LutrePulse Hypogonadotropic Hypogonadism
Primary Purpose
Primary Amenorrhea With Hypogonadotropic Hypogonadism
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Gonadorelin acetate subcutaneous (SC) 10 μg/pulse as a fixed dose, administered via. OmniPod pump
Gonadorelin acetate SC 15 μg/pulse as a fixed dose, administered via. OmniPod pump
Gonadorelin acetate SC 20 μg/pulse as a fixed dose, administered via. OmniPod pump
Placebo (SC 10, 15, or 20 μg/pulse as a fixed dose, administered via. OmniPod pump)
Sponsored by
About this trial
This is an interventional treatment trial for Primary Amenorrhea With Hypogonadotropic Hypogonadism
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
Sites / Locations
- Fertility Treatment Center
- Center for Reproductive Health UCSF
- University of Colorado School of Medicine
- Reproductive Associates of Delaware
- Columbia Fertility Associates
- Women's Medical Research Group, LLC
- Center for Reproductive Medicine
- Georgia Reproductive Specialists
- Fertility Centers of Illinois
- Cypress Medical Research Center
- Bluegrass Clinical Research Inc.
- Maine Medical Center-REI
- Massachusetts General Hospital
- Wayne State University Physicians Group
- Weill Cornell Medical College
- Carolinas HealthCare System
- Lyndhurst Clinical Research
- Wake Forest University Health Sciences
- Institute for Reproductive Health
- University of Cincinnati Physicians
- UH Case Medical Center, MacDonald Clinical Trials
- Ohio Reproductive Medicine
- University of Oklahoma Health Sciences Center, Abington IVF & Genetics, L.P.
- Abington Reproductive Medicine, PC
- Main Line Fertility Center
- Penn State MS Hershey Medical Center, Penn State College of Medicine
- University of Pittsburgh, Magee-Womens Hospital
- Fertility Associates of Memphis PLLC
- Center for Assisted Reproduction
- Houston Fertility Institute
- Center of Reproductive Medicine
- Utah Fertility Center
- Jones Institute for Reproductive Medicine
- Olive Fertility Centre
- Ovo
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
LutrePulse 10 µg/pulse
LutrePulse 15 µg/pulse
LutrePulse 20 µg/pulse
Placebo
Arm Description
Gonadorelin acetate 10 µg/pulse
Gonadorelin acetate 15 µg/pulse
Gonadorelin acetate 20 µg/pulse
Placebo
Outcomes
Primary Outcome Measures
Ovulation Rate
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
Progesterone (P4) Levels
Proportion of participants with at least 1 post-baseline P4 level ≥ 10 ng/mL.
Clinical Pregnancy Rate
Proportion of subjects with presence of gestational sac and fetal heart movement on TVUS after a second positive serum β-hCG test.
Biochemical Pregnancy Rate
Proportion of subjects with a confirmed positive serum β-hCG test after luteinizing hormone (LH) surge.
LH Surge Detection
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 mm
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 mm
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 Levels
Maximum of post-dose P4 levels collected on treatment Days 19 to 27 are presented.
Luteal Phase Support: Mean P4 Levels
Mean of post-dose P4 levels collected on treatment Days 19 to 27 are presented.
Change From Baseline in Follicle-stimulating Hormone (FSH)
FSH change from baseline in relation to the first dose (pulse) on Day 1 and Day 10
Change From Baseline in LH
LH change from baseline in relation to first dose (pulse) on Day 1 and Day 10
Mean Serum FSH and LH Levels
Mean FSH and LH levels on Day 1 and Day 10.
Estradiol (E2) Serum Levels
E2 serum levels on Day 1 and Day 10.
Type, Intensity, and Frequency of Adverse Events (AEs)
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 Urinalysis
Proportion of subjects with markedly abnormal changes in hematology, clinical chemistry, and urinalysis.
Frequency and Severity of Ovarian Hyperstimulation Syndrome (OHSS)
Proportion of subjects reporting OHSS classified as mild, moderate, or severe.
Full Information
NCT ID
NCT01976728
First Posted
October 15, 2013
Last Updated
February 9, 2021
Sponsor
Ferring Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01976728
Brief Title
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
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
April 1, 2014 (Actual)
Primary Completion Date
February 23, 2018 (Actual)
Study Completion Date
February 23, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ferring Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Amenorrhea With Hypogonadotropic Hypogonadism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
39 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LutrePulse 10 µg/pulse
Arm Type
Experimental
Arm Description
Gonadorelin acetate 10 µg/pulse
Arm Title
LutrePulse 15 µg/pulse
Arm Type
Experimental
Arm Description
Gonadorelin acetate 15 µg/pulse
Arm Title
LutrePulse 20 µg/pulse
Arm Type
Experimental
Arm Description
Gonadorelin acetate 20 µg/pulse
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Gonadorelin acetate subcutaneous (SC) 10 μg/pulse as a fixed dose, administered via. OmniPod pump
Other Intervention Name(s)
LutrePulse
Intervention Type
Drug
Intervention Name(s)
Gonadorelin acetate SC 15 μg/pulse as a fixed dose, administered via. OmniPod pump
Other Intervention Name(s)
LutrePulse
Intervention Type
Drug
Intervention Name(s)
Gonadorelin acetate SC 20 μg/pulse as a fixed dose, administered via. OmniPod pump
Other Intervention Name(s)
LutrePulse
Intervention Type
Drug
Intervention Name(s)
Placebo (SC 10, 15, or 20 μg/pulse as a fixed dose, administered via. OmniPod pump)
Primary Outcome Measure Information:
Title
Ovulation Rate
Description
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).
Time Frame
From treatment Day 1 up to 4 weeks after second positive β-hCG test, approximately 9 weeks
Secondary Outcome Measure Information:
Title
Progesterone (P4) Levels
Description
Proportion of participants with at least 1 post-baseline P4 level ≥ 10 ng/mL.
Time Frame
Treatment Days 19, 21, 23, 25, and 27
Title
Clinical Pregnancy Rate
Description
Proportion of subjects with presence of gestational sac and fetal heart movement on TVUS after a second positive serum β-hCG test.
Time Frame
2 to 4 weeks after a second positive serum β-hCG test
Title
Biochemical Pregnancy Rate
Description
Proportion of subjects with a confirmed positive serum β-hCG test after luteinizing hormone (LH) surge.
Time Frame
Approximately 14 days after LH surge
Title
LH Surge Detection
Description
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.
Time Frame
Daily from Day 11 until first positive LH surge or until Day 39
Title
Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm
Description
Number of follicles with a mean diameter ≥14 mm collected from Days 10 or 11, until LH surge or Day 21.
Time Frame
From treatment Day 10 to treatment Day 21
Title
Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm
Description
Number of dominant follicles with a mean diameter ≥18 mm collected from Days 10 or 11, until LH surge or Day 21.
Time Frame
From treatment Day 10 to treatment Day 21
Title
Luteal Phase Support: Maximum P4 Levels
Description
Maximum of post-dose P4 levels collected on treatment Days 19 to 27 are presented.
Time Frame
Treatment Days 19, 21, 23, 25, and 27
Title
Luteal Phase Support: Mean P4 Levels
Description
Mean of post-dose P4 levels collected on treatment Days 19 to 27 are presented.
Time Frame
Median post-dose P4 values across Treatment Days 19, 21, 23, 25, and 27
Title
Change From Baseline in Follicle-stimulating Hormone (FSH)
Description
FSH change from baseline in relation to the first dose (pulse) on Day 1 and Day 10
Time Frame
Baseline (pre-dose), Treatment Day 1, Treatment Day 10
Title
Change From Baseline in LH
Description
LH change from baseline in relation to first dose (pulse) on Day 1 and Day 10
Time Frame
Baseline (pre-dose), Treatment Day 1, Treatment Day 10
Title
Mean Serum FSH and LH Levels
Description
Mean FSH and LH levels on Day 1 and Day 10.
Time Frame
Treatment Days 1 and Day 10
Title
Estradiol (E2) Serum Levels
Description
E2 serum levels on Day 1 and Day 10.
Time Frame
At treatment Day 1 and Day 10
Title
Type, Intensity, and Frequency of Adverse Events (AEs)
Description
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.
Time Frame
From treatment Day 1 to end-of-trial, approximately 10 weeks
Title
Hematology, Clinical Chemistry, and Urinalysis
Description
Proportion of subjects with markedly abnormal changes in hematology, clinical chemistry, and urinalysis.
Time Frame
From treatment Day 1 to end-of-trial, approximately 10 weeks
Title
Frequency and Severity of Ovarian Hyperstimulation Syndrome (OHSS)
Description
Proportion of subjects reporting OHSS classified as mild, moderate, or severe.
Time Frame
From treatment Day 1 to end-of-trial, approximately 10 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Compliance
Organizational Affiliation
Ferring Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Fertility Treatment Center
City
Tempe
State/Province
Arizona
Country
United States
Facility Name
Center for Reproductive Health UCSF
City
San Francisco
State/Province
California
Country
United States
Facility Name
University of Colorado School of Medicine
City
Aurora
State/Province
Colorado
Country
United States
Facility Name
Reproductive Associates of Delaware
City
Newark
State/Province
Delaware
Country
United States
Facility Name
Columbia Fertility Associates
City
Washington
State/Province
District of Columbia
Country
United States
Facility Name
Women's Medical Research Group, LLC
City
Clearwater
State/Province
Florida
Country
United States
Facility Name
Center for Reproductive Medicine
City
Orlando
State/Province
Florida
Country
United States
Facility Name
Georgia Reproductive Specialists
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Fertility Centers of Illinois
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Cypress Medical Research Center
City
Wichita
State/Province
Kansas
Country
United States
Facility Name
Bluegrass Clinical Research Inc.
City
Louisville
State/Province
Kentucky
Country
United States
Facility Name
Maine Medical Center-REI
City
Portland
State/Province
Maine
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Wayne State University Physicians Group
City
Southfield
State/Province
Michigan
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
Country
United States
Facility Name
Carolinas HealthCare System
City
Charlotte
State/Province
North Carolina
Country
United States
Facility Name
Lyndhurst Clinical Research
City
Winston-Salem
State/Province
North Carolina
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
Country
United States
Facility Name
Institute for Reproductive Health
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
University of Cincinnati Physicians
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
UH Case Medical Center, MacDonald Clinical Trials
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
Ohio Reproductive Medicine
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
University of Oklahoma Health Sciences Center, Abington IVF & Genetics, L.P.
City
Oklahoma City
State/Province
Oklahoma
Country
United States
Facility Name
Abington Reproductive Medicine, PC
City
Abington
State/Province
Pennsylvania
Country
United States
Facility Name
Main Line Fertility Center
City
Bryn Mawr
State/Province
Pennsylvania
Country
United States
Facility Name
Penn State MS Hershey Medical Center, Penn State College of Medicine
City
Hershey
State/Province
Pennsylvania
Country
United States
Facility Name
University of Pittsburgh, Magee-Womens Hospital
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
Facility Name
Fertility Associates of Memphis PLLC
City
Memphis
State/Province
Tennessee
Country
United States
Facility Name
Center for Assisted Reproduction
City
Bedford
State/Province
Texas
Country
United States
Facility Name
Houston Fertility Institute
City
Houston
State/Province
Texas
Country
United States
Facility Name
Center of Reproductive Medicine
City
Webster
State/Province
Texas
Country
United States
Facility Name
Utah Fertility Center
City
Pleasant Grove
State/Province
Utah
Country
United States
Facility Name
Jones Institute for Reproductive Medicine
City
Norfolk
State/Province
Virginia
Country
United States
Facility Name
Olive Fertility Centre
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
Ovo
City
Montreal
State/Province
Quebec
Country
Canada
12. IPD Sharing Statement
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LutrePulse Hypogonadotropic Hypogonadism
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