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Trial to Assess the Clinical Efficacy and Safety of MSJ-0011 in Inducing Ovulation in Anovulatory or Oligo-ovulatory Japanese Women

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ClinicalTrials.gov Identifier: NCT01653743
Recruitment Status : Completed
First Posted : July 31, 2012
Results First Posted : January 7, 2016
Last Update Posted : January 7, 2016
Sponsor:
Collaborator:
Merck Serono Co., Ltd., Japan
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Anovulation
Oligo-ovulation
Hypothalamic-pituitary Dysfunction
Polycystic Ovarian Syndrome
Interventions Drug: MSJ-0011
Drug: urinary hCG (u-hCG)
Drug: Follitropin alpha
Enrollment 81
Recruitment Details  
Pre-assignment Details  
Arm/Group Title MSJ-0011 u-hCG
Hide Arm/Group Description Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL). Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
Period Title: Overall Study
Started 54 27
Completed 50 27
Not Completed 4 0
Reason Not Completed
Withdrawal by Subject             1             0
Investigator discretion             3             0
Arm/Group Title MSJ-0011 Urinary Human Chorionic Gonadotropin (u-hCG) Total
Hide Arm/Group Description Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL). Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL. Total of all reporting groups
Overall Number of Baseline Participants 54 27 81
Hide Baseline Analysis Population Description
Safety population included all the subjects who received investigational medicinal product ([IMP]; MSJ-0011 or u-hCG)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 54 participants 27 participants 81 participants
32.61  (3.303) 30.67  (3.603) 31.96  (3.506)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 54 participants 27 participants 81 participants
Female
54
 100.0%
27
 100.0%
81
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Percentage of Subjects With Ovulation Mid-luteal Serum Progesterone (P4) Level of Greater Than or Equal (>=) 5 Nanogram Per Milliliter (ng/mL) or Clinical Pregnancy
Hide Description Ovulation was defined as mid-luteal serum progesterone level of >= 5 ng/mL or clinical pregnancy. Clinical pregnancy was defined as the presence of at least a fetal sac on transvaginal ultrasound (TVUS).
Time Frame Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The modified intent to treat (Mod ITT) population was defined as all subjects randomized to IMP (MSJ-0011 or u-hCG) and who completed the primary efficacy assessment.
Arm/Group Title MSJ-0011 u-hCG
Hide Arm/Group Description:
Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).
Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
Overall Number of Participants Analyzed 54 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
100
(93.4 to 100)
100
(87.2 to 100)
2.Secondary Outcome
Title Percentage of Subjects With Ovulation Mid-Luteal Serum Progesterone (P4) Level of Greater Than or Equal (>=) 9.4 Nanogram Per Milliliter (ng/mL) or Clinical Pregnancy
Hide Description Ovulation was defined as mid-luteal serum progesterone level of >= 9.4 ng/mL or clinical pregnancy. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS.
Time Frame Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The Mod ITT population was defined as all subjects randomized to IMP (MSJ-0011 or u-hCG) and who completed the primary efficacy assessment.
Arm/Group Title MSJ-0011 u-hCG
Hide Arm/Group Description:
Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).
Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
Overall Number of Participants Analyzed 54 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
96.3
(87.3 to 99.5)
88.9
(70.8 to 97.6)
3.Secondary Outcome
Title Mid-luteal Endometrial Thickness
Hide Description Endometrial thickness was measured using TVUS.
Time Frame Day 5 to 7 post hCG treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The Mod ITT population was defined as all subjects randomized to IMP (MSJ-0011 or u-hCG) and who completed the primary efficacy assessment.
Arm/Group Title MSJ-0011 u-hCG
Hide Arm/Group Description:
Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).
Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
Overall Number of Participants Analyzed 54 27
Mean (Standard Deviation)
Unit of Measure: millimeter
11.6  (2.64) 12.4  (2.58)
4.Secondary Outcome
Title Percentage of Participants With Biochemical Pregnancy
Hide Description Percentage of subjects with biochemical pregnancy was assessed. Biochemical pregnancy was defined as any miscarriage without any evidence of a fetal sac on TVUS on the Day 35 to 42 post hCG treatment, but with a positive serum β-hCG pregnancy test on Day 15 to 20 post hCG treatment (Beta-hCG level greater than [>] 10 IU/Liter)
Time Frame Day 35 to 42 post hCG treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The Mod ITT population was defined as all subjects randomized to IMP (MSJ-0011 or u-hCG) and who completed the primary efficacy assessment.
Arm/Group Title MSJ-0011 u-hCG
Hide Arm/Group Description:
Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).
Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
Overall Number of Participants Analyzed 54 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
3.7
(0.5 to 12.7)
3.7
(0.1 to 19.0)
5.Secondary Outcome
Title Percentage of Participants With Clinical Pregnancy
Hide Description Percentage of subjects with clinical pregnancy was assessed. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS.
Time Frame Day 35 to 42 post hCG treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The Mod ITT population was defined as all subjects randomized to IMP (MSJ-0011 or u-hCG) and who completed the primary efficacy assessment.
Arm/Group Title MSJ-0011 u-hCG
Hide Arm/Group Description:
Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).
Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
Overall Number of Participants Analyzed 54 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
29.6
(18.0 to 43.6)
33.3
(16.5 to 54.0)
Time Frame From signing of the informed consent document until Day 28-31 (for subjects who had a negative serum β-hCG pregnancy test on Day 15-20), or up to the Day 35-42 post hCG treatment (for subjects who have a positive serum β-hCG pregnancy test on Day 15-20).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title MSJ-0011 u-hCG
Hide Arm/Group Description Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL). Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
All-Cause Mortality
MSJ-0011 u-hCG
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
MSJ-0011 u-hCG
Affected / at Risk (%) Affected / at Risk (%)
Total   1/54 (1.85%)   0/27 (0.00%) 
Reproductive system and breast disorders     
Ovarian hyperstimulation syndrome * 1  1/54 (1.85%)  0/27 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
MSJ-0011 u-hCG
Affected / at Risk (%) Affected / at Risk (%)
Total   32/54 (59.26%)   11/27 (40.74%) 
Gastrointestinal disorders     
Abdominal distension * 1  0/54 (0.00%)  1/27 (3.70%) 
Abdominal pain * 1  2/54 (3.70%)  0/27 (0.00%) 
Abdominal pain upper * 1  1/54 (1.85%)  0/27 (0.00%) 
Ascites * 1  1/54 (1.85%)  0/27 (0.00%) 
Constipation * 1  2/54 (3.70%)  0/27 (0.00%) 
Diarrhoea * 1  1/54 (1.85%)  0/27 (0.00%) 
Nausea * 1  1/54 (1.85%)  0/27 (0.00%) 
Vomiting * 1  1/54 (1.85%)  0/27 (0.00%) 
General disorders     
Injection site bruising * 1  1/54 (1.85%)  0/27 (0.00%) 
Injection site erythema * 1  5/54 (9.26%)  2/27 (7.41%) 
Injection site pain * 1  2/54 (3.70%)  3/27 (11.11%) 
Injection site swelling * 1  1/54 (1.85%)  0/27 (0.00%) 
Infections and infestations     
Acute tonsillitis * 1  1/54 (1.85%)  0/27 (0.00%) 
Cystitis * 1  4/54 (7.41%)  0/27 (0.00%) 
Nasopharyngitis * 1  4/54 (7.41%)  1/27 (3.70%) 
Nervous system disorders     
Dizziness * 1  1/54 (1.85%)  0/27 (0.00%) 
Headache * 1  1/54 (1.85%)  0/27 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Haemorrhage in pregnancy * 1  1/54 (1.85%)  0/27 (0.00%) 
Reproductive system and breast disorders     
Dysmenorrhoea * 1  1/54 (1.85%)  0/27 (0.00%) 
Genital haemorrhage * 1  1/54 (1.85%)  0/27 (0.00%) 
Haemorrhagic ovarian cyst * 1  1/54 (1.85%)  0/27 (0.00%) 
Ovarian cyst * 1  6/54 (11.11%)  3/27 (11.11%) 
Ovarian enlargement * 1  1/54 (1.85%)  0/27 (0.00%) 
Ovarian hyperstimulation syndrome * 1  7/54 (12.96%)  4/27 (14.81%) 
Uterine haemorrhage * 1  1/54 (1.85%)  0/27 (0.00%) 
Skin and subcutaneous tissue disorders     
Drug eruption * 1  1/54 (1.85%)  0/27 (0.00%) 
Eczema * 1  1/54 (1.85%)  0/27 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.1
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.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Merck KGaA Communication Center
Organization: Merck KGaA
Phone: +49-6151-72-5200
EMail: service@merckgroup.com
Layout table for additonal information
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT01653743     History of Changes
Other Study ID Numbers: EMR701173_002
First Submitted: July 20, 2012
First Posted: July 31, 2012
Results First Submitted: December 1, 2015
Results First Posted: January 7, 2016
Last Update Posted: January 7, 2016