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

Primary Purpose

Hypogonadotropic Hypogonadism

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Luveris® 75 IU
Luveris® 25 IU
Placebo
Recombinant human follicle stimulating hormone (r-hFSH)
Recombinant human chorionic gonadotropin (r-hCG)
Sponsored by
EMD Serono
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypogonadotropic Hypogonadism focused on measuring Hypogonadotropic Hypogonadism (LH <1.2 IU/L), Placebo, Luveris® 75 IU, Luveris® 25 IU, Recombinant human chorionic gonadotropin (r-hCG)

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

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)

Sites / Locations

  • U.S. Medical Information, 1-888-275-7376

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Luveris® 75 IU

Luveris® 25 IU

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Time to Clinical Pregnancy
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
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
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.

Full Information

First Posted
May 20, 2006
Last Updated
August 4, 2013
Sponsor
EMD Serono
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1. Study Identification

Unique Protocol Identification Number
NCT00328926
Brief Title
Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L])
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2013
Overall Recruitment Status
Terminated
Why Stopped
Please see "Purpose" statement
Study Start Date
March 2006 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
May 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EMD Serono

4. Oversight

5. Study Description

Brief Summary
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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogonadotropic Hypogonadism
Keywords
Hypogonadotropic Hypogonadism (LH <1.2 IU/L), Placebo, Luveris® 75 IU, Luveris® 25 IU, Recombinant human chorionic gonadotropin (r-hCG)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Luveris® 75 IU
Arm Type
Active Comparator
Arm Title
Luveris® 25 IU
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Luveris® 75 IU
Other Intervention Name(s)
Lutropin alfa, Recombinant human luteinizing hormone (r-hLH)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Luveris® 25 IU
Other Intervention Name(s)
Lutropin alfa, Recombinant human luteinizing hormone (r-hLH)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Recombinant human follicle stimulating hormone (r-hFSH)
Other Intervention Name(s)
Follitropin alfa
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Recombinant human chorionic gonadotropin (r-hCG)
Other Intervention Name(s)
Choriogonadotropin alfa
Intervention Description
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.
Primary Outcome Measure Information:
Title
Time to Clinical Pregnancy
Description
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.
Time Frame
Stimulation Day 1 up to clinical pregnancy (Day 35-42 post r-hCG administration day [end of stimulation cycle {approximately 21 days}])
Secondary Outcome Measure Information:
Title
Percentage of Participants With Cumulative Clinical Pregnancy
Description
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.
Time Frame
Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 21 days])
Title
Percentage of Participants With Cumulative Ovulation
Description
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.
Time Frame
Recombinant human chorionic gonadotropin (r-hCG) administration day (end of stimulation cycle [approximately 21 days])

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck Serono S.A., Geneva
Official's Role
Study Director
Facility Information:
Facility Name
U.S. Medical Information, 1-888-275-7376
City
Rockland
State/Province
Massachusetts
ZIP/Postal Code
02370
Country
United States

12. IPD Sharing Statement

Links:
URL
http://fertilitylifelines.com
Description
Full FDA approved prescribing information can be found here

Learn more about this trial

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

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