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

Merck KGaA (EMD Serono)

Status and phase: Terminated; Phase 4

Conditions: Hypogonadotropic Hypogonadism

Treatments: Drug: Luveris® 75 IU; Drug: Recombinant human chorionic gonadotropin (r-hCG); Drug: Luveris® 25 IU; Drug: Recombinant human follicle stimulating hormone (r-hFSH); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00328926

26109

Details and patient eligibility

About

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.

Full 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).

Enrollment: 11 patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: No 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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11 participants in 3 patient groups, including a placebo group

Luveris® 75 IU

Active Comparator group

Treatment:

Drug: Recombinant human follicle stimulating hormone (r-hFSH)

Drug: Recombinant human chorionic gonadotropin (r-hCG)

Drug: Luveris® 75 IU

Luveris® 25 IU

Active Comparator group

Treatment:

Drug: Recombinant human follicle stimulating hormone (r-hFSH)

Drug: Recombinant human chorionic gonadotropin (r-hCG)

Drug: Luveris® 25 IU

Placebo

Placebo Comparator group

Treatment:

Drug: Recombinant human follicle stimulating hormone (r-hFSH)

Drug: Recombinant human chorionic gonadotropin (r-hCG)

Drug: Placebo