Menopur Mixed Protocol

Study Overview
=================
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.

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)

Conditions
-----------------
Infertility

Intervention / Treatment
-----------------
* Drug: Bravelle
* Drug: Menopur


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 42 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Menopur and Bravelle combination<br>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. | Drug: Bravelle<br> <br> * Other names: purified form of follicle-stimulating hormone (FSH);Drug: Menopur<br> <br> * Other names: highly purified menotrophin;|
| Active Comparator: Menopur alone<br>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. | Drug: Menopur<br> <br> * Other names: highly purified menotrophin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | approximately day 13 (16-20 hours post insemination by in vitro fertilization (IVF) insemination or intracytoplasmic sperm injection (ICSI)) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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). | 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). | 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). | 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. | Day 1 up to Day 20 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Assisted Reproductive Technology