Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L])
Condition: Hypogonadotropic Hypogonadism
MeSH terms: Hypogonadism
Intervention: Luveris® 75 IU; Luveris® 25 IU; Placebo; Recombinant human follicle stimulating hormone (r-hFSH); Recombinant human chorionic gonadotropin (r-hCG)
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.; 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.; 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.; 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.; 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.
Intervention MeSH terms: Chorionic Gonadotropin; Hormones; Follicle Stimulating Hormone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 11.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: No
Keywords: Hypogonadotropic Hypogonadism (LH <1.2 IU/L); Placebo; Luveris® 75 IU; Luveris® 25 IU; Recombinant human chorionic gonadotropin (r-hCG)

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.
    

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)