Clinical trial NCT01976728: LutrePulse Hypogonadotropic Hypogonadism
Official title: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Evaluating Three Doses of Subcutaneous Pulsatile GnRH Administered Via OmniPod Pump for Ovulation Induction in Female Subjects With Primary Amenorrhea With Hypogonadotropic Hypogonadism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Amenorrhea With Hypogonadotropic Hypogonadism
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-11-06
Enrollment: 39
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: To compare the ovulation rate in women with primary amenorrhea with hypogonadotropic hypogonadism following pulsatile gonadotropin-releasing hormone (GnRH) treatment using the OmniPod pump versus placebo


Eligibility criteria: Inclusion Criteria:

* Women 18-40 years old
* Body mass index (BMI) between 18 and 38 kg/m2
* Clinical history or recently diagnosed with primary amenorrhea with hypogonadotropic hypogonadism
* Hormonal values in a centrally analyzed fasting blood sample: FSH \<5 IU/L and mean LH \<5 IU/L
* Desire to become pregnant
* Discontinued estrogen-progesterone replacement therapy at least 1 month before screening
* Negative progestin challenge test performed during screening
* PAP smear within 24 months of the initial visit
* Normal or stable CT scan or MRI scan of the hypothalamic pituitary region
* Prolactin and thyroid-stimulating hormone (TSH) within normal clinical laboratory limits
* Male partner with normal semen analysis, including volume, liquefaction time, sperm count, and motility, according to the local laboratory normal criteria, within the past year
* Normal transvaginal ultrasound at screening with respect to uterus and adnexa (presence of both ovaries and tubes, without evidence of clinically significant abnormality) and with normal uterine cavity and normal cervix
* Tube patency on saline tubal perfusion, hysterosalpingography or laparoscopy on file within the past 2 years

Exclusion Criteria:

* Any medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the drug
* A history of, or currently diagnosed with clinically important cardiovascular, pulmonary (e.g. serious corticosteroid-dependent asthma), gastrointestinal, hepatic, metabolic, renal, endocrinological (e.g. insulin dependent diabetes mellitus), or neurological (e.g. epilepsy, serious migraine, central nervous system (CNS) lesions (in cases where hypogonadotropic hypogonadism is secondary to a CNS lesion or its treatment) abnormality
* A history of adrenal or uncontrolled thyroid disorders, or hyperprolactinemia
* Prior treatment cycle with gonadotropins or GnRH within the last 2 months
* Known allergy to study drug or its components
* Infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C
* Ovarian enlargement or cyst of unknown etiology
* Abnormal gynecological bleeding of undetermined origin
* Previous or current hormone-dependent tumor
* Known active substance abuse
* Planning to undergo in vitro fertilization procedure in the course of a study treatment cycle
* Currently undergoing treatment with gonadotropin hormones (FSH and LH), psychotropic medication, sex hormones, or any other medication known to interfere with normal reproductive function or that can affect GnRH secretion (e.g. neuroleptics, dopamine antagonists, spironolactone, levodopa, phenothiazine, digoxin)
* Ongoing pregnancy or lactation

Primary outcomes:
measure: Ovulation Rate
timeFrame: From treatment Day 1 up to 4 weeks after second positive β-hCG test, approximately 9 weeks
Secondary outcomes:
measure: Progesterone (P4) Levels
timeFrame: Treatment Days 19, 21, 23, 25, and 27
measure: Clinical Pregnancy Rate
timeFrame: 2 to 4 weeks after a second positive serum β-hCG test
measure: Biochemical Pregnancy Rate
timeFrame: Approximately 14 days after LH surge
measure: LH Surge Detection
timeFrame: Daily from Day 11 until first positive LH surge or until Day 39
measure: Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm
timeFrame: From treatment Day 10 to treatment Day 21
measure: Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm
timeFrame: From treatment Day 10 to treatment Day 21
measure: Luteal Phase Support: Maximum P4 Levels
timeFrame: Treatment Days 19, 21, 23, 25, and 27
measure: Luteal Phase Support: Mean P4 Levels
timeFrame: Median post-dose P4 values across Treatment Days 19, 21, 23, 25, and 27
measure: Change From Baseline in Follicle-stimulating Hormone (FSH)
timeFrame: Baseline (pre-dose), Treatment Day 1, Treatment Day 10
measure: Change From Baseline in LH
timeFrame: Baseline (pre-dose), Treatment Day 1, Treatment Day 10
measure: Mean Serum FSH and LH Levels
timeFrame: Treatment Days 1 and Day 10
measure: Estradiol (E2) Serum Levels
timeFrame: At treatment Day 1 and Day 10
measure: Type, Intensity, and Frequency of Adverse Events (AEs)
timeFrame: From treatment Day 1 to end-of-trial, approximately 10 weeks
measure: Hematology, Clinical Chemistry, and Urinalysis
timeFrame: From treatment Day 1 to end-of-trial, approximately 10 weeks
measure: Frequency and Severity of Ovarian Hyperstimulation Syndrome (OHSS)
timeFrame: From treatment Day 1 to end-of-trial, approximately 10 weeks
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Fertility Treatment Center
state: Arizona
city: San Francisco
country: United States
facility: Center for Reproductive Health UCSF
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: Newark
country: United States
facility: Reproductive Associates of Delaware
state: Delaware
city: Washington
country: United States
facility: Columbia Fertility Associates
state: District of Columbia
city: Clearwater
country: United States
facility: Women's Medical Research Group, LLC
state: Florida
city: Orlando
country: United States
facility: Center for Reproductive Medicine
state: Florida
city: Atlanta
country: United States
facility: Georgia Reproductive Specialists
state: Georgia
city: Chicago
country: United States
facility: Fertility Centers of Illinois
state: Illinois
city: Wichita
country: United States
facility: Cypress Medical Research Center
state: Kansas
city: Louisville
country: United States
facility: Bluegrass Clinical Research Inc.
state: Kentucky
city: Portland
country: United States
facility: Maine Medical Center-REI
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Southfield
country: United States
facility: Wayne State University Physicians Group
state: Michigan
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Charlotte
country: United States
facility: Carolinas HealthCare System
state: North Carolina
city: Winston-Salem
country: United States
facility: Lyndhurst Clinical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: Institute for Reproductive Health
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Physicians
state: Ohio
city: Cleveland
country: United States
facility: UH Case Medical Center, MacDonald Clinical Trials
state: Ohio
city: Columbus
country: United States
facility: Ohio Reproductive Medicine
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center, Abington IVF & Genetics, L.P.
state: Oklahoma
city: Abington
country: United States
facility: Abington Reproductive Medicine, PC
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Main Line Fertility Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State MS Hershey Medical Center, Penn State College of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Magee-Womens Hospital
state: Pennsylvania
city: Memphis
country: United States
facility: Fertility Associates of Memphis PLLC
state: Tennessee
city: Bedford
country: United States
facility: Center for Assisted Reproduction
state: Texas
city: Houston
country: United States
facility: Houston Fertility Institute
state: Texas
city: Webster
country: United States
facility: Center of Reproductive Medicine
state: Texas
city: Pleasant Grove
country: United States
facility: Utah Fertility Center
state: Utah
city: Norfolk
country: United States
facility: Jones Institute for Reproductive Medicine
state: Virginia
city: Vancouver
country: Canada
facility: Olive Fertility Centre
state: British Columbia
city: Montreal
country: Canada
facility: Ovo
state: Quebec
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References: