MENOPUR® Versus FOLLISTIM®

• Sponsor: Ferring Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00802360
• Collaborator: (none)
• Enrollment: 173
• Locations: 7
• Arms: 4
• Duration (Months): 13
• Patients Per Site: 24.7
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

To compare the efficacy and safety of highly purified menotropin (Menopur®) with that of follitropin beta (FOLLISTIM®) in patients who are undergoing gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles

Condition or Disease	Intervention/Treatment	Phase
Infertility	Drug: Menotropin; Drug: Progestrone vaginal insert; Drug: follitropin beta; Drug: Progesterone in oil; Drug: Ganirelix	Phase 4

Detailed Description

This multicenter, randomized, open-label exploratory study will be performed in approximately 200 healthy females undergoing in vitro fertilization (IVF). Each study center will follow its study center standard practice for in vitro fertilization (IVF) within the study parameters as noted in this protocol. The study centers will use marketed products purchased from Schraft's Pharmacy for all phases of the study (down-regulation, stimulation, ovulation induction, and luteal support). Subjects will be randomly assigned prior to the start of stimulation to highly purified menotropin (Menopur®) or follitropin beta (Follistim Pen®) for stimulation and progesterone vaginal insert (Endometrin®) or progesterone in oil for luteal support. Subjects will return to the study center for regular scheduled clinic visits as required per in vitro fertilization (IVF) protocol at the site and at specified time periods during the cycle for estradiol (E2), progesterone (P4) and human chorionic gonadotropin (hCG) tests, and first serum pregnancy test. All subjects will be required to complete a final study visit at completion of luteal support or negative serum pregnancy test following embryo transfer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 173 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Randomized, Open-Label Evaluation of MENOPUR® Versus FOLLISTIM® in GnRH Antagonist Cycles
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Menopur/Endometrin Highly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progestrone vaginal insert (Endometrin®) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Drug: Menotropin; 225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days until human chorionic gonadotropin (hCG) criteria are met.; Other Names: highly purified menotropins Menopur® hMG ; Drug: Progestrone vaginal insert; 100 mg progesterone vaginal insert 2 or 3 times daily (BID or TID) (start on the day after oocyte retrieval) until 10 weeks gestation or confirmation of negative pregnancy test.; Other Names: progesterone Endometrin® ; Drug: Ganirelix; Ganirelix acetate 250 µg as a daily subcutaneous injection starting on day 6 and continuing until hCG criteria were met.; Other Names: ganirelix acetate GnRH antagonist
Experimental: Menopur/Progesterone in Oil Highly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in Oil injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Drug: Menotropin; 225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days until human chorionic gonadotropin (hCG) criteria are met.; Other Names: highly purified menotropins Menopur® hMG ; Drug: Progesterone in oil; 50 mg by intramuscular injection once per day, starting on the day after oocyte retrieval until 10 weeks gestation or confirmation of negative pregnancy test.; Drug: Ganirelix; Ganirelix acetate 250 µg as a daily subcutaneous injection starting on day 6 and continuing until hCG criteria were met.; Other Names: ganirelix acetate GnRH antagonist
Active Comparator: Follistim/Endometrin Follitropin beta (Follistim®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progestrone vaginal insert (Endometrin®) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Drug: Progestrone vaginal insert; 100 mg progesterone vaginal insert 2 or 3 times daily (BID or TID) (start on the day after oocyte retrieval) until 10 weeks gestation or confirmation of negative pregnancy test.; Other Names: progesterone Endometrin® ; Drug: follitropin beta; 225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days until human chorionic gonadotropin (hCG) criteria are met.; Other Names: Follistim Pen® Follistim® ; Drug: Ganirelix; Ganirelix acetate 250 µg as a daily subcutaneous injection starting on day 6 and continuing until hCG criteria were met.; Other Names: ganirelix acetate GnRH antagonist
Active Comparator: Follistim/Progesterone in Oil Follitropin beta (Follistim®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in Oil injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Drug: follitropin beta; 225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days until human chorionic gonadotropin (hCG) criteria are met.; Other Names: Follistim Pen® Follistim® ; Drug: Progesterone in oil; 50 mg by intramuscular injection once per day, starting on the day after oocyte retrieval until 10 weeks gestation or confirmation of negative pregnancy test.; Drug: Ganirelix; Ganirelix acetate 250 µg as a daily subcutaneous injection starting on day 6 and continuing until hCG criteria were met.; Other Names: ganirelix acetate GnRH antagonist

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Ongoing Pregnancy at Week 8 [Week 8 (Week 6 of gestation)]

   The ongoing pregnancy was defined as a positive fetal heart movement (motion) at approximately six weeks of gestation and confirmed in a follow-up pregnancy ultrasound.

Secondary Outcome Measures

1. Number of Follicles Observed at Day 15 [Day 15]

   The mean number of follicles observed in both ovaries at the last transvaginal ultrasound in the stimulation phase.

2. Number of Oocytes Retrieved at Day 18 [Approximately Day 18]

   The mean number of oocytes retrieved within 34-36 hours of human chorionic gonadotropin (hCG) administration.

3. Proportion of Oocytes Fertilized of the Total Number of Oocytes Retrieved [Approximately Day 19]

   The proportion of the number of oocytes inseminated (fertilized) of the total number of oocytes retrieved.

4. Number of Embryos Transferred at Three Stages of Development [Approximately Day 24]

   The number of embryos, morula and blastocytes transferred to the study participant on either day 3 or day 5 following fertilization.

5. Number of Embryos Frozen at Day 24 [Approximately Day 24]

   The number of embryos that were not transferred but instead were frozen for future use.

6. Participants With Cycle Cancellation Following One In Vitro Fertilization (IVF) Treatment Cycle [Day 1 to Day 24]

   A count of participants whose discontinuation was clearly documented on the study completion/termination form as 1) due to cycle cancelled or 2) cycle cancellation for risk of ovarian hyperstimulation syndrome (OHSS).

7. Participants With Biochemical Pregnancy at Day 38 [approximately day 38 (Day 14 post embryo transfer)]

   Biochemical pregnancy is a positive β-hCG pregnancy test 12-14 days post embryo transfer.

8. Participants With Clinical Pregnancy at Week 7 [approximately week 7]

   Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.

9. Participants With Adverse Events (AEs), Including Ovarian Hyperstimulation Syndrome (OHSS) [Day 1 - week 12]

   Number of participants with adverse events (AEs) that started after first treatment. Severity used a three point scale: mild=awareness of signs/symptoms, but no disruption of usual activity moderate=event sufficient to affect usual activity (disturbing) severe=event causes inability to work or perform usual activities (unacceptable) Relatedness to study treatment used a four point scale: unrelated, unlikely, possible, probable. Seriousness refers to death, hospitalization, a life-threatening experience, persistent or significant disability/incapacity, or congenital anomaly.

10. Number of Live Births [Approximately 10 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 42 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Pre-menopausal females between the ages of 18 and 42 years

2. Body mass index (BMI) of 18-34

3. Early follicular phase (day 2-4) Follicle stimulating hormone (FSH) <15 IU/L and Estradiol (E2) within normal limits

4. Documented history of infertility (e.g., unable to conceive for at least one year, or for 6 months for women >38 years of age, or bilateral tubal occlusion or absence, or male factor but excluding severe male factor requiring invasive or surgical sperm retrieval. Donor sperm may be used.)

5. Transvaginal ultrasound at screening consistent with findings adequate for assisted reproductive technology (ART) with respect to uterus and adnexa

6. Signed informed consent

Exclusion Criteria:

1. Gestational or surrogate carrier, donor oocyte

2. Presence of any clinically relevant systemic disease (e.g., insulin-dependent diabetes mellitus, uterine cancer)

3. Surgical or medical condition which, in the judgment of the Investigator or Sponsor, may interfere with absorption, distribution, metabolism, or excretion of the drugs to be used

4. Previous In vitro fertilization (IVF) or Assisted reproductive technology (ART) failure due to a poor response to gonadotropins. Poor response is defined as development of 2 mature follicles or history of >2 previous failed in vitro fertilization (IVF) cycles.

5. History of recurrent pregnancy loss (>2).

6. Presence of abnormal uterine bleeding of undetermined origin

7. Current or recent substance abuse, including alcohol or smoking >10 cigarettes per day

8. Refusal or inability to comply with the requirements of the Protocol for any reason, including scheduled clinic visits and laboratory tests

9. Participation in any experimental drug study within 30 days prior to Screening

10. Severe male factor requiring invasive or surgical sperm retrieval (e.g., microsurgical epididymal sperm aspiration [MESA], testicular sperm extraction [TESE])

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Huntington Reproductive Center	Pasadena	California	United States	91105
2	San Diego Fertility Center	San Diego	California	United States	92130
3	Conceptions Reproductive Associates of Colorado	Littleton	Colorado	United States	80129
4	Women's Medical Research Group, LLC	Clearwater	Florida	United States	33759
5	The Advanced IVF Institute; Charles E. Miller, MD & Associates	Naperville	Illinois	United States	60540
6	A Woman's Center for Reproductive Medicine	Baton Rouge	Louisiana	United States	70815
7	Center for Assisted Reproduction	Bedford	Texas	United States	76022

Sponsors and Collaborators

• Ferring Pharmaceuticals

Investigators

• Study Director: Clinical Development Support, Ferring Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00802360
• Other Study ID Numbers: 2008-04
• First Posted: Dec 4, 2008
• Last Update Posted: Nov 2, 2011
• Last Verified: Oct 1, 2011

• Keywords provided by Ferring Pharmaceuticals: Healthy, pre-menopausal women, age 18-42 with a history of infertility and requiring IVF
• Additional relevant MeSH terms: Infertility; Menotropins; Progesterone; Follicle Stimulating Hormone; Ganirelix

Study Results

Participant Flow

Recruitment Details	One hundred ninety one (191) participants were screened from 6 study centers in the US; 173 of these participants were eligible for randomization. Six subjects did not receive their respected treatment and two subjects withdrew consent, 165 subjects were included in the statistical analyses

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description	Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Period Title: Overall Study
STARTED	42	42	42	39
COMPLETED	18	16	17	17
NOT COMPLETED	24	26	25	22

Baseline Characteristics

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil	Total
Arm/Group Description	Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Total of all reporting groups
Overall Participants	42	42	42	39	165
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.5 (4.1)	33.2 (4.8)	34.0 (4.3)	33.9 (4.3)	33.9 (7.4)
Sex: Female, Male (Count of Participants)
Female	42 100%	42 100%	42 100%	39 100%	165 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	32 76.2%	35 83.3%	31 73.8%	32 82.1%	130 78.8%
African American	5 11.9%	1 2.4%	2 4.8%	2 5.1%	10 6.1%
Asian	4 9.5%	2 4.8%	6 14.3%	2 5.1%	14 8.5%
Hispanic	1 2.4%	4 9.5%	3 7.1%	1 2.6%	9 5.5%
Other	0 0%	0 0%	0 0%	2 5.1%	2 1.2%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	24.6 (4.1)	23.8 (3.0)	25.0 (3.3)	25.6 (4.5)	24.6 (3.8)
Follicle-stimulating hormone level (mIU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mIU/mL]	7.4 (2.3)	7.1 (2.2)	6.9 (2.0)	6.9 (2.9)	7.3 (2.3)

Outcome Measures

1. Secondary Outcome

Title	Number of Follicles Observed at Day 15
Description	The mean number of follicles observed in both ovaries at the last transvaginal ultrasound in the stimulation phase.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication

Arm/Group Title	Menopur	Follistim
Arm/Group Description	Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.
Measure Participants	84	81
Mean (Standard Deviation) [follicles]	15.6 (8.6)	16.2 (8.4)

2. Secondary Outcome

Title	Number of Oocytes Retrieved at Day 18
Description	The mean number of oocytes retrieved within 34-36 hours of human chorionic gonadotropin (hCG) administration.
Time Frame	Approximately Day 18

Outcome Measure Data

Analysis Population Description

Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication and had oocytes retrieved.

Arm/Group Title	Menopur	Follistim
Arm/Group Description	Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.
Measure Participants	79	74
Mean (Standard Deviation) [oocytes]	11.5 (6.3)	13.8 (7.9)

3. Secondary Outcome

Title	Proportion of Oocytes Fertilized of the Total Number of Oocytes Retrieved
Description	The proportion of the number of oocytes inseminated (fertilized) of the total number of oocytes retrieved.
Time Frame	Approximately Day 19

Outcome Measure Data

Analysis Population Description

Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication and had oocytes retrieved.

Arm/Group Title	Menopur	Follistim
Arm/Group Description	Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.
Measure Participants	79	73
Mean (Standard Deviation) [proportion of oocytes retrieved]	0.3 (0.4)	0.3 (0.4)

4. Secondary Outcome

Title	Number of Embryos Transferred at Three Stages of Development
Description	The number of embryos, morula and blastocytes transferred to the study participant on either day 3 or day 5 following fertilization.
Time Frame	Approximately Day 24

Outcome Measure Data

Analysis Population Description

Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication and had embryos transferred.

Arm/Group Title	Menopur	Follistim
Arm/Group Description	Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.
Measure Participants	78	69
Number of Embryos transferred	2.1 (0.7)	2.4 (0.7)
Number of Morula transferred	0.0 (0.1)	0.1 (0.4)
Number of Blastocytes transferred	0.9 (1)	0.9 (1)

5. Secondary Outcome

Title	Number of Embryos Frozen at Day 24
Description	The number of embryos that were not transferred but instead were frozen for future use.
Time Frame	Approximately Day 24

Outcome Measure Data

Analysis Population Description

Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication and had oocytes fertilized

Arm/Group Title	Menopur	Follistim
Arm/Group Description	Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.
Measure Participants	78	69
Mean (Standard Deviation) [embryos]	1.9 (2.9)	1.6 (2.5)

6. Secondary Outcome

Title	Participants With Cycle Cancellation Following One In Vitro Fertilization (IVF) Treatment Cycle
Description	A count of participants whose discontinuation was clearly documented on the study completion/termination form as 1) due to cycle cancelled or 2) cycle cancellation for risk of ovarian hyperstimulation syndrome (OHSS).
Time Frame	Day 1 to Day 24

Outcome Measure Data

Analysis Population Description

Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description	Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Measure Participants	42	42	42	39
Number [participants]	0 0%	1 2.4%	1 2.4%	2 5.1%

7. Primary Outcome

Title	Percentage of Participants With Ongoing Pregnancy at Week 8
Description	The ongoing pregnancy was defined as a positive fetal heart movement (motion) at approximately six weeks of gestation and confirmed in a follow-up pregnancy ultrasound.
Time Frame	Week 8 (Week 6 of gestation)

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description	Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Measure Participants	42	42	42	39
Number [percentage of participants]	45.2 107.6%	45.2 107.6%	42.9 102.1%	48.7 124.9%

8. Secondary Outcome

Title	Participants With Biochemical Pregnancy at Day 38
Description	Biochemical pregnancy is a positive β-hCG pregnancy test 12-14 days post embryo transfer.
Time Frame	approximately day 38 (Day 14 post embryo transfer)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication and had an embryo transfer

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description	Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Measure Participants	38	40	36	33
Number [participants]	21 50%	20 47.6%	22 52.4%	23 59%

9. Secondary Outcome

Title	Participants With Clinical Pregnancy at Week 7
Description	Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.
Time Frame	approximately week 7

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication and had an embryo transfer

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description	Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Measure Participants	38	40	36	33
Number [participants]	19 45.2%	19 45.2%	18 42.9%	20 51.3%

10. Secondary Outcome

Title	Participants With Adverse Events (AEs), Including Ovarian Hyperstimulation Syndrome (OHSS)
Description	Number of participants with adverse events (AEs) that started after first treatment. Severity used a three point scale: mild=awareness of signs/symptoms, but no disruption of usual activity moderate=event sufficient to affect usual activity (disturbing) severe=event causes inability to work or perform usual activities (unacceptable) Relatedness to study treatment used a four point scale: unrelated, unlikely, possible, probable. Seriousness refers to death, hospitalization, a life-threatening experience, persistent or significant disability/incapacity, or congenital anomaly.
Time Frame	Day 1 - week 12

Outcome Measure Data

Analysis Population Description

Safety population all randomized and treated participants. The safety population is identical intent-to- treat (ITT) population in this study

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description	Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Measure Participants	42	42	42	39
With at least one adverse event	20 47.6%	18 42.9%	18 42.9%	21 53.8%
Mild or moderate adverse event	20 47.6%	18 42.9%	18 42.9%	21 53.8%
Severe adverse event	1 2.4%	0 0%	2 4.8%	0 0%
Serious adverse event	0 0%	1 2.4%	1 2.4%	0 0%
Unrelated or unlikely adverse event	15 35.7%	13 31%	17 40.5%	14 35.9%
Possibly or probably related adverse event	10 23.8%	8 19%	7 16.7%	15 38.5%

11. Secondary Outcome

Title	Number of Live Births
Time Frame	Approximately 10 months

Outcome Measure Data

Analysis Population Description

Database was locked prior to all participants giving birth.

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description	Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Measure Participants	0	0	0	0

Adverse Events

Time Frame	Treatment-emergent adverse events were collected from Day 1 to Week 12.
Adverse Event Reporting Description	Multiple events in the same system organ class for a subject are only counted once for that system organ class.
Arm/Group Title	Menopur/Endometrin		Menopur/Progesterone in Oil		Follistim/Endometrin		Follistim/Progesterone in Oil
Arm/Group Description	Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.		Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.		Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.		Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
All Cause Mortality
	Menopur/Endometrin		Menopur/Progesterone in Oil		Follistim/Endometrin		Follistim/Progesterone in Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Menopur/Endometrin		Menopur/Progesterone in Oil		Follistim/Endometrin		Follistim/Progesterone in Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		1/42 (2.4%)		1/42 (2.4%)		0/39 (0%)
Gastrointestinal disorders
Hyperemesis gravidarum	0/42 (0%)		0/42 (0%)		1/42 (2.4%)		0/39 (0%)
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome with ascites	0/42 (0%)		1/42 (2.4%)		0/42 (0%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	Menopur/Endometrin		Menopur/Progesterone in Oil		Follistim/Endometrin		Follistim/Progesterone in Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/42 (47.6%)		18/42 (42.9%)		18/42 (42.9%)		21/39 (53.8%)
Gastrointestinal disorders
Abdominal distension	4/42 (9.5%)		6/42 (14.3%)		3/42 (7.1%)		5/39 (12.8%)
Abdominal pain lower	3/42 (7.1%)		0/42 (0%)		0/42 (0%)		0/39 (0%)
Abdominal pain upper	1/42 (2.4%)		0/42 (0%)		0/42 (0%)		2/39 (5.1%)
Nausea	3/42 (7.1%)		5/42 (11.9%)		3/42 (7.1%)		8/39 (20.5%)
Abdominal discomfort	1/42 (2.4%)		0/42 (0%)		0/42 (0%)		0/39 (0%)
Abdominal pain	0/42 (0%)		0/42 (0%)		2/42 (4.8%)		0/39 (0%)
Ascites	0/42 (0%)		0/42 (0%)		1/42 (2.4%)		0/39 (0%)
Constipation	1/42 (2.4%)		1/42 (2.4%)		2/42 (4.8%)		0/39 (0%)
Dyspepsia	0/42 (0%)		1/42 (2.4%)		0/42 (0%)		0/39 (0%)
Flatulence	1/42 (2.4%)		0/42 (0%)		0/42 (0%)		0/39 (0%)
Stomach discomfort	0/42 (0%)		0/42 (0%)		1/42 (2.4%)		0/39 (0%)
Vomiting	1/42 (2.4%)		2/42 (4.8%)		2/42 (4.8%)		1/39 (2.6%)
General disorders
Adverse drug reaction	0/42 (0%)		1/42 (2.4%)		0/42 (0%)		0/39 (0%)
Fatigue	0/42 (0%)		0/42 (0%)		0/42 (0%)		1/39 (2.6%)
Injection site discomfort	0/42 (0%)		0/42 (0%)		0/42 (0%)		1/39 (2.6%)
Injection site erythema	0/42 (0%)		0/42 (0%)		0/42 (0%)		1/39 (2.6%)
Injection site oedema	0/42 (0%)		1/42 (2.4%)		0/42 (0%)		0/39 (0%)
Injection site pruritus	0/42 (0%)		0/42 (0%)		0/42 (0%)		1/39 (2.6%)
Injection site rash	0/42 (0%)		0/42 (0%)		0/42 (0%)		1/39 (2.6%)
Irritability	1/42 (2.4%)		0/42 (0%)		0/42 (0%)		0/39 (0%)
Oedema peripheral	0/42 (0%)		0/42 (0%)		1/42 (2.4%)		0/39 (0%)
Immune system disorders
Drug hypersensitivity	0/42 (0%)		0/42 (0%)		1/42 (2.4%)		0/39 (0%)
Infections and infestations
Fungal infection	1/42 (2.4%)		0/42 (0%)		0/42 (0%)		1/39 (2.6%)
Nasopharyngitis	0/42 (0%)		0/42 (0%)		1/42 (2.4%)		1/39 (2.6%)
Urinary tract infection	0/42 (0%)		0/42 (0%)		1/42 (2.4%)		0/39 (0%)
Vulvovaginal mycotic infection	1/42 (2.4%)		2/42 (4.8%)		1/42 (2.4%)		1/39 (2.6%)
Injury, poisoning and procedural complications
Procedural pain	1/42 (2.4%)		3/42 (7.1%)		5/42 (11.9%)		2/39 (5.1%)
Incision site complication	0/42 (0%)		1/42 (2.4%)		0/42 (0%)		0/39 (0%)
Injection site anaesthesia	0/42 (0%)		0/42 (0%)		0/42 (0%)		1/39 (2.6%)
Procedural nausea	1/42 (2.4%)		1/42 (2.4%)		2/42 (4.8%)		0/39 (0%)
Investigations
Alanine aminotransferase increased	0/42 (0%)		0/42 (0%)		0/42 (0%)		1/39 (2.6%)
Metabolism and nutrition disorders
Decreased appetite	0/42 (0%)		1/42 (2.4%)		0/42 (0%)		0/39 (0%)
Musculoskeletal and connective tissue disorders
Back pain	2/42 (4.8%)		2/42 (4.8%)		0/42 (0%)		0/39 (0%)
Musculoskeletal pain	0/42 (0%)		0/42 (0%)		1/42 (2.4%)		0/39 (0%)
Myalgia	0/42 (0%)		0/42 (0%)		1/42 (2.4%)		0/39 (0%)
Nervous system disorders
Dizziness	1/42 (2.4%)		0/42 (0%)		1/42 (2.4%)		2/39 (5.1%)
Headache	1/42 (2.4%)		1/42 (2.4%)		2/42 (4.8%)		1/39 (2.6%)
Migraine	0/42 (0%)		0/42 (0%)		0/42 (0%)		1/39 (2.6%)
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	0/42 (0%)		1/42 (2.4%)		1/42 (2.4%)		0/39 (0%)
Psychiatric disorders
Depression	1/42 (2.4%)		0/42 (0%)		0/42 (0%)		0/39 (0%)
Insomnia	0/42 (0%)		1/42 (2.4%)		1/42 (2.4%)		0/39 (0%)
Renal and urinary disorders
Bladder pain	1/42 (2.4%)		0/42 (0%)		0/42 (0%)		0/39 (0%)
Reproductive system and breast disorders
Adnexa uteri pain	6/42 (14.3%)		7/42 (16.7%)		6/42 (14.3%)		9/39 (23.1%)
Ovarian hyperstimulation syndrome	3/42 (7.1%)		1/42 (2.4%)		1/42 (2.4%)		8/39 (20.5%)
Pelvic pain	0/42 (0%)		0/42 (0%)		0/42 (0%)		2/39 (5.1%)
Breast tenderness	2/42 (4.8%)		0/42 (0%)		0/42 (0%)		0/39 (0%)
Metrorrhagia	1/42 (2.4%)		0/42 (0%)		1/42 (2.4%)		1/39 (2.6%)
Pelvic discomfort	0/42 (0%)		1/42 (2.4%)		0/42 (0%)		0/39 (0%)
Uterine spasm	1/42 (2.4%)		1/42 (2.4%)		2/42 (4.8%)		1/39 (2.6%)
Vaginal discharge	0/42 (0%)		1/42 (2.4%)		0/42 (0%)		0/39 (0%)
Vaginal haemorrhage	2/42 (4.8%)		0/42 (0%)		2/42 (4.8%)		0/39 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/42 (2.4%)		0/42 (0%)		0/42 (0%)		0/39 (0%)
Dyspnoea	1/42 (2.4%)		0/42 (0%)		1/42 (2.4%)		0/39 (0%)
Nasal congestion	0/42 (0%)		0/42 (0%)		0/42 (0%)		1/39 (2.6%)
Pharyngolaryngeal pain	2/42 (4.8%)		0/42 (0%)		1/42 (2.4%)		1/39 (2.6%)
Sinus congestion	0/42 (0%)		0/42 (0%)		1/42 (2.4%)		0/39 (0%)
Skin and subcutaneous tissue disorders
Acne	1/42 (2.4%)		1/42 (2.4%)		0/42 (0%)		0/39 (0%)
Vascular disorders
Haematoma	0/42 (0%)		1/42 (2.4%)		0/42 (0%)		0/39 (0%)

Limitations/Caveats

This was an exploratory study that could be used as the basis for larger, adequately-powered studies. This limitation is the reason no statistical analyses are offered for study outcomes.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.