MedPath

LutrePulse Hypogonadotropic Hypogonadism

Registration Number
NCT01976728
Lead Sponsor
Ferring Pharmaceuticals
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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
39
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LutrePulse 10 µg/pulseGonadorelin acetate subcutaneous (SC) 10 μg/pulse as a fixed dose, administered via. OmniPod pumpGonadorelin acetate 10 µg/pulse
LutrePulse 15 µg/pulseGonadorelin acetate SC 15 μg/pulse as a fixed dose, administered via. OmniPod pumpGonadorelin acetate 15 µg/pulse
LutrePulse 20 µg/pulseGonadorelin acetate SC 20 μg/pulse as a fixed dose, administered via. OmniPod pumpGonadorelin acetate 20 µg/pulse
PlaceboPlacebo (SC 10, 15, or 20 μg/pulse as a fixed dose, administered via. OmniPod pump)Placebo
Primary Outcome Measures
NameTimeMethod
Ovulation RateFrom treatment Day 1 up to 4 weeks after second positive β-hCG test, approximately 9 weeks

Calculated as a proportion of subjects with at least 1 post-baseline progesterone level ≥ 6 ng/mL or subjects with confirmed positive serum β-human chorionic gonadotropin (β-hCG) (i.e., 2 positive results) or subjects with a gestational sac documented by transvaginal ultrasound (TVUS).

Secondary Outcome Measures
NameTimeMethod
Progesterone (P4) LevelsTreatment Days 19, 21, 23, 25, and 27

Proportion of participants with at least 1 post-baseline P4 level ≥ 10 ng/mL.

Clinical Pregnancy Rate2 to 4 weeks after a second positive serum β-hCG test

Proportion of subjects with presence of gestational sac and fetal heart movement on TVUS after a second positive serum β-hCG test.

Biochemical Pregnancy RateApproximately 14 days after LH surge

Proportion of subjects with a confirmed positive serum β-hCG test after luteinizing hormone (LH) surge.

LH Surge DetectionDaily from Day 11 until first positive LH surge or until Day 39

Proportion of subjects with a positive detection of LH surge, based on a Clearblue test which began when follicles with a mean diameter ≥14 mm were documented on TVUS.

Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mmFrom treatment Day 10 to treatment Day 21

Number of follicles with a mean diameter ≥14 mm collected from Days 10 or 11, until LH surge or Day 21.

Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mmFrom treatment Day 10 to treatment Day 21

Number of dominant follicles with a mean diameter ≥18 mm collected from Days 10 or 11, until LH surge or Day 21.

Luteal Phase Support: Maximum P4 LevelsTreatment Days 19, 21, 23, 25, and 27

Maximum of post-dose P4 levels collected on treatment Days 19 to 27 are presented.

Luteal Phase Support: Mean P4 LevelsMedian post-dose P4 values across Treatment Days 19, 21, 23, 25, and 27

Mean of post-dose P4 levels collected on treatment Days 19 to 27 are presented.

Change From Baseline in Follicle-stimulating Hormone (FSH)Baseline (pre-dose), Treatment Day 1, Treatment Day 10

FSH change from baseline in relation to the first dose (pulse) on Day 1 and Day 10

Change From Baseline in LHBaseline (pre-dose), Treatment Day 1, Treatment Day 10

LH change from baseline in relation to first dose (pulse) on Day 1 and Day 10

Mean Serum FSH and LH LevelsTreatment Days 1 and Day 10

Mean FSH and LH levels on Day 1 and Day 10.

Estradiol (E2) Serum LevelsAt treatment Day 1 and Day 10

E2 serum levels on Day 1 and Day 10.

Type, Intensity, and Frequency of Adverse Events (AEs)From treatment Day 1 to end-of-trial, approximately 10 weeks

An AE was defined as any untoward medical occurrence in a subject taking part in a clinical trial. Proportion of subjects with any AE (serious or non-serious) and intensity of AEs (classified as mild, moderate or severe) are presented.

Hematology, Clinical Chemistry, and UrinalysisFrom treatment Day 1 to end-of-trial, approximately 10 weeks

Proportion of subjects with markedly abnormal changes in hematology, clinical chemistry, and urinalysis.

Frequency and Severity of Ovarian Hyperstimulation Syndrome (OHSS)From treatment Day 1 to end-of-trial, approximately 10 weeks

Proportion of subjects reporting OHSS classified as mild, moderate, or severe.

Trial Locations

Locations (35)

Wayne State University Physicians Group

🇺🇸

Southfield, Michigan, United States

Fertility Treatment Center

🇺🇸

Tempe, Arizona, United States

Maine Medical Center-REI

🇺🇸

Portland, Maine, United States

Jones Institute for Reproductive Medicine

🇺🇸

Norfolk, Virginia, United States

Carolinas HealthCare System

🇺🇸

Charlotte, North Carolina, United States

Weill Cornell Medical College

🇺🇸

New York, New York, United States

Main Line Fertility Center

🇺🇸

Bryn Mawr, Pennsylvania, United States

Center for Assisted Reproduction

🇺🇸

Bedford, Texas, United States

Center of Reproductive Medicine

🇺🇸

Webster, Texas, United States

Cypress Medical Research Center

🇺🇸

Wichita, Kansas, United States

Fertility Centers of Illinois

🇺🇸

Chicago, Illinois, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Ohio Reproductive Medicine

🇺🇸

Columbus, Ohio, United States

University of Oklahoma Health Sciences Center, Abington IVF & Genetics, L.P.

🇺🇸

Oklahoma City, Oklahoma, United States

Houston Fertility Institute

🇺🇸

Houston, Texas, United States

Center for Reproductive Health UCSF

🇺🇸

San Francisco, California, United States

Women's Medical Research Group, LLC

🇺🇸

Clearwater, Florida, United States

UH Case Medical Center, MacDonald Clinical Trials

🇺🇸

Cleveland, Ohio, United States

Reproductive Associates of Delaware

🇺🇸

Newark, Delaware, United States

Ovo

🇨🇦

Montreal, Quebec, Canada

Georgia Reproductive Specialists

🇺🇸

Atlanta, Georgia, United States

University of Cincinnati Physicians

🇺🇸

Cincinnati, Ohio, United States

Fertility Associates of Memphis PLLC

🇺🇸

Memphis, Tennessee, United States

Columbia Fertility Associates

🇺🇸

Washington, District of Columbia, United States

Abington Reproductive Medicine, PC

🇺🇸

Abington, Pennsylvania, United States

Institute for Reproductive Health

🇺🇸

Cincinnati, Ohio, United States

Utah Fertility Center

🇺🇸

Pleasant Grove, Utah, United States

University of Pittsburgh, Magee-Womens Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

Penn State MS Hershey Medical Center, Penn State College of Medicine

🇺🇸

Hershey, Pennsylvania, United States

Olive Fertility Centre

🇨🇦

Vancouver, British Columbia, Canada

Center for Reproductive Medicine

🇺🇸

Orlando, Florida, United States

Lyndhurst Clinical Research

🇺🇸

Winston-Salem, North Carolina, United States

University of Colorado School of Medicine

🇺🇸

Aurora, Colorado, United States

Bluegrass Clinical Research Inc.

🇺🇸

Louisville, Kentucky, United States

Wake Forest University Health Sciences

🇺🇸

Winston-Salem, North Carolina, United States

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