Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 2 for:    MEGASET

MENOPUR® in a Gonadotropin-Releasing Hormone (GnRH) Antagonist Cycle With Single-Blastocyst Transfer in a High Responder Subject Population (MEGASET HR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02554279
Recruitment Status : Completed
First Posted : September 18, 2015
Results First Posted : March 2, 2018
Last Update Posted : March 20, 2019
Sponsor:
Information provided by (Responsible Party):
Ferring Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Infertility
Interventions Drug: menotropin
Drug: recombinant FSH
Enrollment 620
Recruitment Details The study was conducted at 31 infertility centers in the US between 31 Aug 2014 to 02 Feb 2017.
Pre-assignment Details  
Arm/Group Title Menotropin Recombinant FSH
Hide Arm/Group Description Menotropins for injection, provided as a vial with powder (75 international units [IU] follicle stimulating hormone [FSH] activity and 75 IU luteinizing hormone [LH] activity) and a vial with diluent. Follitropin alpha for injection, a human FSH preparation of recombinant deoxyribonucleic acid (DNA) origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Period Title: Overall Study
Started 311 309
Treated 310 309
Completed Day 6 of Stimulation 308 309
Received Trigger 293 307
Completed Oocyte Retrieval 292 306
Completed Fresh Blastocyst Transfer 201 191
Completed 279 291
Not Completed 32 18
Reason Not Completed
Adverse Event             2             5
Lost to Follow-up             3             2
Withdrawal by Subject             6             4
Protocol Violation             2             1
Other reason             19             6
Arm/Group Title Menotropin Recombinant FSH Total
Hide Arm/Group Description Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent. Follitropin alpha for injection, human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity. Total of all reporting groups
Overall Number of Baseline Participants 310 309 619
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 310 participants 309 participants 619 participants
30.0  (3.08) 30.4  (3.02) 30.2  (3.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 310 participants 309 participants 619 participants
Female
310
 100.0%
309
 100.0%
619
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 310 participants 309 participants 619 participants
American Indian or Alaska Native
1
   0.3%
1
   0.3%
2
   0.3%
Asian
18
   5.8%
33
  10.7%
51
   8.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
18
   5.8%
25
   8.1%
43
   6.9%
White
270
  87.1%
244
  79.0%
514
  83.0%
More than one race
1
   0.3%
4
   1.3%
5
   0.8%
Unknown or Not Reported
2
   0.6%
2
   0.6%
4
   0.6%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 310 participants 309 participants 619 participants
310
 100.0%
309
 100.0%
619
 100.0%
1.Primary Outcome
Title Ongoing Pregnancy Rate
Hide Description Defined as the percentage of participants with the presence of at least 1 intrauterine pregnancy with a detectable fetal heartbeat at 10-11 weeks of gestation.
Time Frame 8-9 weeks after blastocyst transfer in the fresh cycle
Hide Outcome Measure Data
Hide Analysis Population Description
The modified intent-to-treat (mITT) analysis set comprised all randomized participants who received at least 1 dose of investigational medicinal product.
Arm/Group Title Menotropin Recombinant FSH
Hide Arm/Group Description:
Menotropins for injection, provided as a vial with powder (75 IU activity and 75 IU LH activity) and a vial with diluent.
Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Overall Number of Participants Analyzed 310 309
Measure Type: Number
Unit of Measure: percentage of participants
35.5 30.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotropin, Recombinant FSH
Comments Null hypothesis was defined as the difference between ongoing pregnancy rate of participants randomized and treated with menotropin and recombinant FSH, as ≤-12%.
Type of Statistical Test Non-Inferiority
Comments The study had at least 80% power, to demonstrate the non-inferiority of menotropin to recombinant FSH at 1-sided significance level of 0.025 with a -12% non-inferiority margin.
Method of Estimation Estimation Parameter Absolute difference
Estimated Value 4.7
Confidence Interval (2-Sided) 95%
-2.7 to 12.1
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Positive β-human Chorionic Gonadotropin (hCG) Rate
Hide Description Defined as the percentage of participants with 2 positive β-hCG tests within 2 days in serum.
Time Frame First test approximately 10-14 days after blastocyst transfer in the fresh cycle, with a second test approximately 2 days later if first test was positive
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set comprised all randomized participants who received at least 1 dose of investigational medicinal product.
Arm/Group Title Menotropin Recombinant FSH
Hide Arm/Group Description:
Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Overall Number of Participants Analyzed 310 309
Measure Type: Number
Unit of Measure: percentage of participants
40.6 39.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotropin, Recombinant FSH
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Absolute difference
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-6.6 to 8.9
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Clinical Pregnancy Rate
Hide Description Defined as percentage of participants with transvaginal ultrasound (TVUS) showing at least 1 intrauterine gestational sac with fetal heart beat at 6-7 weeks of gestation.
Time Frame 4-5 weeks after blastocyst transfer in the fresh cycle
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set comprised all randomized participants who received at least 1 dose of investigational medicinal product.
Arm/Group Title Menotropin Recombinant FSH
Hide Arm/Group Description:
Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Overall Number of Participants Analyzed 310 309
Measure Type: Number
Unit of Measure: percentage of participants
37.1 33.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotropin, Recombinant FSH
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Absolute difference
Estimated Value 3.8
Confidence Interval (2-Sided) 95%
-3.8 to 11.3
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Early Pregnancy Loss
Hide Description Defined as participants with 2 positive β-hCG tests but no ongoing pregnancy at 10-11 weeks of gestation in the fresh cycle. Percentage of participants with early pregnancy loss is presented.
Time Frame At 10-11 weeks of gestation in the fresh cycle
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set comprised all randomized participants who received at least 1 dose of investigational medicinal product.
Arm/Group Title Menotropin Recombinant FSH
Hide Arm/Group Description:
Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Overall Number of Participants Analyzed 126 122
Measure Type: Number
Unit of Measure: percentage of participants
14.3 23.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotropin, Recombinant FSH
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Absolute difference
Estimated Value -9.5
Confidence Interval (2-Sided) 95%
-19.2 to 0.2
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Follicular Development as Assessed by TVUS
Hide Description Defined as average follicle size and average size of 3 largest follicles.
Time Frame On stimulation Day 6 and last day of stimulation (a maximum of 20 stimulation days)
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set comprised all randomized participants who received at least 1 dose of investigational medicinal product.
Arm/Group Title Menotropin, Stimulation Day 6 Recombinant FSH, Stimulation Day 6 Menotropin, Last Stimulation Day Recombinant FSH, Last Stimulation Day
Hide Arm/Group Description:
Menotropins for injection at stimulation Day 6. Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
Recombinant FSH at stimulation Day 6. Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Menotropin at last stimulation day. Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
Recombinant FSH at last stimulation day. Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity
Overall Number of Participants Analyzed 309 309 278 296
Mean (Standard Deviation)
Unit of Measure: mm
Average follicle size 5.95  (1.682) 7.45  (2.044) 12.20  (3.328) 13.28  (2.808)
Average size of 3 largest follicles 9.69  (3.562) 12.17  (2.590) 21.36  (2.524) 21.09  (2.685)
6.Secondary Outcome
Title Follicular Development as Assessed by TVUS
Hide Description Defined as percentage of participants with follicles having a diameter of ≤9 mm, 10-11 mm, 12-14 mm, 15-16 mm, and ≥17 mm.
Time Frame On stimulation Day 6 and last day of stimulation (a maximum of 20 stimulation days)
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set comprised all randomized participants who received at least 1 dose of investigational medicinal product.
Arm/Group Title Menotropin, Stimulation Day 6 Recombinant FSH, Stimulation Day 6 Menotropin, Last Stimulation Day Recombinant FSH, Last Stimulation Day
Hide Arm/Group Description:
Menotropins for injection at stimulation Day 6. Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
Recombinant FSH at stimulation Day 6. Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Menotropin at last stimulation day. Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
recombinant FSH at last stimulation day. Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Overall Number of Participants Analyzed 309 309 278 296
Measure Type: Number
Unit of Measure: percentage of participants
Follicle size ≤9 mm 99.0 96.4 78.4 69.9
Follicle size 10-11 mm 73.8 93.2 82.7 75.7
Follicle size 12-14 mm 50.2 76.1 93.5 96.6
Follicle size 15-16 mm 12.6 24.9 84.9 96.3
Follicle size ≥17 mm 5.2 9.7 100 100
7.Secondary Outcome
Title Number of Oocytes Retrieved
Hide Description [Not Specified]
Time Frame At oocyte retrieval visit (approximately 36 hours after hCG administration)
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set comprised all randomized participants who received at least 1 dose of investigational medicinal product. The number of participants analyzed represent the participants with oocytes retrieved.
Arm/Group Title Menotropin Recombinant FSH
Hide Arm/Group Description:
Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
Follitropin alpha for injection, human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Overall Number of Participants Analyzed 292 306
Mean (Standard Deviation)
Unit of Measure: oocytes
15.1  (10.12) 22.2  (11.54)
8.Secondary Outcome
Title Number of Metaphase II Oocytes
Hide Description [Not Specified]
Time Frame At oocyte retrieval visit (approximately 36 hours after hCG administration)
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set comprised all randomized participants who received at least 1 dose of investigational medicinal product. The number of participants analyzed represent the participants with oocytes retrieved.
Arm/Group Title Menotropin Recombinant FSH
Hide Arm/Group Description:
Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
Follitropin alpha for injection, human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Overall Number of Participants Analyzed 292 306
Mean (Standard Deviation)
Unit of Measure: metaphase II oocytes
10.1  (7.18) 15.9  (9.01)
9.Secondary Outcome
Title Fertilization Rate
Hide Description Defined as 100 times the ratio of number of fertilized 2 pronuclei oocytes to the number of oocytes retrieved, for each participant.
Time Frame On day 1 post-insemination
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set comprised all randomized participants who received at least 1 dose of investigational medicinal product.
Arm/Group Title Menotropin Recombinant FSH
Hide Arm/Group Description:
Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Overall Number of Participants Analyzed 289 305
Mean (Standard Deviation)
Unit of Measure: percentage of each participant
55.09  (21.731) 59.07  (18.731)
10.Secondary Outcome
Title Quality of Embryos
Hide Description Assessed by blastomere uniformity, cell size, the degree of fragmentation, and visual signs of multinucleation.
Time Frame 3 days after oocyte retrieval
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set comprised all randomized participants who received at least 1 dose of investigational medicinal product.
Arm/Group Title Menotropin Recombinant FSH
Hide Arm/Group Description:
Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Overall Number of Participants Analyzed 310 309
Overall Number of Units Analyzed
Type of Units Analyzed: Total number of embryos
2409 4028
Measure Type: Number
Unit of Measure: percentage of embryos
Blastomere uniformity-Equally sized blastomeres 63.1 59.0
Cell size classification-Stage specific 75.5 70.8
Degree of fragmentation-≤10% 81.1 81.0
Multinucleation present 0.7 1.1
11.Secondary Outcome
Title Quality of Embryos
Hide Description Assessed by cleavage stage.
Time Frame 3 days after oocyte retrieval
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set comprised all randomized participants who received at least 1 dose of investigational medicinal product.
Arm/Group Title Menotropin Recombinant FSH
Hide Arm/Group Description:
Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Overall Number of Participants Analyzed 310 309
Overall Number of Units Analyzed
Type of Units Analyzed: Total number of blastomere
2380 4001
Mean (Standard Deviation)
Unit of Measure: blastomeres
7.5  (2.28) 7.4  (2.32)
12.Secondary Outcome
Title Quality of Blastocysts
Hide Description Assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring was based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cell).
Time Frame 5 days after oocyte retrieval
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set comprised all randomized participants who received at least 1 dose of investigational medicinal product.
Arm/Group Title Menotropin Recombinant FSH
Hide Arm/Group Description:
Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent.
Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
Overall Number of Participants Analyzed 310 309
Overall Number of Units Analyzed
Type of Units Analyzed: Embryos reaching blastocyst stage
1338 2075
Measure Type: Number
Unit of Measure: percentage of embryos
Excellent quality 28.3 30.7
Good quality 26.5 22.5
Neither 45.1 45.8
Missing 0.1 1.0
Time Frame Adverse events were monitored from the time of obtaining informed consent until the last visit (end of trial).
Adverse Event Reporting Description Adverse events with onset after start of the first investigational medicinal product administration were considered treatment-emergent and are presented.
 
Arm/Group Title Menotropin Recombinant FSH
Hide Arm/Group Description Menotropins for injection, provided as a vial with powder (75 IU FSH activity and 75 IU LH activity) and a vial with diluent. Follitropin alpha for injection, a human FSH preparation of recombinant DNA origin, provided as pen and cartridges filled with either 300 or 450 IU of FSH activity.
All-Cause Mortality
Menotropin Recombinant FSH
Affected / at Risk (%) Affected / at Risk (%)
Total   0/310 (0.00%)   0/309 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Menotropin Recombinant FSH
Affected / at Risk (%) Affected / at Risk (%)
Total   8/310 (2.58%)   11/309 (3.56%) 
General disorders     
Pyrexia  1  1/310 (0.32%)  0/309 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis  1  0/310 (0.00%)  2/309 (0.65%) 
Cholecystitis  1  0/310 (0.00%)  1/309 (0.32%) 
Infections and infestations     
Sepsis  1  1/310 (0.32%)  0/309 (0.00%) 
Tubo-ovarian abscess  1  1/310 (0.32%)  0/309 (0.00%) 
Nervous system disorders     
Headache  1  1/310 (0.32%)  0/309 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  1/310 (0.32%)  0/309 (0.00%) 
Reproductive system and breast disorders     
Ovarian hyperstimulation syndrome  1  6/310 (1.94%)  10/309 (3.24%) 
Ovarian cyst ruptured  1  0/310 (0.00%)  1/309 (0.32%) 
Pelvic pain  1  1/310 (0.32%)  0/309 (0.00%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Menotropin Recombinant FSH
Affected / at Risk (%) Affected / at Risk (%)
Total   179/310 (57.74%)   218/309 (70.55%) 
Gastrointestinal disorders     
Abdominal distension  1  25/310 (8.06%)  35/309 (11.33%) 
Nausea  1  37/310 (11.94%)  40/309 (12.94%) 
Abdominal pain  1  21/310 (6.77%)  24/309 (7.77%) 
Constipation  1  22/310 (7.10%)  36/309 (11.65%) 
Injury, poisoning and procedural complications     
Procedural pain  1  71/310 (22.90%)  71/309 (22.98%) 
Nervous system disorders     
Headache  1  29/310 (9.35%)  22/309 (7.12%) 
Reproductive system and breast disorders     
Ovarian hyperstimulation syndrome  1  30/310 (9.68%)  66/309 (21.36%) 
Vaginal haemorrhage  1  21/310 (6.77%)  22/309 (7.12%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
Results Point of Contact
Name/Title: Clinical Development Support
Organization: Ferring Pharmaceuticals
Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02554279     History of Changes
Other Study ID Numbers: 000205
First Submitted: September 9, 2015
First Posted: September 18, 2015
Results First Submitted: January 25, 2018
Results First Posted: March 2, 2018
Last Update Posted: March 20, 2019