InfertilityPhase 4COMBINENCT01417195
Menopur Mixed Protocol
A Phase 4 study testing Bravelle and Menopur in people with Infertility, run by Ferring Pharmaceuticals at 10 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 42 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Bravelle and Menopur
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- 10 sitesUnited States
- Study dates
- Jul 2011to Jan 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 42 years
- Women only
- No healthy volunteers
- Adult
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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Reproductive Biology Associates
Atlanta, Georgia
The Center for Assisted Reproduction
Bedford, Texas
Fertility Center of Illinois
Chicago, Illinois
Women's Medical Research Group
Clearwater, Florida
Houston Fertility Institute
Houston, Texas
Colorado Center for Reproductive Medicine
Lone Tree, Colorado
The Advanced IVF Institute
Naperville, Illinois
Shady Grove Fertility
Rockville, Maryland
Seattle Reproductive Medicine
Seattle, Washington
Center of Reproductive Medicine
Webster, Texas
About this study
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)
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.
- Conditions
- Infertility
- Being tested
- Bravelle, Menopur
- Keywords
- Assisted Reproductive Technology
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BravelleDrug
Also called Bravelle®, Urofollitropin, purified form of follicle-stimulating hormone (FSH)
MenopurDrug
Also called Menopur®, Menotropin, HP-hMG, highly purified menotrophin
| Study group | Role | What they receive |
|---|---|---|
| Menopur and Bravelle combination | Experimental | 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. Receives: Drug: Bravelle; Drug: Menopur |
| Menopur alone | Active comparator | 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. Receives: Drug: Menopur |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: approximately day 13 (16-20 hours post insemination by in vitro fertilization (IVF) insemination or intracytoplasmic sperm injection (ICSI))
Secondary outcomes (5)
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).
Measured: Day 1
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).
Measured: Day 6
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).
Measured: Day 1
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).
Measured: Day 6
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.
Measured: Day 1 up to Day 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2011 (estimated)
- Study startJul 2011
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ferring Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Development Support, Study director, Ferring Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01417195
- Sponsor's protocol ID
- FE999906 CS12
- Acronym
- COMBINE
- Status last verified
- May 2014
- First submitted
- 28 Jul 2011
- Last updated
- 16 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01417195
- Acronym / sponsor ID
- COMBINE / FE999906 CS12
- Conditions
- Infertility
- Keywords
- Assisted Reproductive Technology
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Ferring PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 16 Aug 2011 (estimated)
- Results
- Posted 24 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Menopur and Bravelle combination | Experimental | Drug: Bravelle, Drug: MenopurThe 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. |
| Menopur alone | Active comparator | Drug: MenopurThe 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. |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BravelleAlso: Bravelle®, Urofollitropin, purified form of follicle-stimulating hormone (FSH) | Drug | Menopur and Bravelle combination |
| MenopurAlso: Menopur®, Menotropin, HP-hMG, highly purified menotrophin | Drug | Menopur alone, Menopur and Bravelle combination |
Primary outcome
Fertilization Rate
Time frame: approximately day 13 (16-20 hours post insemination by in vitro fertilization (IVF) insemination or intracytoplasmic sperm injection (ICSI))
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.
5 secondary outcomes
Summary of the Subject Comprehension Questionnaire (SCQ) on Day 1
Time frame: Day 1
Summary of the Subject Comprehension Questionnaire (SCQ) on Day 6
Time frame: Day 6
Summary of Assessor Questionnaire on Day 1
Time frame: Day 1
Summary of Assessor Questionnaire on Day 6
Time frame: Day 6
Participants With Treatment Emergent Adverse Events (TEAEs), Including Ovarian Hyperstimulation Syndrome (OHSS)
Time frame: Day 1 up to Day 20
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Development Support study director
Ferring Pharmaceuticals
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bravelle and Menopur in people with Infertility, run by Ferring Pharmaceuticals at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fertilization Rate (time frame: approximately day 13 (16-20 hours post insemination by in vitro fertilization (IVF) insemination or intracytoplasmic sperm injection (ICSI))). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2014.