can be altered according to ovarian response (reduced to 75 IU/day; increased to 225 IU/day).
Other Names:
  • Gonal-f®
Drug: r-hLH
Ovulation triggering will be performed using a single injection of r-hLH injection subcutaneously at a dose of 825 or 2750 or 5500 or 11,000 or 22,000 IU as soon as follicles satisfy the criteria for follicular development, that is at least 1 follicle with diameter >= 18 mm, not more than 5 follicles with diameter >= 15 mm and with E2 levels less than 9000 picomoles per liter (pmol/L).
Other Names:
  • LHadi®
EXPERIMENTAL: r-hLH (5500 IU)
Drug: r-hFSH
Daily r-hFSH treatment will be administered subcutaneously at a starting dose according to the site's standard practice from Day 3-5 of menstrual cycle up to follicular development or 28 days. Dose can be altered according to ovarian response (reduced to 75 IU/day; increased to 225 IU/day).
Other Names:
  • Gonal-f®
Drug: r-hLH
Ovulation triggering will be performed using a single injection of r-hLH injection subcutaneously at a dose of 825 or 2750 or 5500 or 11,000 or 22,000 IU as soon as follicles satisfy the criteria for follicular development, that is at least 1 follicle with diameter >= 18 mm, not more than 5 follicles with diameter >= 15 mm and with E2 levels less than 9000 picomoles per liter (pmol/L).
Other Names:
  • LHadi®
EXPERIMENTAL: r-hLH (11000 IU)
Drug: r-hFSH
Daily r-hFSH treatment will be administered subcutaneously at a starting dose according to the site's standard practice from Day 3-5 of menstrual cycle up to follicular development or 28 days. Dose can be altered according to ovarian response (reduced to 75 IU/day; increased to 225 IU/day).
Other Names:
  • Gonal-f®
Drug: r-hLH
Ovulation triggering will be performed using a single injection of r-hLH injection subcutaneously at a dose of 825 or 2750 or 5500 or 11,000 or 22,000 IU as soon as follicles satisfy the criteria for follicular development, that is at least 1 follicle with diameter >= 18 mm, not more than 5 follicles with diameter >= 15 mm and with E2 levels less than 9000 picomoles per liter (pmol/L).
Other Names:
  • LHadi®
EXPERIMENTAL: r-hLH (22000 IU)
Drug: r-hFSH
Daily r-hFSH treatment will be administered subcutaneously at a starting dose according to the site's standard practice from Day 3-5 of menstrual cycle up to follicular development or 28 days. Dose can be altered according to ovarian response (reduced to 75 IU/day; increased to 225 IU/day).
Other Names:
  • Gonal-f®
Drug: r-hLH
Ovulation triggering will be performed using a single injection of r-hLH injection subcutaneously at a dose of 825 or 2750 or 5500 or 11,000 or 22,000 IU as soon as follicles satisfy the criteria for follicular development, that is at least 1 follicle with diameter >= 18 mm, not more than 5 follicles with diameter >= 15 mm and with E2 levels less than 9000 picomoles per liter (pmol/L).
Other Names:
  • LHadi®
ACTIVE_COMPARATOR: u-hCG (5000 IU)
Drug: r-hFSH
Daily r-hFSH treatment will be administered subcutaneously at a starting dose according to the site's standard practice from Day 3-5 of menstrual cycle up to follicular development or 28 days. Dose can be altered according to ovarian response (reduced to 75 IU/day; increased to 225 IU/day).
Other Names:
  • Gonal-f®
Drug: u-hCG
Ovulation triggering will be performed using a single injection of 5000 IU of u-hCG as soon as follicles satisfy the criteria for follicular development, that is at least 1 follicle with diameter >= 18 mm, not more than 5 follicles with diameter >= 15 mm and with E2 levels less than 9000 picomoles per liter (pmol/L).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Ovulation rate
Time Frame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Ratio of ruptured follicles per follicle with diameter greater than or equal to (>=) 15 millimeter (mm)
Time Frame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Number of follicles with diameter greater than or equal to (>=) 11 millimeter (mm)
Time Frame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Ratio of ruptured follicles per follicle with diameter greater than or equal to (>=) 11 millimeter (mm)
Time Frame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Percentage of participants with mono-follicular ovulation
Time Frame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Number of participants with biochemical pregnancy
Time Frame: Day 25-30 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 25-30 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Serum estradiol (E2) levels
Time Frame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Serum androstenedione levels
Time Frame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Serum total renin levels
Time Frame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Serum vascular endothelial growth factor (VEGF) levels
Time Frame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Endometrial thickness
Time Frame: Day 0, 1, 2, 3, 4 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 0, 1, 2, 3, 4 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Number of participants with clinical pregnancy
Time Frame: Day 25-30 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 25-30 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Serum progesterone (P4) levels
Time Frame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck KGaA, Darmstadt, Germany

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Responsible, Merck Serono International SA

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 1999

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2001

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2001

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 23, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 27, 2012

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 28, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 4, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 3, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 21321

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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