Clinical trial NCT00328926: 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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hypogonadotropic Hypogonadism
Keywords: Hypogonadotropic Hypogonadism (LH <1.2 IU/L)
Placebo
Luveris® 75 IU
Luveris® 25 IU
Recombinant human chorionic gonadotropin (r-hCG)
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
First posted: 2006-05-24
Enrollment: 11
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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)

Primary outcomes:
measure: Time to Clinical Pregnancy
timeFrame: Stimulation Day 1 up to clinical pregnancy (Day 35-42 post r-hCG administration day [end of stimulation cycle {approximately 21 days}])
Secondary outcomes:
measure: Percentage of Participants With Cumulative Clinical Pregnancy
timeFrame: Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 21 days])
measure: Percentage of Participants With Cumulative Ovulation
timeFrame: Recombinant human chorionic gonadotropin (r-hCG) administration day (end of stimulation cycle [approximately 21 days])
Other outcomes:
Locations:
city: Rockland
country: United States
facility: U.S. Medical Information, 1-888-275-7376
state: Massachusetts
Study officials:
affiliation: Merck Serono S.A., Geneva
name: Medical Responsible
role: STUDY_DIRECTOR
References: