Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L])

This study has been terminated.
(Please see "Purpose" statement)
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00328926
First received: May 20, 2006
Last updated: August 4, 2013
Last verified: August 2013
  Purpose

Sponsor has decided to discontinue Luveris® in the United States (US) due to level of customer demand for this product, and not due to any efficacy or safety concerns.


Condition Intervention Phase
Hypogonadotropic Hypogonadism
Drug: Luveris® 75 IU
Drug: Luveris® 25 IU
Drug: Placebo
Drug: Recombinant human follicle stimulating hormone (r-hFSH)
Drug: Recombinant human chorionic gonadotropin (r-hCG)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IV, Multicenter, Randomized, Double-blinded, Clinical Trial to Confirm the Efficacy of the 75 IU Dose of Luveris® vs. Placebo When Administered With Follitropin Alfa for Induction of Follicular Development and Pregnancy in Hypogonadotropic Hypogonadal Women With Profound LH Deficiency, as Defined by a Baseline LH Level <1.2 IU/L

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Time to Clinical Pregnancy [ Time Frame: Stimulation Day 1 up to clinical pregnancy (Day 35-42 post r-hCG administration day [end of stimulation cycle {approximately 21 days}]) ] [ Designated as safety issue: No ]
    Clinical pregnancy was defined as the presence of one or more fetal sac with fetal heart activity on the Day 35-42 post r-hCG ultrasound examination.


Secondary Outcome Measures:
  • Percentage of Participants With Cumulative Clinical Pregnancy [ Time Frame: Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 21 days]) ] [ Designated as safety issue: No ]
    Clinical pregnancy was defined as the presence of one or more fetal sac with fetal heart activity on the Day 35-42 post r-hCG ultrasound examination. Cumulative clinical pregnancy referred to all clinical pregnancy that occurred during all the 3 treatment cycles.

  • Percentage of Participants With Cumulative Ovulation [ Time Frame: Recombinant human chorionic gonadotropin (r-hCG) administration day (end of stimulation cycle [approximately 21 days]) ] [ Designated as safety issue: No ]
    Ovulation was defined as a mid-luteal phase progesterone (P4) level greater than or equal to (>=) 10 nanogram per milliliter (ng/mL). Cumulative ovulation referred to all ovulations that occurred during all the 3 treatment cycles.


Enrollment: 11
Study Start Date: March 2006
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Luveris® 75 IU Drug: Luveris® 75 IU
Recombinant human luteinizing hormone (r-hLH, lutropin alfa, Luveris®), 75 IU will be administered subcutaneously once daily. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and estradiol [E2] levels). Total duration will be of 3 treatment cycles.
Other Names:
  • Lutropin alfa
  • Recombinant human luteinizing hormone (r-hLH)
Drug: Recombinant human follicle stimulating hormone (r-hFSH)
Fixed dose of recombinant human follicle stimulating hormone (r-hFSH, follitropin alfa) 75 to 150 IU will be administered subcutaneously for 7 days. After 7 days of treatment, if the subject response will suboptimal, based on follicular growth and serum E2 levels, follitropin alfa dose adjusted to maximal dose of 225 IU. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles.
Other Name: Follitropin alfa
Drug: Recombinant human chorionic gonadotropin (r-hCG)
When the follicular response will adequate, ovulation will be triggered by a single 250 microgram subcutaneous injection of recombinant human chorionic gonadotropin (r-hCG, choriogonadotropin alfa). Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles.
Other Name: Choriogonadotropin alfa
Active Comparator: Luveris® 25 IU Drug: Luveris® 25 IU
Recombinant human luteinizing hormone (r-hLH, lutropin alfa, Luveris®), 25 IU will be administered subcutaneously once daily. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles.
Other Names:
  • Lutropin alfa
  • Recombinant human luteinizing hormone (r-hLH)
Drug: Recombinant human follicle stimulating hormone (r-hFSH)
Fixed dose of recombinant human follicle stimulating hormone (r-hFSH, follitropin alfa) 75 to 150 IU will be administered subcutaneously for 7 days. After 7 days of treatment, if the subject response will suboptimal, based on follicular growth and serum E2 levels, follitropin alfa dose adjusted to maximal dose of 225 IU. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles.
Other Name: Follitropin alfa
Drug: Recombinant human chorionic gonadotropin (r-hCG)
When the follicular response will adequate, ovulation will be triggered by a single 250 microgram subcutaneous injection of recombinant human chorionic gonadotropin (r-hCG, choriogonadotropin alfa). Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles.
Other Name: Choriogonadotropin alfa
Placebo Comparator: Placebo Drug: Placebo
Placebo will be administered subcutaneously once daily. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles.
Drug: Recombinant human follicle stimulating hormone (r-hFSH)
Fixed dose of recombinant human follicle stimulating hormone (r-hFSH, follitropin alfa) 75 to 150 IU will be administered subcutaneously for 7 days. After 7 days of treatment, if the subject response will suboptimal, based on follicular growth and serum E2 levels, follitropin alfa dose adjusted to maximal dose of 225 IU. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles.
Other Name: Follitropin alfa
Drug: Recombinant human chorionic gonadotropin (r-hCG)
When the follicular response will adequate, ovulation will be triggered by a single 250 microgram subcutaneous injection of recombinant human chorionic gonadotropin (r-hCG, choriogonadotropin alfa). Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles.
Other Name: Choriogonadotropin alfa

Detailed Description:

To confirm the efficacy of the 75 IU dose of Luveris® compared to placebo when administered concomitantly with follitropin alfa for induction of clinical pregnancy in women with hypogonadotropic hypogonadism and profound LH deficiency (LH <1.2 IU/L), and to study the efficacy of a lower dose (25 IU) of Luveris® compared to placebo when administered concomitantly with follitropin alfa for induction of follicular development in women with hypogonadotropic hypogonadism and profound LH deficiency (LH <1.2 IU/L).

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be premenopausal, between 18 and 40 years of age inclusive on the day of consent
  • Have a clinical history of hypogonadotropic hypogonadism (World health organization [WHO] Group I type of anovulation) on the basis of congenital or acquired hypothalamic or pituitary endocrine dysfunction in the presence of qualifying screening laboratories
  • Have no prior treatment cycles with gonadotropins or gonadotropin releasing hormone (GnRH) (gonadotropin naïve)
  • Have discontinued estrogen-progesterone replacement therapy at least one month before the screening procedure
  • Have primary or secondary amenorrhea
  • Have a negative progestin challenge test performed during Screening
  • Have the following hormonal values in a centrally analyzed fasting blood sample, drawn within 6 weeks before initiation of treatment:

    • Follicle-Stimulating Hormone (FSH): less than (<)5 international unit per liter (IU/L)
    • Leutinizing hormone (LH): <1.2 IU/L (a second Baseline serum LH level will be repeated two weeks after the initial LH draw)
    • Prolactin: < 43.3 nanogram per milliliter (ng/mL) (<1040 milli-international unit per liter [mIU/L])
    • Thyroid Stimulating Hormone (TSH): <6.5 micro-international units per milliliter (mcIU/mL)
    • Free Thyroxin (T4): 0.8-1.8 nanogram per deciliter (ng/dL) (11-24 picomole per liter [pmol/L])
    • Testosterone: <1.0 ng/mL (<3.5 nanomole per liter [nmol/L])
  • Have an endovaginal pelvic ultrasound scan showing (i) no clinically significant uterine abnormality, (ii) no ovarian tumor or cyst, and (iii) less than or equal to (=<)13 small follicles (mean diameter =<10 milliliter [mm]) on the largest section through each ovary
  • Have a normal cervical pap smear within 6 months of the initial visit
  • Where indicated, have a normal or unchanged computed tomography (CT) scan or nuclear magnetic resonance (NMR) scan of the hypothalamic pituitary region on file
  • Have a body mass index (BMI) between 18.4 and 31.4 kilogram per square meter (kg/m^2)
  • 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 subject at any time without prejudice to her future medical care

Exclusion Criteria:

  • Any medical condition which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug
  • Any pre-existing medical condition which would compromise the subject's ability to conceive in vivo or to successfully complete a pregnancy
  • Ongoing pregnancy
  • Clinically important systemic disease (example: insulin-dependent diabetes mellitus, epilepsy, serious migraine, intermittent purpura, hepatic, renal or cardiovascular disease, serious corticoid-dependent asthma)
  • Known infection with human immunodeficiency virus (HIV), Hepatitis B or C
  • Ovarian enlargement or cyst of unknown etiology
  • Abnormal gynecological bleeding of undetermined origin
  • Previous or current hormone dependent tumor
  • Known active substance abuse or eating disorder
  • Known central nervous system (CNS) Lesions: In cases where hypogonadotropic hypogonadism (HH) is secondary to a CNS lesion or its treatment
  • Exercise program exceeding 10 hours per week
  • Is planning to undergo in vitro fertilization, intracytoplasmic sperm injection or another assisted reproductive technology (ART) procedure, other than intrauterine insemination, in the course of a study treatment cycle
  • Currently undergoing treatment with psychotropic medication or with any other medication known to interfere with normal reproductive function (example: neuroleptics, dopamine antagonists)
  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: NCT00328926

Locations
United States, Massachusetts
U.S. Medical Information, 1-888-275-7376
Rockland, Massachusetts, United States, 02370
Sponsors and Collaborators
EMD Serono
Investigators
Study Director: Medical Responsible Merck Serono S.A., Geneva
  More Information

Additional Information:
No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00328926     History of Changes
Other Study ID Numbers: 26109
Study First Received: May 20, 2006
Results First Received: May 22, 2013
Last Updated: August 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by EMD Serono:
Hypogonadotropic Hypogonadism (LH <1.2 IU/L)
Placebo
Luveris® 75 IU
Luveris® 25 IU
Recombinant human chorionic gonadotropin (r-hCG)

Additional relevant MeSH terms:
Hypogonadism
Gonadal Disorders
Endocrine System Diseases
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 29, 2014