A Study of the Efficacy and Safety of Highly Purified Menotrophin Versus Recombinant Follitropin Alfa

• ClinicalTrials.gov Identifier: NCT00257556
• Recruitment Status: Completed
• First Posted: November 23, 2005
• Results First Posted: February 26, 2010
• Last Update Posted: February 26, 2010
• Sponsor: Ferring Pharmaceuticals
• Information provided by: Ferring Pharmaceuticals

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Infertility
• Interventions: Drug: Menotrophin; Drug: Follitropin alfa
• Enrollment: 80

Participant Flow

Recruitment Details
Pre-assignment Details	Ninety (90) participants were screened and 80 participants randomized.

Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
Period Title: Overall Study
Started	38	42
All Patients Treated Population	37 [1]	39 [2]
Completed	24	32
Not Completed	14	10
Reason Not Completed
Adverse Event	1	4
Physician Decision	6	0
Did not meet hCG criterion	3	0
other reason	4	6
[1] Also the safety population. One randomized patient did not receive study medication.; [2] Also the safety population. Three randomized patients did not receive study medication.

Baseline Characteristics

Arm/Group Title		Menotrophin	Follitropin Alfa	Total
Arm/Group Description		Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).	Total of all reporting groups
Overall Number of Baseline Participants		37	39	76
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	37 participants	39 participants	76 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	37 100.0%	39 100.0%	76 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	37 participants	39 participants	76 participants
		30.7 (3.45)	30.9 (2.67)	30.8 (3.06)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	37 participants	39 participants	76 participants
	Female	37 100.0%	39 100.0%	76 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Tobacco Use; Measure Type: Number; Unit of measure: Participants	Number Analyzed	37 participants	39 participants	76 participants
Smoker		4	8	12
Ex-smoker		8	5	13
Never Smoked		25	26	51
Body Mass Index [1]; Mean (Standard Deviation); Unit of measure: Kilograms/Meters squared
	Number Analyzed	37 participants	39 participants	76 participants
		24.02 (3.689)	23.81 (3.731)	23.91 (3.687)
		[1] Measure Description: Body mass index (BMI) is measure of body fat based on height and weight that applies to both adult men and women
Diastolic Blood Pressure; Mean (Standard Deviation); Unit of measure: Mm Hg
	Number Analyzed	37 participants	39 participants	76 participants
		74.1 (8.83)	73.8 (9.96)	74.0 (9.37)
Pulse; Mean (Standard Deviation); Unit of measure: Beats per minute
	Number Analyzed	37 participants	39 participants	76 participants
		75.7 (9.63)	74.5 (9.16)	75.1 (9.35)
Systolic Blood Pressure; Mean (Standard Deviation); Unit of measure: Mm Hg
	Number Analyzed	37 participants	39 participants	76 participants
		115.3 (12.50)	116.1 (14.55)	115.7 (13.51)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With an Ongoing Pregnancy
Description	Number of participants who met human chorionic gonadotrophin (hCG) criterion, received an embryo transfer, tested positive with a serum pregnancy test 11-14 days after embryo transfer and had an ongoing pregnancy (defined as positive fetal heart action) at ≥ 9 weeks after the first positive pregnancy test.
Time Frame	Approx week 13; 9 weeks or more after the 1st positive pregnancy test

Outcome Measure Data

Analysis Population Description

All patients treated population

Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description:	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
Overall Number of Participants Analyzed	37	39
Measure Type: Number; Unit of Measure: participants
	14	13

2. Primary Outcome

Title	Percentage of Participants With an Ongoing Pregnancy
Description	Percentage of participants who had an ongoing pregnancy ≥ 9 weeks after the first positive pregnancy test, as indicated by positive fetal heart action.
Time Frame	Approx week 13; 9 weeks or more after the first positive pregnancy test

Outcome Measure Data

Analysis Population Description

All patients treated population. Two menotrophin patients did not have pregnancy outcome data recorded in this timeframe but were later recorded as having live births so are included here as "YES" for ongoing pregnancy.

Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description:	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
Overall Number of Participants Analyzed	37	39
Measure Type: Number; Unit of Measure: percentage of participants
	37.8	33.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menotrophin, Follitropin Alfa
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.045
	Confidence Interval	95%; -0.170 to 0.260
	Estimation Comments	A two-sided 95% continuity-corrected confidence interval for the difference in percentages, based on the normal approximation

3. Secondary Outcome

Title	Participants With Varying Numbers of Follicles That Were Greater Than or Equal to 17 Millimeters
Description	The criterion for ovulation induction was three follicles ≥ 17 mm diameter as shown by pelvic ultrasound examination. Patients were assessed by pelvic ultrasound on the morning (prior to menotrophin or follitropin alfa administration) of Day 7 and, if appropriate, every 2 days thereafter (Days 9/11/13) until the criterion was met.
Time Frame	Day 7 and, if appropriate, every 2 days thereafter (Days 9/11/13)

Outcome Measure Data

Analysis Population Description

All treated patients population

Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description:	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
Overall Number of Participants Analyzed	37	39
Measure Type: Number; Unit of Measure: participants
Did not meet criterion	10	3
3 follicles ≥ 17 mm in diameter	11	11
4 follicles ≥ 17 mm in diameter	7	10
5 follicles ≥ 17 mm in diameter	2	10
6 follicles ≥ 17 mm in diameter	4	1
7 follicles ≥ 17 mm in diameter	0	0
8 follicles ≥ 17 mm in diameter	1	3
9 follicles ≥ 17 mm in diameter	0	0
10 follicles ≥ 17 mm in diameter	1	0
11-14 follicles ≥ 17 mm in diameter	0	0
15 follicles ≥ 17 mm in diameter	0	1
16 follicles ≥ 17 mm in diameter	1	0

4. Secondary Outcome

Title	Participants With Varying Numbers of Oocytes Retrieved
Description	Number of participants with grouped by the number of oocytes retrieved. Oocytes were retrieved following ovulation induction by subcutaneous administration of human chorionic gonadotrophin (hCG) in the form of choriogonadotropin alfa at a dose of 250 micrograms once participants reached the criteria of at least three follicles with >= 17mm in diameter.
Time Frame	Approximately study day 15

Outcome Measure Data

Analysis Population Description

All treated patients population.

Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description:	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
Overall Number of Participants Analyzed	23	29
Measure Type: Number; Unit of Measure: participants
0 oocytes retrieved	1	0
1 oocyte retrieved	1	1
2 oocytes retrieved	3	1
3 oocytes retrieved	3	1
4 oocytes retrieved	2	2
5 oocytes retrieved	2	5
6 oocytes retrieved	4	4
7 oocytes retrieved	2	2
8 oocytes retrieved	2	4
9 oocytes retrieved	2	2
10 oocytes retrieved	1	3
11 oocytes retrieved	0	0
12 oocytes retrieved	0	4
13 oocytes retrieved	0	1
14 oocytes retrieved	1	0
15 oocytes retrieved	0	3
16 oocytes retrieved	1	2
17-18 oocytes retrieved	0	0
19 oocytes retrieved	1	2
20 oocytes retrieved	0	0
21 oocytes retrieved	1	0
22 oocytes retrieved	0	0
23 oocytes retrieved	0	1

5. Secondary Outcome

Title	Participants With Varying Numbers of Pronuclear Stage Oocytes
Description	Number of participants with various groupings of pronuclear oocytes retrieved 16-20 hours after insemination.
Time Frame	Approximately study day 15

Outcome Measure Data

Analysis Population Description

All patients treated population

Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description:	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
Overall Number of Participants Analyzed	25	35
Measure Type: Number; Unit of Measure: participants
1 pronuclear stage oocyte	1	0
2 pronuclear stage oocytes	8	6
3 pronuclear stage oocytes	1	3
4 pronuclear stage oocytes	2	7
5 pronuclear stage oocytes	4	7
6 pronuclear stage oocytes	1	0
7 pronuclear stage oocytes	2	2
8 pronuclear stage oocytes	2	2
9 pronuclear stage oocytes	1	1
10 pronuclear stage oocytes	1	1
11 pronuclear stage oocytes	2	0
12 pronuclear stage oocytes	0	4
13 pronuclear stage oocytes	0	1
14-16 pronuclear stage oocytes	0	0
17 pronuclear stage oocytes	0	1

6. Secondary Outcome

Title	Participants With Varying Numbers of Embryos Transferred
Description	Number of participants with various categories of numbers of embryos transferred.
Time Frame	Approximately study day 17

Outcome Measure Data

Analysis Population Description

All patients treated population

Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description:	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
Overall Number of Participants Analyzed	24	33
Measure Type: Number; Unit of Measure: participants
0 embryos transferred	0	1
1 embryo transferred	3	1
2 embryos transferred	21	28
3 embryos transferred	0	3

7. Secondary Outcome

Title	Participants With Varying Numbers of Embryos Frozen
Description	Number of participants with different categories of number of embryos frozen.
Time Frame	Approximately study day 17

Outcome Measure Data

Analysis Population Description

All patients treated population

Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description:	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
Overall Number of Participants Analyzed	24	33
Measure Type: Number; Unit of Measure: participants
0 embryos frozen	16	22
1 embryo frozen	1	0
2 embryos frozen	2	1
3 embryos frozen	1	4
4 embryos frozen	4	2
5 embryos frozen	0	2
6-8 embryos frozen	0	0
9 embryos frozen	0	1
10 embryos frozen	0	1

8. Secondary Outcome

Title	Mean Number of Days Stimulated With Gonadotrophins
Description	Number of days stimulated with study drug until participant met the criteria for ovulation induction. Ovulation induction criteria is three follicles greater than or equal to 17 mm diameter as shown by pelvic ultrasound examination.
Time Frame	study days 1 - 13

Outcome Measure Data

Analysis Population Description

All patients treated population

Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description:	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
Overall Number of Participants Analyzed	37	39
Mean (Standard Deviation); Unit of Measure: days
	9.2 (1.71)	8.9 (1.07)

9. Secondary Outcome

Title	Pregnancy Outcomes
Description	Long term follow-up to determine the outcome of the pregnancy.
Time Frame	Approximately 10 months

Outcome Measure Data

Analysis Population Description

All patients treated population

Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description:	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
Overall Number of Participants Analyzed	17	17
Measure Type: Number; Unit of Measure: participants
Miscarriage	4	4
Pre-term: 1 live birth	1	1
Pre-term: 2 live births	2	3
Pre-term stillbirth	0	1
Full term: 1 live birth	7	6
Full term: 2 live births	3	2

10. Secondary Outcome

Title	Mean Endometrial Thickness
Description	Measurement performed on day of human chorionic gonadotrophin (hCG) administration/ovulation induction.
Time Frame	Day 7 or 9 or 11 or 13

Outcome Measure Data

Analysis Population Description

All patients treated population

Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description:	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
Overall Number of Participants Analyzed	27	38
Mean (Standard Deviation); Unit of Measure: millimeters
	11.7 (2.73)	11.0 (2.31)

11. Secondary Outcome

Title	Mean Estradiol Level
Description	Measurement on day of human chorionic gonadotrophin (hCG) administration / ovulation induction.
Time Frame	Day 7 or 9 or 11 or 13

Outcome Measure Data

Analysis Population Description

All patient treated population

Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description:	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
Overall Number of Participants Analyzed	27	38
Mean (Standard Deviation); Unit of Measure: picomoles / liter
	6706.6 (4109.26)	6268.3 (4132.11)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	The 'all patients treated' population is the same as the safety population in this study.
Arm/Group Title	Menotrophin	Follitropin Alfa
Arm/Group Description	Highly purified menotrophin sourced from human menopausal gonadotrophin (hMG)	A genetically engineered substitute for follicle stimulating hormone (recombinant FSH (rFSH)).
All-Cause Mortality
	Menotrophin	Follitropin Alfa
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Menotrophin	Follitropin Alfa
	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/37 (10.81%)	9/39 (23.08%)
Gastrointestinal disorders
Abdominal Pain † 1	0/37 (0.00%)	2/39 (5.13%)
Abdominal Pain Lower † 1	0/37 (0.00%)	1/39 (2.56%)
Constipation † 1	0/37 (0.00%)	1/39 (2.56%)
Vomiting † 1	0/37 (0.00%)	1/39 (2.56%)
General disorders
Pyrexia † 1	0/37 (0.00%)	1/39 (2.56%)
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous † 1	1/37 (2.70%)	3/39 (7.69%)
Abortion Imminent † 1	1/37 (2.70%)	0/39 (0.00%)
Renal and urinary disorders
Dysuria † 1	0/37 (0.00%)	1/39 (2.56%)
Reproductive system and breast disorders
Ovarian Hyperstimulation Syndrome † 1	2/37 (5.41%)	3/39 (7.69%)
Uterine Haemorrhage † 1	0/37 (0.00%)	1/39 (2.56%)
Vaginal Haemorrhage † 1	0/37 (0.00%)	1/39 (2.56%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 7.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Menotrophin	Follitropin Alfa
	Affected / at Risk (%)	Affected / at Risk (%)
Total	18/37 (48.65%)	21/39 (53.85%)
Gastrointestinal disorders
Abdominal Distension † 1	1/37 (2.70%)	4/39 (10.26%)
Abdominal Pain † 1	0/37 (0.00%)	2/39 (5.13%)
Abdominal Pain Lower † 1	1/37 (2.70%)	2/39 (5.13%)
Constipation † 1	0/37 (0.00%)	2/39 (5.13%)
Nausea † 1	3/37 (8.11%)	0/39 (0.00%)
Vomiting † 1	1/37 (2.70%)	3/39 (7.69%)
General disorders
Injection Site Bruising † 1	3/37 (8.11%)	2/39 (5.13%)
Injection Site Erythema † 1	6/37 (16.22%)	4/39 (10.26%)
Injection Site Haemorrhage † 1	0/37 (0.00%)	3/39 (7.69%)
Injection Site Pruritus † 1	7/37 (18.92%)	2/39 (5.13%)
Injection Site Rash † 1	0/37 (0.00%)	2/39 (5.13%)
Injection Site Swelling † 1	4/37 (10.81%)	4/39 (10.26%)
Infections and infestations
Nasopharyngitis † 1	2/37 (5.41%)	0/39 (0.00%)
Nervous system disorders
Dizziness † 1	1/37 (2.70%)	2/39 (5.13%)
Headache † 1	1/37 (2.70%)	6/39 (15.38%)
Reproductive system and breast disorders
Breast Tenderness † 1	1/37 (2.70%)	3/39 (7.69%)
Ovarian Hyperstimulation Syndrome † 1	2/37 (5.41%)	4/39 (10.26%)
Vaginal Haemorrhage † 1	2/37 (5.41%)	0/39 (0.00%)
Skin and subcutaneous tissue disorders
Pruritus † 1	0/37 (0.00%)	2/39 (5.13%)
Skin Reaction † 1	2/37 (5.41%)	3/39 (7.69%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 7.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The only disclosure restiction 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.

Results Point of Contact

• Name/Title: Clinical Development Support
• Organization: Ferring Pharmaceuticals
• EMail: DK0-Disclosure@ferring.com

• Responsible Party: Clinical Development Support, Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00257556
• Other Study ID Numbers: FE999906 CS004 (PROSPECT); 2004-001307-35 ( Registry Identifier: EudraCT )
• First Submitted: November 22, 2005
• First Posted: November 23, 2005
• Results First Submitted: January 8, 2010
• Results First Posted: February 26, 2010
• Last Update Posted: February 26, 2010