A Randomised, Phase II, Comparative Study With a Parallel Control for Evaluating the Efficacy and Safety of Combined Treatment of Lutropin Alpha and Recombinant Human Luteinizing Hormone in the Middle of the Controlled Ovarian Stimulation Follicular Phase in Women With Reduced Ovarian Reserve

NCT ID: NCT01110707

Last Updated: 2018-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-10
• Study Completion Date: 2006-11-15

Brief Summary

This was a prospective, randomized, Phase II, comparative study with a parallel control for evaluating the efficacy and safety of combined treatment of recombinant human follicle stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH). The combined treatment was administered at the middle of the follicular phase in subjects undergoing in-vitro fertilisation (IVF) through intracytoplasmic sperm injection (ICSI) and transfer of embryos (ET).

Conditions

Infertility; Ovulation Induction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

r-hFSH + r-hLH

Group Type: EXPERIMENTAL

Recombinant human follicle stimulating hormone (r-hFSH)

Intervention Type: DRUG

Subjects will receive subcutaneous injection of recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).

Recombinant human luteinizing hormone (r-hLH)

Intervention Type: DRUG

Subjects will receive subcutaneous injection of recombinant human luteinizing hormone (r-hLH) 150 IU/day until the end of ovarian stimulation.

r-hFSH alone

Group Type: ACTIVE_COMPARATOR

Recombinant human luteinizing hormone (r-hLH)

Intervention Type: DRUG

Subjects will receive subcutaneous injection of recombinant human luteinizing hormone (r-hLH) 150 IU/day until the end of ovarian stimulation.

Interventions

Recombinant human follicle stimulating hormone (r-hFSH)

Subjects will receive subcutaneous injection of recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).

Intervention Type: DRUG

Recombinant human luteinizing hormone (r-hLH)

Subjects will receive subcutaneous injection of recombinant human luteinizing hormone (r-hLH) 150 IU/day until the end of ovarian stimulation.

Intervention Type: DRUG

Other Intervention Names

GONAL-f; Follitrophin alpha; Luveris; Lutrophin alpha

Eligibility Criteria

Inclusion Criteria

• Postmenopausal woman aged between 35 and 40 years that wishes to become pregnant
• Subjects with basal serum level (beginning of the follicular phase, Day 2-5) of Follicle-Stimulating Hormone (FSH) less than 10 IU/L determined within the 6 months prior as well as Luteinizing hormone (LH) and Estradiol (E2) levels within the normal interval according to standard data for the area where the study was carried out
• Subjects with a regular menstrual cycles between 25-35 days
• Subjects with infertility that justifies treatment with IVF/ET or ICSI
• Subjects undergoing controlled ovarian stimulation (COS) with r-hFSH using a long protocol with GnRH-a
• Sperm availability from the subject's current partner unless it is planned to use sperm from a donor
• Subjects with both ovaries
• Subjects with uterine cavity capable of withstanding the implantation of the embryo and pregnancy
• Subjects whose vaginal smear (PAP) was normal within the 3 years prior to starting the stimulation
• Subjects with body mass index (BMI) between 18 and 30 at the time of participation in the study
• Subjects in whom at least 30 days have elapsed since the last dose of clomiphene citrate or gonadotropins before beginning treatment with GnRH-a
• Subjects with a negative pregnancy test result using the beta human chorionic gonadotropin (beta-hCG) test (in urine or blood) before beginning treatment with GnRH-a
• Subjects willing to and capable of following the protocol during the entire study
• Subjects who have provided informed written consent before carrying out any procedure related with the study (that is not part of the normal medical treatment followed by the subject)

Exclusion Criteria

• Subject who were human immunodeficiency virus, hepatitis B and C virus positive
• Subjects suffering from any clinically important systematic disease, hypothalmic or pituitary tumour, ovarian, uterine or breast cancer, endocrinopathy and/or medical alterations, biochemical or hematological that as per the investigators judgement, may interfere with the gonadotropin treatment
• Subjects who have been subjected to more than 2 assisted reproductive cycles in the past
• Subjects who have cancelled 2 cycles in the past
• Subjects who have cryopreserved embryos from previous assisted reproductive cycles
• Subjects with non explained vaginal haemorrhages
• Subjects with polycystic ovary, enlarged ovary or ovarian cysts of unknown aetiology
• Subjects with any contraindication for getting pregnant or taking the pregnancy to full term
• Subjects with known allergy to the gonadotropin preparations or any of its excipients
• Subjects with current drug use or prior personal history of alcohol, drug or psychiatric drug dependency in the past five years
• Subjects with prior participation in this study or simultaneous participation in a different clinical study with a medication under investigation
• Subjects who were not willing to or incapable of following the study protocol

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

Hospital de Cruces, Plaza de Cruces, 12, 48903

Vizcaya, , Spain

Countries

Spain

References

Matorras R, Prieto B, Exposito A, Mendoza R, Crisol L, Herranz P, Burgues S. Mid-follicular LH supplementation in women aged 35-39 years undergoing ICSI cycles: a randomized controlled study. Reprod Biomed Online. 2009 Dec;19(6):879-87. doi: 10.1016/j.rbmo.2009.09.016.

Reference Type: RESULT

PMID: 20031032 (View on PubMed)

Matorras R, Prieto B, Exposito A, Mendoza R, Crisol L, Herranz P, Burgues S. Mid-follicular LH supplementation in women aged 35-39 years undergoing ICSI cycles: a randomized controlled study. Reprod Biomed Online. 2011 Feb;22 Suppl 1:S43-51. doi: 10.1016/S1472-6483(11)60008-4.

Reference Type: RESULT

PMID: 21575849 (View on PubMed)

Other Identifiers

IMP 25186

Identifier Type: -

Identifier Source: org_study_id