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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01735422
First received: November 23, 2012
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

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®).


Condition Intervention Phase
Infertility
Drug: r-hFSH
Drug: r-hLH
Drug: u-hCG
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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®).

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Ovulation rate [ Time Frame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days]) ] [ Designated as safety issue: No ]
  • 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]) ] [ Designated as safety issue: No ]
  • 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]) ] [ Designated as safety issue: No ]
  • 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]) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of participants with mono-follicular ovulation [ Time Frame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days]) ] [ Designated as safety issue: No ]
  • Number of participants with biochemical pregnancy [ Time Frame: Day 25-30 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days]) ] [ Designated as safety issue: No ]
  • 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]) ] [ Designated as safety issue: No ]
  • Serum androstenedione levels [ Time Frame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days]) ] [ Designated as safety issue: No ]
  • 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]) ] [ Designated as safety issue: No ]
  • 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]) ] [ Designated as safety issue: No ]
  • 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]) ] [ Designated as safety issue: No ]
  • Number of participants with clinical pregnancy [ Time Frame: Day 25-30 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days]) ] [ Designated as safety issue: No ]
  • 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]) ] [ Designated as safety issue: No ]

Enrollment: 67
Study Start Date: December 1999
Study Completion Date: July 2001
Primary Completion Date: July 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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).

  Eligibility

Ages Eligible for Study:   20 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01735422

Locations
Canada, Saskatchewan
Royal University Hospital
Saskatoon, Saskatchewan, Canada
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Medical Responsible Merck Serono International SA
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01735422     History of Changes
Other Study ID Numbers: 21321
Study First Received: November 23, 2012
Last Updated: February 3, 2014
Health Authority: Canada: Health Canada

Keywords provided by Merck KGaA:
Infertility
Ovulation induction
Recombinant human Luteinizing Hormone (r-hLH)
Urinary human Chorionic Gonadotrophin (u-hCG)
Recombinant human Follicle Stimulating Hormone (Gonal-f®)

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Chorionic Gonadotropin
Hormones
Follicle Stimulating Hormone
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 28, 2014