Exploratory Study Assessing Synchronisation of Egg Sacs With Degarelix

• Sponsor: Ferring Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00434122
• Collaborator: (none)
• Enrollment: 85
• Locations: 4
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 21.3
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

The main purpose of this clinical research study is to investigate if degarelix can synchronise the growth of the egg sacs in the ovaries and if degarelix has any effect on the lining of the womb.

Condition or Disease	Intervention/Treatment	Phase
Infertility, Female	Drug: Degarelix mid-luteal, 2.5 mg; Drug: Placebo	Phase 2

Detailed Description

For the primary end-point (data collected on Stimulation Day 1), the study will compare degarelix 2.5 mg administered in the mid-luteal phase to placebo administered in the mid-luteal phase.

After Stimulation Day 1 the placebo group will be split into two groups: a degarelix 2.5 mg follicular group and a ganirelix 0.25 mg group.

Study Design

• Study Type: Interventional
• Actual Enrollment: 85 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Prevention
• Official Title: A Randomised, Assessor-blind, Parallel Groups, Multi-centre, Exploratory Study Assessing the Impact of Subcutaneous Administration of Degarelix 2.5 mg on Synchronisation of Follicle Cohort Compared to Placebo and Evaluating the Effects of Degarelix 2.5 mg Started in the Mid-luteal or Early Follicular Phase on Endometrial Receptivity Compared to a Fixed Gonadotrophin Releasing Hormone Antagonist Protocol in Oocyte Donors Undergoing Controlled Ovarian Hyperstimulation for Assisted Reproductive Technologies
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Degarelix mid-luteal, 2.5 mg Degarelix 2.5 mg will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak and on Stimulation Day 6. Placebo will be injected SC on Stimulation Day 1.	Drug: Degarelix mid-luteal, 2.5 mg; Degarelix 2.5 mg will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak and on Stimulation Day 6. Placebo will be injected SC on Stimulation Day 1.
Placebo Comparator: Placebo Placebo will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak. Degarelix 2.5 mg will be injected SC on Stimulation Day 1 and Stimulation Day 6. or Placebo will be injected SC 7 days after LH peak and on Stimulation Day 1. Ganirelix 0.25 mg will be injected SC daily from Stimulation Day 6 until the last stimulation day.	Drug: Placebo; Placebo will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak. Degarelix 2.5 mg will be injected SC on Stimulation Day 1 and Stimulation Day 6. or Placebo will be injected SC 7 days after LH peak and on Stimulation Day 1. Ganirelix 0.25 mg will be injected SC daily from Stimulation Day 6 until the last stimulation day.

Outcome Measures

Primary Outcome Measures

1. Coefficient of Variation of Follicular Sizes on Stimulation Day 1 (Follicles ≥ 2 mm) [Stimulation Day 1]

   Explanation of the term "coefficient of variation": The coefficient of variation is a normalized measure of dispersion of a probability distribution.

Secondary Outcome Measures

1. Frequency of Oocyte Donors With Adequate Secretory Transformation at the Endometrial Histology Evaluation 7 Days After Injection With Human Chorionic Gonadotrophin (hCG) [7 days after hCG injection]

   An adequate secretory endometrium 7 days after hCG injection was defined as secretory in the histological classification and with endometrial dating corresponding to the expected cycle day ±1 day.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria

• Signed Informed Consent Form, prior to screening evaluations

• In good physical and mental health

• Pre-menopausal females between the ages of 18-35 years (both inclusive) at the time of randomisation

• Regular menstrual cycles of 26-35 days duration (both inclusive), presumed to be ovulatory

• Body mass index (BMI) between 18 and 29 kg/m2 (both inclusive)

• Willing to donate the retrieved oocytes

• Willing to use an adequate barrier method of contraception from informed consent to Day hCG injection +7 and to use an adequate barrier or hormonal method of contraception from Day hCG injection +7 to the end-of-study visit

Exclusion Criteria

• Abnormal karyotype

• Any known clinically significant systemic disease (e.g., insulin dependent diabetes)

• Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) which can compromise participation in the study

• Diagnosed with polycystic ovarian syndrome or endometriosis stage III/IV

• Diagnosed as "poor responder"

• History of recurrent miscarriage (defined as three consecutive spontaneous losses before weeks 24 of pregnancy)

• Pregnancy or lactation

• Use of any investigational drug during 3 months prior to start of the current COH cycle

• Previous participation in the study

• Hypersensitivity to any trial product

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UZ Brussel	Brussels		Belgium
2	ISCARE IVF a.s.	Prague		Czech Republic
3	IVI-Madrid	Madrid		Spain
4	IVI-Valencia	Valencia		Spain

Sponsors and Collaborators

• Ferring Pharmaceuticals

Investigators

• Study Director: Clinical Development Support, Ferring Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00434122
• Other Study ID Numbers: FE200486 CS24
• First Posted: Feb 12, 2007
• Last Update Posted: Jun 2, 2011
• Last Verified: May 1, 2011

• Keywords provided by , ,: Assisted Reproductive Technology (ART); oocyte donors undergoing controlled ovarian hyperstimulation for assisted reproductive technologies
• Additional relevant MeSH terms: Infertility; Infertility, Female

Study Results

Participant Flow

Arm/Group Title	Degarelix Mid-luteal, 2.5 mg	Placebo
Arm/Group Description	Degarelix 2.5 mg will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak and on Stimulation Day 6. Placebo will be injected SC on Stimulation Day 1.	Placebo will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak. Degarelix 2.5 mg will be injected SC on Stimulation Day 1 and Stimulation Day 6. or Placebo will be injected SC 7 days after LH peak and on Stimulation Day 1. Ganirelix 0.25 mg will be injected SC daily from Stimulation Day 6 until the last stimulation day.
Period Title: Overall Study
STARTED	42	43
Intention-to-treat (ITT) Population	39	39
COMPLETED	36	36
NOT COMPLETED	6	7

Baseline Characteristics

Arm/Group Title	Degarelix Mid-luteal, 2.5 mg	Placebo	Total
Arm/Group Description	Degarelix 2.5 mg will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak and on Stimulation Day 6. Placebo will be injected SC on Stimulation Day 1.	Placebo will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak. Degarelix 2.5 mg will be injected SC on Stimulation Day 1 and Stimulation Day 6. or Placebo will be injected SC 7 days after LH peak and on Stimulation Day 1. Ganirelix 0.25 mg will be injected SC daily from Stimulation Day 6 until the last stimulation day.	Total of all reporting groups
Overall Participants	39	39	78
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	39 100%	39 100%	78 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.9 (4.1)	28.0 (3.9)	28.4 (4.0)
Sex: Female, Male (Count of Participants)
Female	39 100%	39 100%	78 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Czech Republic	7 17.9%	7 17.9%	14 17.9%
Spain	27 69.2%	26 66.7%	53 67.9%
Belgium	5 12.8%	6 15.4%	11 14.1%

Outcome Measures

1. Primary Outcome

Title	Coefficient of Variation of Follicular Sizes on Stimulation Day 1 (Follicles ≥ 2 mm)
Description	Explanation of the term "coefficient of variation": The coefficient of variation is a normalized measure of dispersion of a probability distribution.
Time Frame	Stimulation Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Degarelix Mid-luteal, 2.5 mg	Placebo
Arm/Group Description	Degarelix 2.5 mg will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak and on Stimulation Day 6. Placebo will be injected SC on Stimulation Day 1.	Placebo will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak. Degarelix 2.5 mg will be injected SC on Stimulation Day 1 and Stimulation Day 6. or Placebo will be injected SC 7 days after LH peak and on Stimulation Day 1. Ganirelix 0.25 mg will be injected SC daily from Stimulation Day 6 until the last stimulation day.
Measure Participants	39	39
Mean (Standard Deviation) [Percentage]	36.7 (5.6)	39.2 (9.5)

2. Secondary Outcome

Title	Frequency of Oocyte Donors With Adequate Secretory Transformation at the Endometrial Histology Evaluation 7 Days After Injection With Human Chorionic Gonadotrophin (hCG)
Description	An adequate secretory endometrium 7 days after hCG injection was defined as secretory in the histological classification and with endometrial dating corresponding to the expected cycle day ±1 day.
Time Frame	7 days after hCG injection

Outcome Measure Data

Analysis Population Description

Subjects with evaluable endometrial biopsies 7 days after injection with hCG.

Arm/Group Title	Degarelix Mid-luteal, 2.5 mg	Degarelix Follicular, 2.5 mg	Ganirelix, 0.25 mg
Arm/Group Description	Degarelix 2.5 mg will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak and on Stimulation Day 6. Placebo will be injected SC on Stimulation Day 1.	Placebo will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak. Degarelix 2.5 mg will be injected SC on Stimulation Day 1 and Stimulation Day 6	Placebo will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak and on Stimulation Day 1. Ganirelix 0.25 mg will be injected SC daily from Stimulation Day 6 until the last stimulation day.
Measure Participants	32	14	16
Number [Participants]	31 79.5%	11 28.2%	14 17.9%

Adverse Events

Time Frame	From signed informed consent till end-of-trial visit (approximately 12 +/- 2 weeks after oocyte retrieval)
Adverse Event Reporting Description	Evaluated at each trial visit
Arm/Group Title	Degarelix, 2.5 mg		Ganirelix, 0.25 mg
Arm/Group Description	Combination of these two groups: Degarelix Mid-luteal 2.5 mg and Degarelix Follicular 2.5 mg. Degarelix Mid-luteal, 2.5 mg: Degarelix 2.5 mg will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak and on Stimulation Day 6. Placebo will be injected SC on Stimulation Day 1. Degarelix Follicular, 2.5 mg: Placebo will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak. Degarelix 2.5 mg will be injected SC on Stimulation Day 1 and Stimulation Day 6.		Placebo will be injected SC 7 days after LH peak and on Stimulation Day 1. Ganirelix 0.25 mg will be injected SC daily from Stimulation Day 6 until the last stimulation day.
All Cause Mortality
	Degarelix, 2.5 mg		Ganirelix, 0.25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Degarelix, 2.5 mg		Ganirelix, 0.25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/63 (1.6%)		0/22 (0%)
Infections and infestations
Cellulitis	1/63 (1.6%)	1	0/22 (0%)	0
Other (Not Including Serious) Adverse Events
	Degarelix, 2.5 mg		Ganirelix, 0.25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/63 (11.1%)		4/22 (18.2%)
General disorders
Injection site erythema	3/63 (4.8%)	3	0/22 (0%)	0
Immune system disorders
Allergy to arthropod bite	0/63 (0%)	0	1/22 (4.5%)	1
Psychiatric disorders
Mood swings	3/63 (4.8%)	3	0/22 (0%)	0
Reproductive system and breast disorders
Menstruation delayed	1/63 (1.6%)	1	2/22 (9.1%)	2
Uterine polyp	0/63 (0%)	0	1/22 (4.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.