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CompletedNCT01976728Updated Mar 3, 2021Results posted

LutrePulse Hypogonadotropic Hypogonadism

A Phase 3 interventional study of Gonadorelin acetate subcutaneous (SC) 10 μg/pulse as a fixed dose, administered via. OmniPod pump and Gonadorelin acetate SC 15 μg/pulse as a fixed dose, administered via. OmniPod pump in Primary Amenorrhea With Hypogonadotropic Hypogonadism, sponsored by Ferring Pharmaceuticals. Completed at 35 sites in 2 countries. Open to female participants aged 18 Years to 40 Years. Per ClinicalTrials.gov, last updated 2021-03-03.

Sponsored by Ferring Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
39
Allocation
Randomized
Ages
18 Years to 40 Years
Sex
Female
01

Study 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

02

Conditions studied

  • Primary Amenorrhea With Hypogonadotropic Hypogonadism
03

In context

Hypogonadism

345 studies on the registry are indexed under Hypogonadism; 43 are open to participants now.

This study's enrollment of 39 is below the median of 56 across 260 interventional studies indexed under Hypogonadism.

Browse Hypogonadism studies →

Lead sponsor

Ferring Pharmaceuticals is the lead sponsor of 244 studies on the registry; 4 are open to participants now.

Of its 14 completed or terminated interventional studies of FDA-regulated products, 13 (93%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 40 Years
Sexes eligible
Female
Accepts 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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
39 participants (actual)

Study arms

  • Experimental
    LutrePulse 10 µg/pulse

    Gonadorelin acetate 10 µg/pulse

    Drug: Gonadorelin acetate subcutaneous (SC) 10 μg/pulse as a fixed dose, administered via. OmniPod pump

  • Experimental
    LutrePulse 15 µg/pulse

    Gonadorelin acetate 15 µg/pulse

    Drug: Gonadorelin acetate SC 15 μg/pulse as a fixed dose, administered via. OmniPod pump

  • Experimental
    LutrePulse 20 µg/pulse

    Gonadorelin acetate 20 µg/pulse

    Drug: Gonadorelin acetate SC 20 μg/pulse as a fixed dose, administered via. OmniPod pump

  • Placebo comparator
    Placebo

    Placebo

    Drug: Placebo (SC 10, 15, or 20 μg/pulse as a fixed dose, administered via. OmniPod pump)

Interventions

  • DrugGonadorelin acetate subcutaneous (SC) 10 μg/pulse as a fixed dose, administered via. OmniPod pump

    Also known as: LutrePulse

  • DrugGonadorelin acetate SC 15 μg/pulse as a fixed dose, administered via. OmniPod pump

    Also known as: LutrePulse

  • DrugGonadorelin acetate SC 20 μg/pulse as a fixed dose, administered via. OmniPod pump

    Also known as: LutrePulse

  • DrugPlacebo (SC 10, 15, or 20 μg/pulse as a fixed dose, administered via. OmniPod pump)
06

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Estradiol (E2) Serum Levels

    E2 serum levels on Day 1 and Day 10.

    Time frame: At treatment Day 1 and Day 10

  13. 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

  14. 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

  15. 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

07

Results

Posted Mar 3, 2021

Participant flow

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.

Participant flow — Overall Study
MilestoneLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
Started1091010
Dosed1091010
Completed991010
Not completed1000
Withdrew: Subject missed multiple doses of imp1000

Outcome measures

PrimaryOvulation 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
Reported as:
Count of participants · Participants
Ovulation Rate
ParticipantsLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulseLutrepulse 15 μg/Pulse and 20 μg/Pulse PooledPlacebo
Ovulation Rate14590
Statistical analysis
  • Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled vs Placebo · Fisher Exact · p = 0.0120 (The SAS PROC FREQ with permutation-based Cochran-Mantel-Haenszel test with exact p-value derived from all possible permutations was employed for the calculation of p-value for the stratified Fisher's exact test.)The success threshold at each analysis corresponded to a nominal p-value \<0.0130 to maintain an overall one-sided type I error rate of 0.025.
SecondaryProgesterone (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
Reported as:
Count of participants · Participants
Progesterone (P4) Levels
ParticipantsLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulseLutrepulse 15 μg/Pulse and 20 μg/Pulse PooledPlacebo
Progesterone (P4) Levels14370
Statistical analysis
  • Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled vs Placebo · Fisher Exact · p = 0.0553 (The SAS PROC FREQ with permutation-based Cochran-Mantel-Haenszel test with exact p-value derived from all possible permutations was employed for the calculation of p-value for the stratified Fisher's exact test.)The success threshold at each analysis corresponded to a nominal p-value \<0.0130 to maintain an overall one-sided type I error rate of 0.025.
SecondaryClinical 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
Reported as:
Count of participants · Participants
Clinical Pregnancy Rate
ParticipantsLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulseLutrepulse 15 μg/Pulse and 20 μg/Pulse PooledPlacebo
Clinical Pregnancy Rate02570
Statistical analysis
  • Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled vs Placebo · Fisher Exact · p = 0.0383 (The SAS PROC FREQ with permutation-based Cochran-Mantel-Haenszel test with exact p-value derived from all possible permutations was employed for the calculation of p-value for the stratified Fisher's exact test.)The success threshold at each analysis corresponded to a nominal p-value \<0.0130 to maintain an overall one-sided type I error rate of 0.025.
SecondaryBiochemical 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
Reported as:
Count of participants · Participants
Biochemical Pregnancy Rate
ParticipantsLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulseLutrepulse 15 μg/Pulse and 20 μg/Pulse PooledPlacebo
Biochemical Pregnancy Rate03580
Statistical analysis
  • Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled vs Placebo · Fisher Exact · p = 0.0246 (The SAS PROC FREQ with permutation-based Cochran-Mantel-Haenszel test with exact p-value derived from all possible permutations was employed for the calculation of p-value for the stratified Fisher's exact test.)The success threshold at each analysis corresponded to a nominal p-value \<0.0130 to maintain an overall one-sided type I error rate of 0.025.
SecondaryLH 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
Reported as:
Count of participants · Participants
LH Surge Detection
ParticipantsLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulseLutrepulse 15 μg/Pulse and 20 μg/Pulse PooledPlacebo
LH Surge Detection376130
Statistical analysis
  • Lutrepulse 15 μg/Pulse and 20 μg/Pulse Pooled vs Placebo · Fisher Exact · p = 0.0011 (The SAS PROC FREQ with permutation-based Cochran-Mantel-Haenszel test with exact p-value derived from all possible permutations was employed for the calculation of p-value for the stratified Fisher's exact test.)The success threshold at each analysis corresponded to a nominal p-value \<0.0130 to maintain an overall one-sided type I error rate of 0.025.
SecondaryOvarian 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
Reported as:
Median · follicles
Ovarian Follicular Development: Number of Follicles With a Mean Diameter Greater Than or Equal to (≥)14 mm
folliclesLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
Day 100.0 (0 to 2)0.0 (0 to 1)0.0 (0 to 1)0.0 (0 to 0)
Day 120.0 (0 to 1)0.5 (0 to 1)0.0 (0 to 1)0.0 (0 to 0)
Day 150.0 (0 to 1)0.0 (0 to 1)0.0 (0 to 1)0.0 (0 to 0)
Day 180.0 (0 to 1)1.0 (0 to 1)1.0 (0 to 2)0.0 (0 to 0)
Day 210.0 (0 to 0)0.0 (0 to 0)0.0 (0 to 1)0.0 (0 to 0)
Statistical analysis
  • LutrePulse 10 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.1344 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 15 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.2726 (The p-value was based on the Wilcoxon rank sum test without stratification.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 20 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.3173 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 10 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.1275 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 15 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.1088 (The p-value was based on the Wilcoxon rank sum test without stratification.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 20 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.2374 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 10 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.0796 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 15 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.1757 (The p-value was based on the Wilcoxon rank sum test without stratification.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 20 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.0584 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 10 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.3711 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 15 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.0143 (The p-value was based on the Wilcoxon rank sum test without stratification.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 20 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.0060 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 20 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.1573 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
SecondaryOvarian 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
Reported as:
Median · follicles
Ovarian Follicular Development: Number of Dominant Follicles With a Mean Diameter of ≥18 mm
folliclesLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
Day 100.0 (0 to 0)0.0 (0 to 0)0.0 (0 to 0)0.0 (0 to 0)
Day 120.0 (0 to 0)0.0 (0 to 1)0.0 (0 to 1)0.0 (0 to 0)
Day 150.0 (0 to 1)0.0 (0 to 1)0.0 (0 to 1)0.0 (0 to 0)
Day 180.0 (0 to 1)0.0 (0 to 1)0.0 (0 to 1)0.0 (0 to 0)
Day 210.0 (0 to 1)0.0 (0 to 1)0.0 (0 to 0)0.0 (0 to 0)
Statistical analysis
  • LutrePulse 15 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.4142 (The p-value was based on the Wilcoxon rank sum test without stratification.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 20 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.2374 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 10 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.2636 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 15 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.4795 (The p-value was based on the Wilcoxon rank sum test without stratification.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 20 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.3173 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 10 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.3711 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 15 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.4142 (The p-value was based on the Wilcoxon rank sum test without stratification.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 20 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.0838 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 10 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.3173 (The p-value was based on the stratified (by randomization scheme) Wilcoxon rank sum test.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
  • LutrePulse 15 µg/Pulse vs Placebo · Wilcoxon rank sum test · p = 0.3778 (The p-value was based on the Wilcoxon rank sum test without stratification.)SAS PROC FREQ with modified ridit score (MODRIDIT option) was used for the stratified Wilcoxon rank sum test.
SecondaryLuteal 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
Reported as:
Median · ng/mL
Luteal Phase Support: Maximum P4 Levels
ng/mLLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
Luteal Phase Support: Maximum P4 Levels0.40 (0.1 to 12.9)2.40 (0.4 to 18.5)8.00 (0.1 to 21.7)0.30 (0.1 to 0.4)
Statistical analysis
  • LutrePulse 10 µg/Pulse vs Placebo · ANCOVA · p = 0.6732 (p-value for the LutrePulse 10 µg group compared to placebo based on the fitted linear model were reported.) · Least square mean (lsm) difference: 1.35 · 95% CI -5.16 to 7.87The LSM difference on the treatment groups and 95% confidence interval (CI) for the LutrePulse 10 µg group compared to placebo based on the fitted linear model were reported. Type III sum-of-squares for the LSMs were used for statistical comparisons.
  • LutrePulse 15 µg/Pulse vs Placebo · ANCOVA · p = 0.0814 (p-value for the LutrePulse 15 µg group compared to placebo based on the fitted linear model were reported.) · Lsm: 5.70 · 95% CI -0.76 to 12.15The LSM difference on the treatment groups and 95% CI for the LutrePulse 15 µg group compared to placebo based on the fitted linear model were reported. Type III sum-of-squares for the LSMs were used for statistical comparisons.
  • LutrePulse 20 µg/Pulse vs Placebo · ANCOVA · p = 0.0223 (p-value for the LutrePulse 20 µg group compared to placebo based on the fitted linear model were reported.) · Lsm difference: 7.55 · 95% CI 1.16 to 13.93The LSM difference on the treatment groups and 95% CI for the LutrePulse 20 µg group compared to placebo based on the fitted linear model were reported. Type III sum-of-squares for the LSMs were used for statistical comparisons.
SecondaryLuteal 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
Reported as:
Median · ng/mL
Luteal Phase Support: Mean P4 Levels
ng/mLLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
Luteal Phase Support: Mean P4 Levels0.313 (0.10 to 8.06)1.440 (0.26 to 8.50)3.920 (0.10 to 14.80)0.233 (0.10 to 0.40)
Statistical analysis
  • LutrePulse 10 µg/Pulse vs Placebo · ANCOVA · p = 0.7355 (p-value for the LutrePulse 10 µg group compared to placebo based on the fitted linear model were reported.) · Lsm difference: 0.679 · 95% CI -3.404 to 4.762The LSM difference on the treatment groups and 95% CI for the LutrePulse 10 µg group compared to placebo based on the fitted linear model were reported. Type III sum-of-squares for the LSMs were used for statistical comparisons.
  • LutrePulse 15 µg/Pulse vs Placebo · ANCOVA · p = 0.1980 (p-value for the LutrePulse 15 µg group compared to placebo based on the fitted linear model were reported.) · Lsm difference: 2.602 · 95% CI -1.444 to 6.648The LSM difference on the treatment groups and 95% CI for the LutrePulse 15 µg group compared to placebo based on the fitted linear model were reported. Type III sum-of-squares for the LSMs were used for statistical comparisons.
  • LutrePulse 20 µg/Pulse vs Placebo · ANCOVA · p = 0.0187 (p-value for the LutrePulse 10 µg group compared to placebo based on the fitted linear model were reported.) · Lsm difference: 4.880 · 95% CI 0.878 to 8.882The LSM difference on the treatment groups and 95% CI for the LutrePulse 20 µg group compared to placebo based on the fitted linear model were reported. Type III sum-of-squares for the LSMs were used for statistical comparisons.
SecondaryChange 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
Reported as:
Median · IU/L
Change From Baseline in Follicle-stimulating Hormone (FSH)
IU/LLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
FSH (Day 1)1.30 (0.0 to 7.7)5.40 (0.0 to 9.9)2.70 (0.0 to 5.7)0.10 (0.0 to 0.6)
FSH (Day 10)0.04 (-0.8 to 0.8)-0.04 (-0.3 to 0.4)0.04 (-0.7 to 0.6)-0.01 (-0.1 to 0.1)
Statistical analysis
  • LutrePulse 10 µg/Pulse vs Placebo · ANCOVA · p = 0.8772 (The p-value was derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.) · Lsm difference: 0.03 · 95% CI -0.39 to 0.46LSM difference and CIs were derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.
  • LutrePulse 15 µg/Pulse vs Placebo · ANCOVA · p = 0.7805 (The p-value was derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.) · Lsm difference: 0.07 · 95% CI -0.44 to 0.58LSM difference and CIs were derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.
  • LutrePulse 20 µg/Pulse vs Placebo · ANCOVA · p = 0.6095 (The p-value was derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.) · Lsm difference: 0.12 · 95% CI -0.35 to 0.58LSM difference and CIs were derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.
SecondaryChange 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
Reported as:
Median · IU/L
Change From Baseline in LH
IU/LLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
Day 11.85 (0.2 to 22.6)7.90 (0.4 to 23.6)5.15 (0.6 to 12.4)0.05 (-0.2 to 0.3)
Day 100.00 (-2.9 to 1.6)0.58 (-1.7 to 1.9)0.03 (-0.9 to 1.7)0.00 (-1.0 to 0.0)
Statistical analysis
  • LutrePulse 10 µg/Pulse vs Placebo · ANCOVA · p = 0.1520 (The p-value was derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.) · Lsm difference: 0.51 · 95% CI -0.20 to 1.22LSM difference and CIs were derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.
  • LutrePulse 15 µg/Pulse vs Placebo · ANCOVA · p = 0.0221 (The p-value was derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.) · Lsm difference: 0.93 · 95% CI 0.14 to 1.72LSM difference and CIs were derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.
  • LutrePulse 20 µg/Pulse vs Placebo · ANCOVA · p = 0.0316 (The p-value was derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.) · Lsm difference: 0.76 · 95% CI 0.07 to 1.44LSM difference and CIs were derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.
SecondaryMean Serum FSH and LH Levels

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

Time frame:
Treatment Days 1 and Day 10
Reported as:
Mean · IU/L
Mean Serum FSH and LH Levels
IU/LLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
FSH (Baseline)1.59 ± 1.7931.47 ± 1.1122.48 ± 2.2351.35 ± 1.520
FSH (Day 1)3.64 ± 4.0106.20 ± 3.9295.38 ± 2.5651.52 ± 1.673
FSH (Day 10)4.00 ± 1.4955.07 ± 2.5305.24 ± 1.1241.67 ± 1.796
LH (Baseline)0.54 ± 0.6690.27 ± 0.1790.93 ± 0.9540.73 ± 1.063
LH (Day 1)6.27 ± 9.5078.82 ± 7.3486.12 ± 3.7450.79 ± 1.026
LH (Day 10)4.12 ± 3.9314.69 ± 2.6924.07 ± 2.3350.82 ± 1.037
SecondaryEstradiol (E2) Serum Levels

E2 serum levels on Day 1 and Day 10.

Time frame:
At treatment Day 1 and Day 10
Reported as:
Median · pmol/L
Estradiol (E2) Serum Levels
pmol/LLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
Day 1 (pre-dose)36.50 (36.5 to 169.0)88.00 (36.5 to 147.0)81.00 (36.5 to 92.0)122.50 (36.5 to 198.0)
Day 10 (pre-dose)106.00 (36.5 to 697.0)202.00 (84.0 to 499.0)136.00 (36.5 to 323.0)128.00 (36.5 to 224.0)
Statistical analysis
  • LutrePulse 10 µg/Pulse vs Placebo · ANCOVA · p = 0.3147 (The p-value was derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.) · Lsm difference: 73.00 · 95% CI -72.66 to 218.65LSM difference and CIs were derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.
  • LutrePulse 15 µg/Pulse vs Placebo · ANCOVA · p = 0.2290 (The p-value was derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.) · Lsm difference: 95.18 · 95% CI -63.01 to 253.36LSM difference and CIs were derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.
  • LutrePulse 20 µg/Pulse vs Placebo · ANCOVA · p = 0.5066 (The p-value was derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.) · Lsm difference: 46.99 · 95% CI -95.64 to 189.61LSM difference and CIs were derived from an ANCOVA model with randomization scheme and treatment as factors and baseline value as covariate.
SecondaryType, 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
Reported as:
Count of participants · Participants
Type, Intensity, and Frequency of Adverse Events (AEs)
ParticipantsLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
Any AE5344
Non-serious AE5344
Serious AE0000
Intensity (Mild)5121
Intensity (Moderate)0222
Intensity (Severe)0001
SecondaryHematology, 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
Reported as:
Number · participants
Hematology, Clinical Chemistry, and Urinalysis
participantsLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
Hematology0000
Serum chemistry (Sodium, <=130 mmol/L)0100
Urinalysis (Protein,mg/dL, -ve to +ve [post-dose])2010
Urinalysis (Specific Gravity <=1.005)0110
SecondaryFrequency 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
Reported as:
Number · participants
Frequency and Severity of Ovarian Hyperstimulation Syndrome (OHSS)
participantsLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
Frequency and Severity of Ovarian Hyperstimulation Syndrome (OHSS)0000

Adverse events

Collected over Treatment-emergent AEs (TEAEs) occurred after the start of IMP administration and within 5 days after the last dose, or a pre-treatment AE or pre-existing medical conditioning the worsened in intensity after the start of IMP and within 5 days after the last dose. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
LutrePulse 10 µg/Pulse0/10 (0%)0/10 (0%)5/10 (50%)
LutrePulse 15 µg/Pulse0/8 (0%)0/8 (0%)3/8 (37.5%)
LutrePulse 20 µg/Pulse0/10 (0%)0/10 (0%)4/10 (40%)
Placebo0/11 (0%)0/11 (0%)4/11 (36.4%)
Most frequent other events
Showing 10 of 31
Most frequent other events
EventLutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlacebo
Breast tendernessReproductive system and breast disorders0/102/82/100/11
Hot flushesVascular disorders0/101/82/100/11
Abdominal pain lowerGastrointestinal disorders0/101/80/100/11
NauseaGastrointestinal disorders0/101/81/100/11
HeadacheNervous system disorders1/101/80/100/11
Mood swingsPsychiatric disorders0/101/81/100/11
Adnexa uteri painReproductive system and breast disorders0/101/80/100/11
PruritusSkin and subcutaneous tissue disorders0/101/80/100/11
Abdominal discomfortGastrointestinal disorders0/100/81/100/11
Abdominal distesionGastrointestinal disorders0/100/81/101/11

Baseline characteristics

The intent-to-treat (ITT) analysis set comprised all randomized subjects.

Age, Continuous
Age, Continuous(years)LutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlaceboTotal
Mean30.9 ± 4.2029.6 ± 6.0230.9 ± 5.6729.5 ± 2.5530.2 ± 4.63
Sex: Female, Male
Sex: Female, Male(Participants)LutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlaceboTotal
Female109101039
Male00000
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)LutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlaceboTotal
Hispanic or Latino32139
Not Hispanic or Latino779730
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)LutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlaceboTotal
American Indian or Alaska Native00000
Asian01124
Native Hawaiian or Other Pacific Islander00000
Black or African American11204
White977831
More than one race00000
Unknown or Not Reported00000
BMI
BMI(kg/m^2)LutrePulse 10 µg/PulseLutrePulse 15 µg/PulseLutrePulse 20 µg/PulsePlaceboTotal
Mean29.41 ± 6.06523.70 ± 4.56726.53 ± 4.21823.85 ± 3.95325.93 ± 5.159
08

Study locations

35 sites
  • Fertility Treatment Center
    Tempe, Arizona, United States
  • Center for Reproductive Health UCSF
    San Francisco, California, United States
  • University of Colorado School of Medicine
    Aurora, Colorado, United States
  • Reproductive Associates of Delaware
    Newark, Delaware, United States
  • Columbia Fertility Associates
    Washington, District of Columbia, United States
  • Women's Medical Research Group, LLC
    Clearwater, Florida, United States
  • Center for Reproductive Medicine
    Orlando, Florida, United States
  • Georgia Reproductive Specialists
    Atlanta, Georgia, United States
  • Fertility Centers of Illinois
    Chicago, Illinois, United States
  • Cypress Medical Research Center
    Wichita, Kansas, United States
  • Bluegrass Clinical Research Inc.
    Louisville, Kentucky, United States
  • Maine Medical Center-REI
    Portland, Maine, United States
  • Massachusetts General Hospital
    Boston, Massachusetts, United States
  • Wayne State University Physicians Group
    Southfield, Michigan, United States
  • Weill Cornell Medical College
    New York, New York, United States
  • Carolinas HealthCare System
    Charlotte, North Carolina, United States
  • Lyndhurst Clinical Research
    Winston-Salem, North Carolina, United States
  • Wake Forest University Health Sciences
    Winston-Salem, North Carolina, United States
  • Institute for Reproductive Health
    Cincinnati, Ohio, United States
  • University of Cincinnati Physicians
    Cincinnati, Ohio, United States
  • UH Case Medical Center, MacDonald Clinical Trials
    Cleveland, Ohio, 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
  • Abington Reproductive Medicine, PC
    Abington, Pennsylvania, United States
  • Main Line Fertility Center
    Bryn Mawr, Pennsylvania, United States
  • Penn State MS Hershey Medical Center, Penn State College of Medicine
    Hershey, Pennsylvania, United States
  • University of Pittsburgh, Magee-Womens Hospital
    Pittsburgh, Pennsylvania, United States
  • Fertility Associates of Memphis PLLC
    Memphis, Tennessee, United States
  • Center for Assisted Reproduction
    Bedford, Texas, United States
  • Houston Fertility Institute
    Houston, Texas, United States
  • Center of Reproductive Medicine
    Webster, Texas, United States
  • Utah Fertility Center
    Pleasant Grove, Utah, United States
  • Jones Institute for Reproductive Medicine
    Norfolk, Virginia, United States
  • Olive Fertility Centre
    Vancouver, British Columbia, Canada
  • Ovo
    Montreal, Quebec, Canada
09

References and documents

Study documents

  • Study protocol · Dec 6, 2017
  • Statistical analysis plan · Dec 7, 2017

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 3, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01976728
Lead sponsor
Ferring Pharmaceuticals
Responsible party
Sponsor
First posted
Nov 6, 2013
Start date
Apr 1, 2014
Primary completion
Feb 23, 2018
Completion
Feb 23, 2018
Results posted
Mar 3, 2021
Last update
Mar 3, 2021

Study contacts

Global Clinical Compliance
study director · Ferring Pharmaceuticals

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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