LutrePulse Hypogonadotropic Hypogonadism

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Primary Amenorrhea With Hypogonadotropic Hypogonadism

Intervention / Treatment
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* Drug: Gonadorelin acetate subcutaneous (SC) 10 μg/pulse as a fixed dose, administered via. OmniPod pump
* Drug: Gonadorelin acetate SC 15 μg/pulse as a fixed dose, administered via. OmniPod pump
* Drug: Gonadorelin acetate SC 20 μg/pulse as a fixed dose, administered via. OmniPod pump
* Drug: Placebo (SC 10, 15, or 20 μg/pulse as a fixed dose, administered via. OmniPod pump)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LutrePulse 10 µg/pulse<br>Gonadorelin acetate 10 µg/pulse | Drug: Gonadorelin acetate subcutaneous (SC) 10 μg/pulse as a fixed dose, administered via. OmniPod pump<br> <br> * Other names: LutrePulse;|
| Experimental: LutrePulse 15 µg/pulse<br>Gonadorelin acetate 15 µg/pulse | Drug: Gonadorelin acetate SC 15 μg/pulse as a fixed dose, administered via. OmniPod pump<br> <br> * Other names: LutrePulse;|
| Experimental: LutrePulse 20 µg/pulse<br>Gonadorelin acetate 20 µg/pulse | Drug: Gonadorelin acetate SC 20 μg/pulse as a fixed dose, administered via. OmniPod pump<br> <br> * Other names: LutrePulse;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo (SC 10, 15, or 20 μg/pulse as a fixed dose, administered via. OmniPod pump)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | From treatment Day 1 up to 4 weeks after second positive β-hCG test, approximately 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progesterone (P4) Levels | Proportion of participants with at least 1 post-baseline P4 level ≥ 10 ng/mL. | Treatment Days 19, 21, 23, 25, and 27 | 
| 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. | 2 to 4 weeks 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. | Approximately 14 days after 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. | Daily from Day 11 until first positive LH surge or until Day 39 | 
| 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. | From treatment Day 10 to treatment 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. | From treatment Day 10 to treatment Day 21 | 
| Luteal Phase Support: Maximum P4 Levels | Maximum of post-dose P4 levels collected on treatment Days 19 to 27 are presented. | Treatment Days 19, 21, 23, 25, and 27 | 
| Luteal Phase Support: Mean P4 Levels | Mean of post-dose P4 levels collected on treatment Days 19 to 27 are presented. | Median post-dose P4 values across Treatment Days 19, 21, 23, 25, and 27 | 
| 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 | Baseline (pre-dose), Treatment Day 1, Treatment Day 10 | 
| Change From Baseline in LH | LH change from baseline in relation to first dose (pulse) on Day 1 and Day 10 | Baseline (pre-dose), Treatment Day 1, Treatment Day 10 | 
| Mean Serum FSH and LH Levels | Mean FSH and LH levels on Day 1 and Day 10. | Treatment Days 1 and Day 10 | 
| Estradiol (E2) Serum Levels | E2 serum levels on Day 1 and Day 10. | At treatment 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. | From treatment Day 1 to end-of-trial, approximately 10 weeks | 
| Hematology, Clinical Chemistry, and Urinalysis | Proportion of subjects with markedly abnormal changes in hematology, clinical chemistry, and urinalysis. | From treatment Day 1 to end-of-trial, approximately 10 weeks | 
| Frequency and Severity of Ovarian Hyperstimulation Syndrome (OHSS) | Proportion of subjects reporting OHSS classified as mild, moderate, or severe. | From treatment Day 1 to end-of-trial, approximately 10 weeks |