Back to resultsMenopur Mixed Protocol (COMBINE)
Primary Purpose
Infertility
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Bravelle
Menopur
Sponsored by
About this trial
This is an interventional treatment trial for Infertility focused on measuring Assisted Reproductive Technology
Eligibility Criteria
Main Inclusion Criteria:
- Infertile pre-menopausal female subjects
- Documented history of infertility (eg., unable to conceive for at least 1 year, or 6 months for women ≥36 years of age, or women with bilateral tubal occlusion or absence, or subjects who require donor sperm).
- Subject's male partner with semen analysis that was at least adequate for intracytoplasmic sperm injection (ICSI) within 6 months prior to the subjects beginning down-regulation with gonadotropin-releasing hormone (GnRH)-agonist. Partners with severe male factor requiring invasive or surgical sperm retrieval or donor sperm could have been used.
- Anti-mullerian hormone (AMH) > 1 ng/mL and < 3 ng/mL at screening.
- Eligible for in-vitro fertilisation (IVF) or ICSI treatment.
Main Exclusion Criteria:
- Oocyte donor or embryo recipient; gestational or surrogate carrier
- Previous IVF or assisted reproductive technology (ART) failure due to a poor response to gonadotropins. Poor response was defined as development of ≤ 2 mature follicles or history of 2 previous failed cycle cancellations prior to oocyte retrieval due to poor response.
- Inadequate number of oocytes, defined as fewer than 5 oocytes retrieved in previous ART attempts.
- Subject's male partners with obvious leukospermia (>2 million white blood cells [WBC]/mL) or signs of infection in semen sample within 2 months of the start of subject's pituitary down-regulation. If either of these conditions existed, the male was to be treated with antibiotics and retested prior to subject's pituitary down-regulation.
- Undergoing blastomere biopsy and other experimental ART procedures.
- Body mass index (BMI) of ≤18 and ≥32 kg/m^2
Sites / Locations
- Colorado Center for Reproductive Medicine
- Women's Medical Research Group
- Reproductive Biology Associates
- Fertility Center of Illinois
- The Advanced IVF Institute
- Shady Grove Fertility
- The Center for Assisted Reproduction
- Houston Fertility Institute
- Center of Reproductive Medicine
- Seattle Reproductive Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Menopur and Bravelle combination
Menopur alone
Arm Description
The initial daily dose consisted of 225 IU of gonadotropins, mixed in the same syringe and administered by subcutaneous (SC) injection for 5 days. The initial daily dose, based on the Investigator's judgment, consisted of either 150 IU of Menopur and 75 IU of Bravelle or 150 IU of Bravelle and 75 IU of Menopur. Dosing adjustments were allowed as of day 6. Dose could vary between 150-450 IU daily and was always to include at least 75 IU of Menopur and 75 IU of Bravelle. Treatment could not continue beyond day 20.
The initial daily dose consisted of 225 IU of Menopur administered by subcutaneous (SC) injection for 5 days. Dosing adjustments were allowed as of day 6. Dose could vary between 150-450 IU daily and treatment could not continue beyond day 20.
Outcomes
Primary Outcome Measures
Fertilization Rate
The fertilization rate was defined for each participant and calculated as the number of 2 pronuclei (fertilized) (2PN) oocytes divided by the total number of oocytes retrieved multiplied by 100.
Secondary Outcome Measures
Summary of the Subject Comprehension Questionnaire (SCQ) on Day 1
Subject comprehension questionnaires were completed on Day 1 only by participants assigned to the Menopur and Bravelle treatment arm. On Day 1, the participant read the Mixing Instructions Guide on how to mix and administer the medications at home. The participant was given enough time to read and understand the instructions and ask any questions. The participant then completed the SCQ which consists of 7 questions with YES/NO answers, to self-gauge their understanding of drug administration procedures. Reported data represent the number of participants who answered the question YES. Gonadotropins are referred to as investigational medicinal product (IMP).
Summary of the Subject Comprehension Questionnaire (SCQ) on Day 6
Subject comprehension questionnaires were repeated on Day 6 after 5 days of combination therapy by participants assigned to the Menopur and Bravelle treatment arm. The SCQ consists of 7 questions with YES/NO answers to self-gauge participants' understanding of drug administration procedures. Reported data represent the number of participants who answered the question YES. Gonadotropins are referred to as investigational medicinal product (IMP).
Summary of Assessor Questionnaire on Day 1
Participants assigned to the Menopur and Bravelle treatment arm read the Mixing Instructions Guide on how to mix and administer the medications at home. Participants were given enough time to read and understand the instructions and ask any questions. After completing the SCQ, participants prepared and self-administered her assigned first daily dose in the presence of the study coordinator or designee assessor. The assessor then completed a 7 question questionnaire with YES or NO answers to document their assessment of participant understanding of drug administration procedures. Reported data represent the number of participants for whom the assessor answered the question YES.
Gonadotropins are referred to as investigational medicinal product (IMP).
Summary of Assessor Questionnaire on Day 6
Participants assigned to the Menopur and Bravelle treatment arm prepared and self-administered her daily dose on Day 6 in the presence of the study coordinator or designee assessor. The assessor then completed a 7 question questionnaire with YES or NO answers to document their assessment of participant understanding of drug administration procedures. Reported data represent the number of participants for whom the assessor answered the question YES.
Gonadotropins are referred to as investigational medicinal product (IMP).
Participants With Treatment Emergent Adverse Events (TEAEs), Including Ovarian Hyperstimulation Syndrome (OHSS)
A treatment-emergent AE was any AE occurring after start of investigational medicinal product (IMP) and within the time of residual drug effect, or a pretreatment AE or pre-existing medical condition that worsened in intensity after start of IMP and within the time of residual drug effect. The time of residual drug effect was the estimated period of time after the last dose of the IMP, where the effect of the product was still considered to be present based on pharmacokinetic, pharmacodynamic, or other IMP characteristics.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01417195
Brief Title
Menopur Mixed Protocol
Acronym
COMBINE
Official Title
A Multicenter, Randomized, Open-label, Parallel-group Study Comparing the Combination of Menopur® and Bravelle® With Menopur® Alone in Subjects Undergoing Assisted Reproductive Technology (ART)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ferring Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objective of this study was to compare the fertilization rate between the combination of Menopur and Bravelle mixed in the same syringe and Menopur alone, both administered subcutaneously (SC), in subjects undergoing Assisted Reproductive Technology (ART). Additionally the study assessed subjects' ability to mix and store the combination of Menopur and Bravelle and to assess safety of the Menopur and Bravelle combination.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility
Keywords
Assisted Reproductive Technology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
122 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Menopur and Bravelle combination
Arm Type
Experimental
Arm Description
The initial daily dose consisted of 225 IU of gonadotropins, mixed in the same syringe and administered by subcutaneous (SC) injection for 5 days. The initial daily dose, based on the Investigator's judgment, consisted of either 150 IU of Menopur and 75 IU of Bravelle or 150 IU of Bravelle and 75 IU of Menopur. Dosing adjustments were allowed as of day 6. Dose could vary between 150-450 IU daily and was always to include at least 75 IU of Menopur and 75 IU of Bravelle. Treatment could not continue beyond day 20.
Arm Title
Menopur alone
Arm Type
Active Comparator
Arm Description
The initial daily dose consisted of 225 IU of Menopur administered by subcutaneous (SC) injection for 5 days. Dosing adjustments were allowed as of day 6. Dose could vary between 150-450 IU daily and treatment could not continue beyond day 20.
Intervention Type
Drug
Intervention Name(s)
Bravelle
Other Intervention Name(s)
Bravelle®, Urofollitropin, purified form of follicle-stimulating hormone (FSH)
Intervention Type
Drug
Intervention Name(s)
Menopur
Other Intervention Name(s)
Menopur®, Menotropin, HP-hMG, highly purified menotrophin
Primary Outcome Measure Information:
Title
Fertilization Rate
Description
The fertilization rate was defined for each participant and calculated as the number of 2 pronuclei (fertilized) (2PN) oocytes divided by the total number of oocytes retrieved multiplied by 100.
Time Frame
approximately day 13 (16-20 hours post insemination by in vitro fertilization (IVF) insemination or intracytoplasmic sperm injection (ICSI))
Secondary Outcome Measure Information:
Title
Summary of the Subject Comprehension Questionnaire (SCQ) on Day 1
Description
Subject comprehension questionnaires were completed on Day 1 only by participants assigned to the Menopur and Bravelle treatment arm. On Day 1, the participant read the Mixing Instructions Guide on how to mix and administer the medications at home. The participant was given enough time to read and understand the instructions and ask any questions. The participant then completed the SCQ which consists of 7 questions with YES/NO answers, to self-gauge their understanding of drug administration procedures. Reported data represent the number of participants who answered the question YES. Gonadotropins are referred to as investigational medicinal product (IMP).
Time Frame
Day 1
Title
Summary of the Subject Comprehension Questionnaire (SCQ) on Day 6
Description
Subject comprehension questionnaires were repeated on Day 6 after 5 days of combination therapy by participants assigned to the Menopur and Bravelle treatment arm. The SCQ consists of 7 questions with YES/NO answers to self-gauge participants' understanding of drug administration procedures. Reported data represent the number of participants who answered the question YES. Gonadotropins are referred to as investigational medicinal product (IMP).
Time Frame
Day 6
Title
Summary of Assessor Questionnaire on Day 1
Description
Participants assigned to the Menopur and Bravelle treatment arm read the Mixing Instructions Guide on how to mix and administer the medications at home. Participants were given enough time to read and understand the instructions and ask any questions. After completing the SCQ, participants prepared and self-administered her assigned first daily dose in the presence of the study coordinator or designee assessor. The assessor then completed a 7 question questionnaire with YES or NO answers to document their assessment of participant understanding of drug administration procedures. Reported data represent the number of participants for whom the assessor answered the question YES.
Gonadotropins are referred to as investigational medicinal product (IMP).
Time Frame
Day 1
Title
Summary of Assessor Questionnaire on Day 6
Description
Participants assigned to the Menopur and Bravelle treatment arm prepared and self-administered her daily dose on Day 6 in the presence of the study coordinator or designee assessor. The assessor then completed a 7 question questionnaire with YES or NO answers to document their assessment of participant understanding of drug administration procedures. Reported data represent the number of participants for whom the assessor answered the question YES.
Gonadotropins are referred to as investigational medicinal product (IMP).
Time Frame
Day 6
Title
Participants With Treatment Emergent Adverse Events (TEAEs), Including Ovarian Hyperstimulation Syndrome (OHSS)
Description
A treatment-emergent AE was any AE occurring after start of investigational medicinal product (IMP) and within the time of residual drug effect, or a pretreatment AE or pre-existing medical condition that worsened in intensity after start of IMP and within the time of residual drug effect. The time of residual drug effect was the estimated period of time after the last dose of the IMP, where the effect of the product was still considered to be present based on pharmacokinetic, pharmacodynamic, or other IMP characteristics.
Time Frame
Day 1 up to Day 20
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
42 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria:
Infertile pre-menopausal female subjects
Documented history of infertility (eg., unable to conceive for at least 1 year, or 6 months for women ≥36 years of age, or women with bilateral tubal occlusion or absence, or subjects who require donor sperm).
Subject's male partner with semen analysis that was at least adequate for intracytoplasmic sperm injection (ICSI) within 6 months prior to the subjects beginning down-regulation with gonadotropin-releasing hormone (GnRH)-agonist. Partners with severe male factor requiring invasive or surgical sperm retrieval or donor sperm could have been used.
Anti-mullerian hormone (AMH) > 1 ng/mL and < 3 ng/mL at screening.
Eligible for in-vitro fertilisation (IVF) or ICSI treatment.
Main Exclusion Criteria:
Oocyte donor or embryo recipient; gestational or surrogate carrier
Previous IVF or assisted reproductive technology (ART) failure due to a poor response to gonadotropins. Poor response was defined as development of ≤ 2 mature follicles or history of 2 previous failed cycle cancellations prior to oocyte retrieval due to poor response.
Inadequate number of oocytes, defined as fewer than 5 oocytes retrieved in previous ART attempts.
Subject's male partners with obvious leukospermia (>2 million white blood cells [WBC]/mL) or signs of infection in semen sample within 2 months of the start of subject's pituitary down-regulation. If either of these conditions existed, the male was to be treated with antibiotics and retested prior to subject's pituitary down-regulation.
Undergoing blastomere biopsy and other experimental ART procedures.
Body mass index (BMI) of ≤18 and ≥32 kg/m^2
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Development Support
Organizational Affiliation
Ferring Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Colorado Center for Reproductive Medicine
City
Lone Tree
State/Province
Colorado
Country
United States
Facility Name
Women's Medical Research Group
City
Clearwater
State/Province
Florida
Country
United States
Facility Name
Reproductive Biology Associates
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Fertility Center of Illinois
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
The Advanced IVF Institute
City
Naperville
State/Province
Illinois
Country
United States
Facility Name
Shady Grove Fertility
City
Rockville
State/Province
Maryland
Country
United States
Facility Name
The Center for Assisted Reproduction
City
Bedford
State/Province
Texas
Country
United States
Facility Name
Houston Fertility Institute
City
Houston
State/Province
Texas
Country
United States
Facility Name
Center of Reproductive Medicine
City
Webster
State/Province
Texas
Country
United States
Facility Name
Seattle Reproductive Medicine
City
Seattle
State/Province
Washington
Country
United States
12. IPD Sharing Statement
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Menopur Mixed Protocol
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