Primary Amenorrhea With Hypogonadotropic Hypogonadism
Conditions
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
Interventions
DRUGGonadorelin acetate subcutaneous (SC) 10 μg/pulse as a fixed dose, administered via. OmniPod pump
DRUGGonadorelin acetate SC 15 μg/pulse as a fixed dose, administered via. OmniPod pump
DRUGGonadorelin acetate SC 20 μg/pulse as a fixed dose, administered via. OmniPod pump
DRUGPlacebo (SC 10, 15, or 20 μg/pulse as a fixed dose, administered via. OmniPod pump)
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ovulation Rate | From 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
| Measure | Time frame | Description |
|---|---|---|
| Clinical Pregnancy Rate | 2 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 Rate | Approximately 14 days after LH surge | Proportion of subjects with a confirmed positive serum β-hCG test after luteinizing hormone (LH) surge. |
| LH Surge Detection | Daily 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 mm | From 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 mm | From 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 Levels | Treatment 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 Levels | Median 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. |
| Progesterone (P4) Levels | Treatment Days 19, 21, 23, 25, and 27 | Proportion of participants with at least 1 post-baseline P4 level ≥ 10 ng/mL. |
| Change From Baseline in LH | Baseline (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 Levels | Treatment Days 1 and Day 10 | Mean FSH and LH levels on Day 1 and Day 10. |
| Estradiol (E2) Serum Levels | At 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 Urinalysis | From 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. |
| 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 |
Countries
Canada, United States
Participant flow
Recruitment details
A total of 24 sites randomized subjects to the trial between April 2014 and February 2018. The trial sites that randomized subjects to the trial were: 22 in the United States of America and 2 in Canada.
Pre-assignment details
A total of 54 subjects were screened, of which 39 subjects were randomized. Of the 39 randomized subjects, 10 were randomized to LutrePulse 10 μg/pulse, 9 were randomized to LutrePulse 15 μg/pulse, 10 were randomized to LutrePulse 20 μg/pulse and 10 were randomized to placebo.
Participants by arm
| Arm | Count |
|---|---|
| LutrePulse 10 µg/Pulse Gonadorelin acetate SC 10 μg/pulse as a fixed dose, administered via. OmniPod pump | 10 |
| LutrePulse 15 µg/Pulse Gonadorelin acetate SC 15 μg/pulse as a fixed dose, administered via. OmniPod pump | 9 |
| LutrePulse 20 µg/Pulse Gonadorelin acetate SC 20 μg/pulse as a fixed dose, administered via. OmniPod pump | 10 |
| Placebo Placebo (SC 10, 15, or 20 μg/pulse as a fixed dose, administered via. OmniPod pump) | 10 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Subject missed multiple doses of IMP | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | LutrePulse 10 µg/Pulse | LutrePulse 15 µg/Pulse | LutrePulse 20 µg/Pulse | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 30.9 years STANDARD_DEVIATION 4.2 | 29.6 years STANDARD_DEVIATION 6.02 | 30.9 years STANDARD_DEVIATION 5.67 | 29.5 years STANDARD_DEVIATION 2.55 | 30.2 years STANDARD_DEVIATION 4.63 |
| BMI | 29.41 kg/m^2 STANDARD_DEVIATION 6.065 | 23.70 kg/m^2 STANDARD_DEVIATION 4.567 | 26.53 kg/m^2 STANDARD_DEVIATION 4.218 | 23.85 kg/m^2 STANDARD_DEVIATION 3.953 | 25.93 kg/m^2 STANDARD_DEVIATION 5.159 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 7 Participants | 9 Participants | 7 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 7 Participants | 7 Participants | 8 Participants | 31 Participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 10 Participants | 10 Participants | 39 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 8 | 0 / 10 | 0 / 11 |
| other Total, other adverse events | 5 / 10 | 3 / 8 | 4 / 10 | 4 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 | 0 / 10 | 0 / 11 |
Outcome results
Primary
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).
Time frame: From treatment Day 1 up to 4 weeks after second positive β-hCG test, approximately 9 weeks
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LutrePulse 10 µg/Pulse | Ovulation Rate | 1 Participants |
| LutrePulse 15 µg/Pulse | Ovulation Rate | 4 Participants |
| LutrePulse 20 µg/Pulse | Ovulation Rate | 5 Participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Ovulation Rate | 9 Participants |
| Placebo | Ovulation Rate | 0 Participants |
Comparison: The primary efficacy analysis compared the pooled ovulation rate of the LutrePulse 15 μg and 20 μg group to placebo.p-value: 0.012Fisher Exact
Secondary
Biochemical Pregnancy Rate
Proportion of subjects with a confirmed positive serum β-hCG test after luteinizing hormone (LH) surge.
Time frame: Approximately 14 days after LH surge
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LutrePulse 10 µg/Pulse | Biochemical Pregnancy Rate | 0 Participants |
| LutrePulse 15 µg/Pulse | Biochemical Pregnancy Rate | 3 Participants |
| LutrePulse 20 µg/Pulse | Biochemical Pregnancy Rate | 5 Participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Biochemical Pregnancy Rate | 8 Participants |
| Placebo | Biochemical Pregnancy Rate | 0 Participants |
Comparison: Biochemical pregnancy rates of the pooled LutrePulse 15 μg and 20 μg group were compared to placebo.p-value: 0.0246Fisher Exact
Secondary
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
Time frame: Baseline (pre-dose), Treatment Day 1, Treatment Day 10
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LutrePulse 10 µg/Pulse | Change From Baseline in Follicle-stimulating Hormone (FSH) | FSH (Day 1) | 1.30 IU/L |
| LutrePulse 10 µg/Pulse | Change From Baseline in Follicle-stimulating Hormone (FSH) | FSH (Day 10) | 0.04 IU/L |
| LutrePulse 15 µg/Pulse | Change From Baseline in Follicle-stimulating Hormone (FSH) | FSH (Day 10) | -0.04 IU/L |
| LutrePulse 15 µg/Pulse | Change From Baseline in Follicle-stimulating Hormone (FSH) | FSH (Day 1) | 5.40 IU/L |
| LutrePulse 20 µg/Pulse | Change From Baseline in Follicle-stimulating Hormone (FSH) | FSH (Day 1) | 2.70 IU/L |
| LutrePulse 20 µg/Pulse | Change From Baseline in Follicle-stimulating Hormone (FSH) | FSH (Day 10) | 0.04 IU/L |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Change From Baseline in Follicle-stimulating Hormone (FSH) | FSH (Day 1) | 0.10 IU/L |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Change From Baseline in Follicle-stimulating Hormone (FSH) | FSH (Day 10) | -0.01 IU/L |
Comparison: The mean change in FSH levels from Day 10 pre-treatment (prior to first dose) in the LutrePulse 10 μg/Pulse group was compared to placebo using an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.p-value: 0.877295% CI: [-0.39, 0.46]ANCOVA
Comparison: The mean change in FSH levels from Day 10 pre-treatment (prior to first dose) in the LutrePulse 15 μg/Pulse group was compared to placebo using an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.p-value: 0.780595% CI: [-0.44, 0.58]ANCOVA
Comparison: The mean change in FSH levels from Day 10 pre-treatment (prior to first dose) in the LutrePulse 20 μg/Pulse group was compared to placebo using an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.p-value: 0.609595% CI: [-0.35, 0.58]ANCOVA
Secondary
Change From Baseline in LH
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
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LutrePulse 10 µg/Pulse | Change From Baseline in LH | Day 1 | 1.85 IU/L |
| LutrePulse 10 µg/Pulse | Change From Baseline in LH | Day 10 | 0.00 IU/L |
| LutrePulse 15 µg/Pulse | Change From Baseline in LH | Day 10 | 0.58 IU/L |
| LutrePulse 15 µg/Pulse | Change From Baseline in LH | Day 1 | 7.90 IU/L |
| LutrePulse 20 µg/Pulse | Change From Baseline in LH | Day 1 | 5.15 IU/L |
| LutrePulse 20 µg/Pulse | Change From Baseline in LH | Day 10 | 0.03 IU/L |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Change From Baseline in LH | Day 1 | 0.05 IU/L |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Change From Baseline in LH | Day 10 | 0.00 IU/L |
Comparison: The mean change in LH levels from Day 10 pre-treatment (prior to first dose) in the LutrePulse 10 μg/Pulse group was compared to placebo using an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.p-value: 0.15295% CI: [-0.2, 1.22]ANCOVA
Comparison: The mean change in LH levels from Day 10 pre-treatment (prior to first dose) in the LutrePulse 15 μg/Pulse group was compared to placebo using an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.p-value: 0.022195% CI: [0.14, 1.72]ANCOVA
Comparison: The mean change in LH levels from Day 10 pre-treatment (prior to first dose) in the LutrePulse 20 μg/Pulse group was compared to placebo using an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.p-value: 0.031695% CI: [0.07, 1.44]ANCOVA
Secondary
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.
Time frame: 2 to 4 weeks after a second positive serum β-hCG test
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LutrePulse 10 µg/Pulse | Clinical Pregnancy Rate | 0 Participants |
| LutrePulse 15 µg/Pulse | Clinical Pregnancy Rate | 2 Participants |
| LutrePulse 20 µg/Pulse | Clinical Pregnancy Rate | 5 Participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Clinical Pregnancy Rate | 7 Participants |
| Placebo | Clinical Pregnancy Rate | 0 Participants |
Comparison: Clinical pregnancy rates of the pooled LutrePulse 15 μg and 20 μg group were compared to placebo.p-value: 0.0383Fisher Exact
Secondary
Estradiol (E2) Serum Levels
E2 serum levels on Day 1 and Day 10.
Time frame: At treatment Day 1 and Day 10
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LutrePulse 10 µg/Pulse | Estradiol (E2) Serum Levels | Day 1 (pre-dose) | 36.50 pmol/L |
| LutrePulse 10 µg/Pulse | Estradiol (E2) Serum Levels | Day 10 (pre-dose) | 106.00 pmol/L |
| LutrePulse 15 µg/Pulse | Estradiol (E2) Serum Levels | Day 10 (pre-dose) | 202.00 pmol/L |
| LutrePulse 15 µg/Pulse | Estradiol (E2) Serum Levels | Day 1 (pre-dose) | 88.00 pmol/L |
| LutrePulse 20 µg/Pulse | Estradiol (E2) Serum Levels | Day 10 (pre-dose) | 136.00 pmol/L |
| LutrePulse 20 µg/Pulse | Estradiol (E2) Serum Levels | Day 1 (pre-dose) | 81.00 pmol/L |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Estradiol (E2) Serum Levels | Day 1 (pre-dose) | 122.50 pmol/L |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Estradiol (E2) Serum Levels | Day 10 (pre-dose) | 128.00 pmol/L |
Comparison: The mean change in E2 levels from Day 10 pre-treatment (prior to first dose) in the LutrePulse 10 μg/Pulse group was compared to placebo using an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.p-value: 0.314795% CI: [-72.66, 218.65]ANCOVA
Comparison: The mean change in E2 levels from Day 10 pre-treatment (prior to first dose) in the LutrePulse 15 μg/Pulse group was compared to placebo using an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.p-value: 0.22995% CI: [-63.01, 253.36]ANCOVA
Comparison: The mean change in E2 levels from Day 10 pre-treatment (prior to first dose) in the LutrePulse 20 μg/Pulse group was compared to placebo using an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.p-value: 0.506695% CI: [-95.64, 189.61]ANCOVA
Secondary
Frequency and Severity of Ovarian Hyperstimulation Syndrome (OHSS)
Proportion of subjects reporting OHSS classified as mild, moderate, or severe.
Time frame: From treatment Day 1 to end-of-trial, approximately 10 weeks
Population: The safety analysis set comprised all randomized subjects who received at least one pulsatile delivery of IMP. The number count is based on the actual treatment subjects received: one subject randomized to LutrePulse 15 µg/Pulse had received placebo and was moved to the placebo group in the safety analysis set (LutrePulse 15 µg/Pulse: n=8, Placebo: n=11)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LutrePulse 10 µg/Pulse | Frequency and Severity of Ovarian Hyperstimulation Syndrome (OHSS) | 0 participants |
| LutrePulse 15 µg/Pulse | Frequency and Severity of Ovarian Hyperstimulation Syndrome (OHSS) | 0 participants |
| LutrePulse 20 µg/Pulse | Frequency and Severity of Ovarian Hyperstimulation Syndrome (OHSS) | 0 participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Frequency and Severity of Ovarian Hyperstimulation Syndrome (OHSS) | 0 participants |
Secondary
Hematology, Clinical Chemistry, and Urinalysis
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
Population: The safety analysis set comprised all randomized subjects who received at least one pulsatile delivery of IMP. The number count is based on the actual treatment subjects received: one subject randomized to LutrePulse 15 µg/Pulse had received placebo and was moved to the placebo group in the safety analysis set (LutrePulse 15 µg/Pulse: n=8, Placebo: n=11)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LutrePulse 10 µg/Pulse | Hematology, Clinical Chemistry, and Urinalysis | Hematology | 0 participants |
| LutrePulse 10 µg/Pulse | Hematology, Clinical Chemistry, and Urinalysis | Serum chemistry (Sodium, <=130 mmol/L) | 0 participants |
| LutrePulse 10 µg/Pulse | Hematology, Clinical Chemistry, and Urinalysis | Urinalysis (Protein,mg/dL, -ve to +ve [post-dose]) | 2 participants |
| LutrePulse 10 µg/Pulse | Hematology, Clinical Chemistry, and Urinalysis | Urinalysis (Specific Gravity <=1.005) | 0 participants |
| LutrePulse 15 µg/Pulse | Hematology, Clinical Chemistry, and Urinalysis | Serum chemistry (Sodium, <=130 mmol/L) | 1 participants |
| LutrePulse 15 µg/Pulse | Hematology, Clinical Chemistry, and Urinalysis | Urinalysis (Protein,mg/dL, -ve to +ve [post-dose]) | 0 participants |
| LutrePulse 15 µg/Pulse | Hematology, Clinical Chemistry, and Urinalysis | Urinalysis (Specific Gravity <=1.005) | 1 participants |
| LutrePulse 15 µg/Pulse | Hematology, Clinical Chemistry, and Urinalysis | Hematology | 0 participants |
| LutrePulse 20 µg/Pulse | Hematology, Clinical Chemistry, and Urinalysis | Urinalysis (Protein,mg/dL, -ve to +ve [post-dose]) | 1 participants |
| LutrePulse 20 µg/Pulse | Hematology, Clinical Chemistry, and Urinalysis | Serum chemistry (Sodium, <=130 mmol/L) | 0 participants |
| LutrePulse 20 µg/Pulse | Hematology, Clinical Chemistry, and Urinalysis | Urinalysis (Specific Gravity <=1.005) | 1 participants |
| LutrePulse 20 µg/Pulse | Hematology, Clinical Chemistry, and Urinalysis | Hematology | 0 participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Hematology, Clinical Chemistry, and Urinalysis | Urinalysis (Specific Gravity <=1.005) | 0 participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Hematology, Clinical Chemistry, and Urinalysis | Serum chemistry (Sodium, <=130 mmol/L) | 0 participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Hematology, Clinical Chemistry, and Urinalysis | Hematology | 0 participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Hematology, Clinical Chemistry, and Urinalysis | Urinalysis (Protein,mg/dL, -ve to +ve [post-dose]) | 0 participants |
Secondary
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.
Time frame: Daily from Day 11 until first positive LH surge or until Day 39
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LutrePulse 10 µg/Pulse | LH Surge Detection | 3 Participants |
| LutrePulse 15 µg/Pulse | LH Surge Detection | 7 Participants |
| LutrePulse 20 µg/Pulse | LH Surge Detection | 6 Participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | LH Surge Detection | 13 Participants |
| Placebo | LH Surge Detection | 0 Participants |
Comparison: LH surge detection of the pooled LutrePulse 15 μg and 20 μg group were compared to placebo.p-value: 0.0011Fisher Exact
Secondary
Luteal Phase Support: Maximum P4 Levels
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
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LutrePulse 10 µg/Pulse | Luteal Phase Support: Maximum P4 Levels | 0.40 ng/mL |
| LutrePulse 15 µg/Pulse | Luteal Phase Support: Maximum P4 Levels | 2.40 ng/mL |
| LutrePulse 20 µg/Pulse | Luteal Phase Support: Maximum P4 Levels | 8.00 ng/mL |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Luteal Phase Support: Maximum P4 Levels | 0.30 ng/mL |
Comparison: Maximum P4 levels in the LutrePulse 10 µg group were compared to placebo using an analysis of covariance (ANCOVA) model including the randomization scheme and treatment group as factors and baseline value as covariate.p-value: 0.673295% CI: [-5.16, 7.87]ANCOVA
Comparison: Maximum P4 levels in the LutrePulse 15 µg group were compared to placebo using an ANCOVA model including treatment group as factors and baseline value as covariate.p-value: 0.081495% CI: [-0.76, 12.15]ANCOVA
Comparison: Maximum P4 levels in the LutrePulse 20 µg group were compared to placebo using an ANCOVA model including the randomization scheme and treatment group as factors and baseline value as covariate.p-value: 0.022395% CI: [1.16, 13.93]ANCOVA
Secondary
Luteal Phase Support: Mean P4 Levels
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
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LutrePulse 10 µg/Pulse | Luteal Phase Support: Mean P4 Levels | 0.313 ng/mL |
| LutrePulse 15 µg/Pulse | Luteal Phase Support: Mean P4 Levels | 1.440 ng/mL |
| LutrePulse 20 µg/Pulse | Luteal Phase Support: Mean P4 Levels | 3.920 ng/mL |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Luteal Phase Support: Mean P4 Levels | 0.233 ng/mL |
Comparison: Mean P4 levels in the LutrePulse 10 µg group were compared to placebo using an ANCOVA model including the randomization scheme and treatment group as factors and baseline value as covariate.p-value: 0.735595% CI: [-3.404, 4.762]ANCOVA
Comparison: Mean P4 levels in the LutrePulse 15 µg group were compared to placebo using an ANCOVA model including treatment group as factors and baseline value as covariate.p-value: 0.19895% CI: [-1.444, 6.648]ANCOVA
Comparison: Mean P4 levels in the LutrePulse 20 µg group were compared to placebo using an ANCOVA model including the randomization scheme and treatment group as factors and baseline value as covariate.p-value: 0.018795% CI: [0.878, 8.882]ANCOVA
Secondary
Mean Serum FSH and LH Levels
Mean FSH and LH levels on Day 1 and Day 10.
Time frame: Treatment Days 1 and Day 10
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LutrePulse 10 µg/Pulse | Mean Serum FSH and LH Levels | FSH (Baseline) | 1.59 IU/L | Standard Deviation 1.793 |
| LutrePulse 10 µg/Pulse | Mean Serum FSH and LH Levels | FSH (Day 1) | 3.64 IU/L | Standard Deviation 4.01 |
| LutrePulse 10 µg/Pulse | Mean Serum FSH and LH Levels | FSH (Day 10) | 4.00 IU/L | Standard Deviation 1.495 |
| LutrePulse 10 µg/Pulse | Mean Serum FSH and LH Levels | LH (Baseline) | 0.54 IU/L | Standard Deviation 0.669 |
| LutrePulse 10 µg/Pulse | Mean Serum FSH and LH Levels | LH (Day 1) | 6.27 IU/L | Standard Deviation 9.507 |
| LutrePulse 10 µg/Pulse | Mean Serum FSH and LH Levels | LH (Day 10) | 4.12 IU/L | Standard Deviation 3.931 |
| LutrePulse 15 µg/Pulse | Mean Serum FSH and LH Levels | LH (Day 10) | 4.69 IU/L | Standard Deviation 2.692 |
| LutrePulse 15 µg/Pulse | Mean Serum FSH and LH Levels | LH (Baseline) | 0.27 IU/L | Standard Deviation 0.179 |
| LutrePulse 15 µg/Pulse | Mean Serum FSH and LH Levels | FSH (Baseline) | 1.47 IU/L | Standard Deviation 1.112 |
| LutrePulse 15 µg/Pulse | Mean Serum FSH and LH Levels | FSH (Day 10) | 5.07 IU/L | Standard Deviation 2.53 |
| LutrePulse 15 µg/Pulse | Mean Serum FSH and LH Levels | FSH (Day 1) | 6.20 IU/L | Standard Deviation 3.929 |
| LutrePulse 15 µg/Pulse | Mean Serum FSH and LH Levels | LH (Day 1) | 8.82 IU/L | Standard Deviation 7.348 |
| LutrePulse 20 µg/Pulse | Mean Serum FSH and LH Levels | FSH (Day 1) | 5.38 IU/L | Standard Deviation 2.565 |
| LutrePulse 20 µg/Pulse | Mean Serum FSH and LH Levels | FSH (Day 10) | 5.24 IU/L | Standard Deviation 1.124 |
| LutrePulse 20 µg/Pulse | Mean Serum FSH and LH Levels | LH (Baseline) | 0.93 IU/L | Standard Deviation 0.954 |
| LutrePulse 20 µg/Pulse | Mean Serum FSH and LH Levels | LH (Day 10) | 4.07 IU/L | Standard Deviation 2.335 |
| LutrePulse 20 µg/Pulse | Mean Serum FSH and LH Levels | LH (Day 1) | 6.12 IU/L | Standard Deviation 3.745 |
| LutrePulse 20 µg/Pulse | Mean Serum FSH and LH Levels | FSH (Baseline) | 2.48 IU/L | Standard Deviation 2.235 |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Mean Serum FSH and LH Levels | LH (Day 1) | 0.79 IU/L | Standard Deviation 1.026 |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Mean Serum FSH and LH Levels | LH (Day 10) | 0.82 IU/L | Standard Deviation 1.037 |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Mean Serum FSH and LH Levels | FSH (Day 1) | 1.52 IU/L | Standard Deviation 1.673 |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Mean Serum FSH and LH Levels | LH (Baseline) | 0.73 IU/L | Standard Deviation 1.063 |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Mean Serum FSH and LH Levels | FSH (Baseline) | 1.35 IU/L | Standard Deviation 1.52 |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Mean Serum FSH and LH Levels | FSH (Day 10) | 1.67 IU/L | Standard Deviation 1.796 |
Secondary
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.
Time frame: From treatment Day 10 to treatment Day 21
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LutrePulse 10 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 18 | 0.0 follicles |
| LutrePulse 10 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 12 | 0.0 follicles |
| LutrePulse 10 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 21 | 0.0 follicles |
| LutrePulse 10 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 15 | 0.0 follicles |
| LutrePulse 10 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 10 | 0.0 follicles |
| LutrePulse 15 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 15 | 0.0 follicles |
| LutrePulse 15 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 18 | 0.0 follicles |
| LutrePulse 15 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 21 | 0.0 follicles |
| LutrePulse 15 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 12 | 0.0 follicles |
| LutrePulse 15 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 10 | 0.0 follicles |
| LutrePulse 20 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 15 | 0.0 follicles |
| LutrePulse 20 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 10 | 0.0 follicles |
| LutrePulse 20 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 12 | 0.0 follicles |
| LutrePulse 20 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 18 | 0.0 follicles |
| LutrePulse 20 µg/Pulse | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 21 | 0.0 follicles |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 18 | 0.0 follicles |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 12 | 0.0 follicles |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 10 | 0.0 follicles |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 15 | 0.0 follicles |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm | Day 21 | 0.0 follicles |
Comparison: Day 12: Number of follicles with a mean diameter ≥18 mm in the LutrePulse 15 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.4142Wilcoxon rank sum test
Comparison: Number of follicles with a mean diameter ≥18 mm in the LutrePulse 20 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.2374Wilcoxon rank sum test
Comparison: Day 15: Number of follicles with a mean diameter ≥18 mm in the LutrePulse 10 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.2636Wilcoxon rank sum test
Comparison: Day 15: Number of follicles with a mean diameter ≥18 mm in the LutrePulse 15 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.4795Wilcoxon rank sum test
Comparison: Day 15: Number of follicles with a mean diameter ≥18 mm in the LutrePulse 20 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.3173Wilcoxon rank sum test
Comparison: Day 18: Number of follicles with a mean diameter ≥18 mm in the LutrePulse 10 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.3711Wilcoxon rank sum test
Comparison: Day 18: Number of follicles with a mean diameter ≥18 mm in the LutrePulse 15 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.4142Wilcoxon rank sum test
Comparison: Day 18: Number of follicles with a mean diameter ≥18 mm in the LutrePulse 20 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.0838Wilcoxon rank sum test
Comparison: Day 21: Number of follicles with a mean diameter ≥18 mm in the LutrePulse 10 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.3173Wilcoxon rank sum test
Comparison: Day 21: Number of follicles with a mean diameter ≥18 mm in the LutrePulse 15 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.3778Wilcoxon rank sum test
Secondary
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.
Time frame: From treatment Day 10 to treatment Day 21
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LutrePulse 10 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 18 | 0.0 follicles |
| LutrePulse 10 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 12 | 0.0 follicles |
| LutrePulse 10 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 21 | 0.0 follicles |
| LutrePulse 10 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 15 | 0.0 follicles |
| LutrePulse 10 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 10 | 0.0 follicles |
| LutrePulse 15 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 15 | 0.0 follicles |
| LutrePulse 15 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 18 | 1.0 follicles |
| LutrePulse 15 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 21 | 0.0 follicles |
| LutrePulse 15 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 12 | 0.5 follicles |
| LutrePulse 15 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 10 | 0.0 follicles |
| LutrePulse 20 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 15 | 0.0 follicles |
| LutrePulse 20 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 10 | 0.0 follicles |
| LutrePulse 20 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 12 | 0.0 follicles |
| LutrePulse 20 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 18 | 1.0 follicles |
| LutrePulse 20 µg/Pulse | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 21 | 0.0 follicles |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 18 | 0.0 follicles |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 12 | 0.0 follicles |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 10 | 0.0 follicles |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 15 | 0.0 follicles |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm | Day 21 | 0.0 follicles |
Comparison: Day 10: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 10 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.1344Wilcoxon rank sum test
Comparison: Day 10: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 15 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.2726Wilcoxon rank sum test
Comparison: Day 10: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 20 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.3173Wilcoxon rank sum test
Comparison: Day 12: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 10 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.1275Wilcoxon rank sum test
Comparison: Day 12: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 15 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.1088Wilcoxon rank sum test
Comparison: Day 12: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 20 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.2374Wilcoxon rank sum test
Comparison: Day 15: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 10 μg group was compared to placebo, using Wilcoxon's rank sum testp-value: 0.0796Wilcoxon rank sum test
Comparison: Day 15: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 15 μg group was compared to placebo, using Wilcoxon's rank sum testp-value: 0.1757Wilcoxon rank sum test
Comparison: Day 15: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 20 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.0584Wilcoxon rank sum test
Comparison: Day 18: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 10 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.3711Wilcoxon rank sum test
Comparison: Day 18: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 15 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.0143Wilcoxon rank sum test
Comparison: Day 18: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 20 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.006Wilcoxon rank sum test
Comparison: Day 21: Number of follicles with a mean diameter ≥14 mm in the LutrePulse 20 μg group was compared to placebo, using Wilcoxon's rank sum test.p-value: 0.1573Wilcoxon rank sum test
Secondary
Progesterone (P4) Levels
Proportion of participants with at least 1 post-baseline P4 level ≥ 10 ng/mL.
Time frame: Treatment Days 19, 21, 23, 25, and 27
Population: The full analysis set (FAS) comprised all randomized subjects who were included in ITT analysis set and had received at least 14 days of investigational medicinal product (IMP). One subject in the LutrePulse 10 µg/Pulse group was discontinued from the trial after 6 days exposure and is not included in the FAS (LutrePulse 10 µg/Pulse: n=9).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LutrePulse 10 µg/Pulse | Progesterone (P4) Levels | 1 Participants |
| LutrePulse 15 µg/Pulse | Progesterone (P4) Levels | 4 Participants |
| LutrePulse 20 µg/Pulse | Progesterone (P4) Levels | 3 Participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Progesterone (P4) Levels | 7 Participants |
| Placebo | Progesterone (P4) Levels | 0 Participants |
Comparison: P4 levels of the pooled LutrePulse 15 μg and 20 μg group were compared to placebo.p-value: 0.0553Fisher Exact
Secondary
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.
Time frame: From treatment Day 1 to end-of-trial, approximately 10 weeks
Population: The safety analysis set comprised all randomized subjects who received at least one pulsatile delivery of IMP. The number count is based on the actual treatment subjects received: one subject randomized to LutrePulse 15 µg/Pulse had received placebo and was moved to the placebo group in the safety analysis set (LutrePulse 15 µg/Pulse: n=8, Placebo: n=11)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LutrePulse 10 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Any AE | 5 Participants |
| LutrePulse 10 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Non-serious AE | 5 Participants |
| LutrePulse 10 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Serious AE | 0 Participants |
| LutrePulse 10 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Intensity (Mild) | 5 Participants |
| LutrePulse 10 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Intensity (Moderate) | 0 Participants |
| LutrePulse 10 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Intensity (Severe) | 0 Participants |
| LutrePulse 15 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Intensity (Severe) | 0 Participants |
| LutrePulse 15 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Intensity (Mild) | 1 Participants |
| LutrePulse 15 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Any AE | 3 Participants |
| LutrePulse 15 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Serious AE | 0 Participants |
| LutrePulse 15 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Non-serious AE | 3 Participants |
| LutrePulse 15 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Intensity (Moderate) | 2 Participants |
| LutrePulse 20 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Non-serious AE | 4 Participants |
| LutrePulse 20 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Serious AE | 0 Participants |
| LutrePulse 20 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Intensity (Mild) | 2 Participants |
| LutrePulse 20 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Intensity (Severe) | 0 Participants |
| LutrePulse 20 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Intensity (Moderate) | 2 Participants |
| LutrePulse 20 µg/Pulse | Type, Intensity, and Frequency of Adverse Events (AEs) | Any AE | 4 Participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Type, Intensity, and Frequency of Adverse Events (AEs) | Intensity (Moderate) | 2 Participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Type, Intensity, and Frequency of Adverse Events (AEs) | Intensity (Severe) | 1 Participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Type, Intensity, and Frequency of Adverse Events (AEs) | Non-serious AE | 4 Participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Type, Intensity, and Frequency of Adverse Events (AEs) | Intensity (Mild) | 1 Participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Type, Intensity, and Frequency of Adverse Events (AEs) | Any AE | 4 Participants |
| Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled | Type, Intensity, and Frequency of Adverse Events (AEs) | Serious AE | 0 Participants |