The Efficacy and Safety of FE 200486 in Treatment of Patients Suffering From Prostate Cancer

• Sponsor: Ferring Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00819247
• Collaborator: (none)
• Enrollment: 129
• Locations: 16
• Arms: 3
• Duration (Months): 17
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this trial was to select a dose of degarelix (FE 200486). Three groups of patients were treated for six months on different doses. The patients had blood samples taken and measured for Testosterone in order to determine the most efficient dose to provide fast and sustained castration. The patients came to the clinic for 16 visits and dependent on the blood sample results they were invited to return for additional blood samples on a two weekly basis.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Degarelix	Phase 2

Detailed Description

Degarelix was not FDA regulated at the time of the trial. After completion of the trial degarelix has been approved by the FDA and is thus an FDA regulated intervention.

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Six Month, Multi-centre, Open-labelled, 1:1:1 Randomised, Parallel Group Study Investigating the Efficacy and Safety of Three Dose Regimens of FE 200486 in Prostate Cancer Patients
• Study Start Date: Mar 1, 2001
• Actual Primary Completion Date: May 1, 2002
• Actual Study Completion Date: Aug 1, 2002

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Degarelix 80/80 + 40 Loading doses of Degarelix 80 mg (20 mg/mL) on Days 0 and 3. Maintenance doses of 40 mg (20 mg/mL) given on days 28, 56, 84, 112 and 140.	Drug: Degarelix; Given as a subcutaneous injection.; Other Names: FE 200486
Experimental: Degarelix 40/40 + 40 Loading doses of Degarelix 40 mg (20 mg/mL) on Days 0 and 3. Maintenance doses of 40 mg (20 mg/mL) given on days 28, 56, 84, 112 and 140.	Drug: Degarelix; Given as a subcutaneous injection.; Other Names: FE 200486
Experimental: Degarelix 80 + 20 Loading dose of Degarelix 80 mg (20 mg/mL) on Day 0. Maintenance doses of 20 mg (10 mg/mL) given on days 28, 56, 84, 112 and 140.	Drug: Degarelix; Given as a subcutaneous injection.; Other Names: FE 200486

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Testosterone <0.5 Nanogram/Milliliter [Weeks 1,2,4,8,12,16,20,24]

Secondary Outcome Measures

1. Number of Participants With Testosterone < 0.5 Nanogram/Milliliter at All Visits Between Weeks 4-24 [Weeks 4-24]

2. Number of Participants Not Meeting a Testosterone Withdrawal Criterion Between Weeks 4-24 [Weeks 4-24]

   Participants with one testoterone value > 1.0 nanogram/millliliter or two consecutive values between 0.5-1.0 nanogram/milliliter were withdrawn from the study due to insufficient response.

3. Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen [Six months]

   Participants who met at least one of the three criteria for inadequate response on prostate-specific antigen levels (PA). (1) >=25 percent and/or 50 nanogram/milliliter compared to baseline (2) reduction of <=50% compared to baseline at week 12 (3) increase of >=10 nanogram/milliliter compared to nadir from week 4.

4. Number of Participants With Normal Prostate-specific Antigen Levels During the Study [Weeks 12, 24]

   The number of participants whose prostate-specific antigen levels at weeks 12 and 24 were <= 4 nanogram/millliliter (normal level).

5. The Number of Participants With Abnormal Liver Function Tests [Six months]

   The number of participants who had abnormal [defined as above upper limit of normal range (ULN)] alanine aminotransferase (ALT), participants with ALT increases > 3x ULN, and participants with ALT increases > 3x ULN with concurrent increases in bilirubin > 1.5 ULN.

6. Percentage Change in Vital Signs and Body Weight [Baseline and Six months]

   Percentage changes in vital signs (systolic and diastolic blood pressure and pulse) and body weight at the end of trial as compared to baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent before any trial related activity

• Proven prostate cancer with a need for endocrine treatment

• Testosterone level within the normal range for the age

Exclusion Criteria:

• Previous or current hormonal treatment of prostate cancer

• Candidate for prostatectomy or radiotherapy

• History of severe asthma, anaphylactic reactions or Quincke's Oedema

• Hypersensitivity towards any component of FE200486

• Cancer disease within the last ten years except for prostate cancer and some skin cancers

• Presenting with significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, haematological, dermatological or infectious disorder. In addition any other condition such as excessive alcohol or drug abuse that may interfere with trial participation or influence the conclusion of the trial as judged by the investigator

• Mental incapacity or language barrier

• Having received an investigational product within the last 12 weeks preceding the trial

• Previous participation in this trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ayr Hospital	Ayr		United Kingdom
2	Bristol Royal Infirmary	Bristol		United Kingdom
3	Southmead Hospital	Bristol		United Kingdom
4	St. Richards Hospital	Chichester		United Kingdom
5	Glan Clwyd Hospital	Denbighshire		United Kingdom
6	Ninewells Hospital	Dundee		United Kingdom
7	Southern General Hospital	Glasgow		United Kingdom
8	Leicester General Hospital	Leicester		United Kingdom
9	Chelsea and Westminster Hospital	London		United Kingdom
10	Kings College Hospital	London		United Kingdom
11	St. Bartholemews Hospital	London		United Kingdom
12	Derriford Hospital	Plymouth		United Kingdom
13	Lister Hospital	Stevenage		United Kingdom
14	Stirling Royal Infirmary	Stirling		United Kingdom
15	Morriston Hospital	Swansea		United Kingdom
16	Pindersfields General Hospital	Wakefield		United Kingdom

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: NCT00819247
• Other Study ID Numbers: FE200486 CS02
• First Posted: Jan 8, 2009
• Last Update Posted: May 20, 2011
• Last Verified: May 1, 2011

• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	One hundred and fifty-nine participants were screened. One hundred and twenty-nine participants were randomised, two of these participants withdrew before receiving any treatment.

Arm/Group Title	Degarelix 80/80 + 40	Degarelix 40/40 + 40	Degarelix 80 + 20
Arm/Group Description	Loading doses of Degarelix 80 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading doses of Degarelix 40 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading dose of Degarelix 80 mg on Day 0. Maintenance doses of 20 mg given on days 28, 56, 84, 112 and 140.
Period Title: Overall Study
STARTED	43	46	40
Randomized	43	46	40
Intent-to-treat Population	42	46	39
Per Protocol Population	38	44	38
COMPLETED	32	30	26
NOT COMPLETED	11	16	14

Baseline Characteristics

Arm/Group Title	Degarelix 80/80 + 40	Degarelix 40/40 + 40	Degarelix 80 + 20	Total
Arm/Group Description	Loading doses of Degarelix 80 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading doses of Degarelix 40 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading dose of Degarelix 80 mg on Day 0. Maintenance doses of 20 mg given on days 28, 56, 84, 112 and 140.	Total of all reporting groups
Overall Participants	43	46	40	129
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	6 14%	5 10.9%	7 17.5%	18 14%
>=65 years	37 86%	41 89.1%	33 82.5%	111 86%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.4 (6.6)	73.7 (7.2)	71.8 (7.1)	72.7 (7.0)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	43 100%	46 100%	40 100%	129 100%
Race/Ethnicity, Customized (participants) [Number]
White	42 97.7%	43 93.5%	37 92.5%	122 94.6%
Black	1 2.3%	3 6.5%	1 2.5%	5 3.9%
Oriental / Asian	0 0%	0 0%	0 0%	0 0%
Afro-carribean	0 0%	0 0%	1 2.5%	1 0.8%
Indian	0 0%	0 0%	1 2.5%	1 0.8%
Region of Enrollment (participants) [Number]
United Kingdom	43 100%	46 100%	40 100%	129 100%
Participant Counts by Gleason Score (participants) [Number]
unknown	1 2.3%	1 2.2%	1 2.5%	3 2.3%
2-4	3 7%	4 8.7%	2 5%	9 7%
5-6	11 25.6%	7 15.2%	11 27.5%	29 22.5%
7-10	28 65.1%	34 73.9%	26 65%	88 68.2%
Stage of Prostate Cancer (participants) [Number]
Localized	8 18.6%	9 19.6%	5 12.5%	22 17.1%
Locally advanced	21 48.8%	21 45.7%	18 45%	60 46.5%
Metastatic	11 25.6%	14 30.4%	17 42.5%	42 32.6%
Not classifiable	3 7%	2 4.3%	0 0%	5 3.9%
Body Mass Index (kilogram per square meter) [Median (Full Range) ]
Median (Full Range) [kilogram per square meter]	26.2	26.6	25.2	26.1
Days Since Diagnosis of Prostate Cancer (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	52.7 (116.0)	153.8 (518.1)	88.8 (370.0)	99.9 (377.2)
Serum Prostate-Specific Antigen level (nanogram/milliliter) [Median (Full Range) ]
Median (Full Range) [nanogram/milliliter]	50.3	64.6	82.9	61.1
Serum Testosterone level (nanogram/milliliter) [Median (Full Range) ]
Median (Full Range) [nanogram/milliliter]	3.7	4.1	4.8	4.0

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Testosterone <0.5 Nanogram/Milliliter
Time Frame	Weeks 1,2,4,8,12,16,20,24

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	Degarelix 80/80 + 40	Degarelix 40/40 + 40	Degarelix 80 + 20
Arm/Group Description	Loading doses of Degarelix 80 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading doses of Degarelix 40 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading dose of Degarelix 80 mg on Day 0. Maintenance doses of 20 mg given on days 28, 56, 84, 112 and 140.
Measure Participants	38	44	38
Week 1 (n=38, 44, 38)	38 88.4%	32 69.6%	27 67.5%
Week 2 (n=38, 44, 38)	38 88.4%	36 78.3%	33 82.5%
Week 4 (n=38, 36, 33)	38 88.4%	35 76.1%	31 77.5%
Week 8 (n=36, 36, 31)	36 83.7%	36 78.3%	31 77.5%
Week 12 (n=34, 34, 31)	34 79.1%	34 73.9%	30 75%
Week 16 (n=34, 32, 30)	33 76.7%	31 67.4%	27 67.5%
Week 20 (n=33, 31, 28)	31 72.1%	30 65.2%	25 62.5%
Week 24 (n=31, 29, 25)	28 65.1%	27 58.7%	22 55%

2. Secondary Outcome

Title	Number of Participants With Testosterone < 0.5 Nanogram/Milliliter at All Visits Between Weeks 4-24
Time Frame	Weeks 4-24

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	Degarelix 80/80 + 40	Degarelix 40/40 + 40	Degarelix 80 + 20
Arm/Group Description	Loading doses of Degarelix 80 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading doses of Degarelix 40 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading dose of Degarelix 80 mg on Day 0. Maintenance doses of 20 mg given on days 28, 56, 84, 112 and 140.
Measure Participants	32	29	27
Number [participants]	28 65.1%	27 58.7%	20 50%

3. Secondary Outcome

Title	Number of Participants Not Meeting a Testosterone Withdrawal Criterion Between Weeks 4-24
Description	Participants with one testoterone value > 1.0 nanogram/millliliter or two consecutive values between 0.5-1.0 nanogram/milliliter were withdrawn from the study due to insufficient response.
Time Frame	Weeks 4-24

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	Degarelix 80/80 + 40	Degarelix 40/40 + 40	Degarelix 80 + 20
Arm/Group Description	Loading doses of Degarelix 80 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading doses of Degarelix 40 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading dose of Degarelix 80 mg on Day 0. Maintenance doses of 20 mg given on days 28, 56, 84, 112 and 140.
Measure Participants	32	29	27
Number [participants]	29 67.4%	29 63%	25 62.5%

4. Secondary Outcome

Title	Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen
Description	Participants who met at least one of the three criteria for inadequate response on prostate-specific antigen levels (PA). (1) >=25 percent and/or 50 nanogram/milliliter compared to baseline (2) reduction of <=50% compared to baseline at week 12 (3) increase of >=10 nanogram/milliliter compared to nadir from week 4.
Time Frame	Six months

Outcome Measure Data

Analysis Population Description

per protocol population

Arm/Group Title	Degarelix 80/80 + 40	Degarelix 40/40 + 40	Degarelix 80 + 20
Arm/Group Description	Loading doses of Degarelix 80 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading doses of Degarelix 40 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading dose of Degarelix 80 mg on Day 0. Maintenance doses of 20 mg given on days 28, 56, 84, 112 and 140.
Measure Participants	38	44	38
>=25% and/or 50 ng/mL compared to baseline	0 0%	0 0%	0 0%
<=50% compared to baseline	0 0%	0 0%	0 0%
>=10 ng/mL compared to nadir	1 2.3%	6 13%	1 2.5%

5. Secondary Outcome

Title	Number of Participants With Normal Prostate-specific Antigen Levels During the Study
Description	The number of participants whose prostate-specific antigen levels at weeks 12 and 24 were <= 4 nanogram/millliliter (normal level).
Time Frame	Weeks 12, 24

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Degarelix 80/80 + 40	Degarelix 40/40 + 40	Degarelix 80 + 20
Arm/Group Description	Loading doses of Degarelix 80 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading doses of Degarelix 40 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading dose of Degarelix 80 mg on Day 0. Maintenance doses of 20 mg given on days 28, 56, 84, 112 and 140.
Measure Participants	38	44	38
Week 12 (n=34, 34, 31)	18 41.9%	18 39.1%	16 40%
Week 24 (n=31, 29, 25)	18 41.9%	18 39.1%	17 42.5%

6. Secondary Outcome

Title	The Number of Participants With Abnormal Liver Function Tests
Description	The number of participants who had abnormal [defined as above upper limit of normal range (ULN)] alanine aminotransferase (ALT), participants with ALT increases > 3x ULN, and participants with ALT increases > 3x ULN with concurrent increases in bilirubin > 1.5 ULN.
Time Frame	Six months

Outcome Measure Data

Analysis Population Description

Randomized (Safety) population

Arm/Group Title	Degarelix 80/80 + 40	Degarelix 40/40 + 40	Degarelix 80 + 20
Arm/Group Description	Loading doses of Degarelix 80 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading doses of Degarelix 40 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading dose of Degarelix 80 mg on Day 0. Maintenance doses of 20 mg given on days 28, 56, 84, 112 and 140.
Measure Participants	43	46	40
Alanine aminotransferase (ALT) above upper limit	13 30.2%	14 30.4%	12 30%
ALT levels >3x upper limit	0 0%	1 2.2%	1 2.5%
ALT levels >3x and bilirubin >1.5x upper limit	0 0%	0 0%	1 2.5%

7. Secondary Outcome

Title	Percentage Change in Vital Signs and Body Weight
Description	Percentage changes in vital signs (systolic and diastolic blood pressure and pulse) and body weight at the end of trial as compared to baseline.
Time Frame	Baseline and Six months

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	Degarelix 80/80 + 40	Degarelix 40/40 + 40	Degarelix 80 + 20
Arm/Group Description	Loading doses of Degarelix 80 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading doses of Degarelix 40 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.	Loading dose of Degarelix 80 mg on Day 0. Maintenance doses of 20 mg given on days 28, 56, 84, 112 and 140.
Measure Participants	43	46	40
Diastolic blood pressure	0.0	-0.6	0.0
Systolic blood pressure	-3.7	-2.4	0.0
Pulse	-3.1	0.0	-1.5
Weight	2.8	2.6	3.5

Adverse Events

Arm/Group Title	Degarelix 80/80 + 40		Degarelix 40/40 + 40		Degarelix 80 + 20
Arm/Group Description	Loading doses of Degarelix 80 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.		Loading doses of Degarelix 40 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140.		Loading dose of Degarelix 80 mg on Day 0. Maintenance doses of 20 mg given on days 28, 56, 84, 112 and 140.
All Cause Mortality
	Degarelix 80/80 + 40		Degarelix 40/40 + 40		Degarelix 80 + 20
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Degarelix 80/80 + 40		Degarelix 40/40 + 40		Degarelix 80 + 20
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/ (NaN)		8/ (NaN)		6/ (NaN)
Blood and lymphatic system disorders
Anaemia	1/43 (2.3%)	1	1/46 (2.2%)	1	0/40 (0%)	0
Cardiac disorders
Angina pectoris	1/43 (2.3%)	1	0/46 (0%)	0	1/40 (2.5%)	1
Myocardial infarction	1/43 (2.3%)	1	1/46 (2.2%)	1	0/40 (0%)	0
Cardiac failure congestive	1/43 (2.3%)	1	0/46 (0%)	0	0/40 (0%)	0
Gastrointestinal disorders
Nausea	0/43 (0%)	0	1/46 (2.2%)	2	0/40 (0%)	0
Rectal haemorrhage	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
Vomiting	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
General disorders
Asthenia	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
Catheter related complication	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
Condition aggravated	0/43 (0%)	0	0/46 (0%)	0	1/40 (2.5%)	1
Hepatobiliary disorders
Hepatic function abnormal	0/43 (0%)	0	0/46 (0%)	0	1/40 (2.5%)	1
Immune system disorders
Hypersensitivity	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
Infections and infestations
Lobar pneumonia	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
Sepsis	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
Injury, poisoning and procedural complications
Post procedural haemorrhage	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/43 (0%)	0	0/46 (0%)	0	1/40 (2.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
Nervous system disorders
Cerebral haemorrhage	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
Cerebrovascular accident	0/43 (0%)	0	0/46 (0%)	0	1/40 (2.5%)	1
Syncope	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
Psychiatric disorders
Depression	1/43 (2.3%)	1	0/46 (0%)	0	1/40 (2.5%)	1
Alcoholism	1/43 (2.3%)	1	0/46 (0%)	0	0/40 (0%)	0
Renal and urinary disorders
Bladder obstruction	0/43 (0%)	0	0/46 (0%)	0	1/40 (2.5%)	1
Calculus bladder	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
Dysuria	0/43 (0%)	0	0/46 (0%)	0	1/40 (2.5%)	1
Urine flow decreased	0/43 (0%)	0	1/46 (2.2%)	1	0/40 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/43 (0%)	0	1/46 (2.2%)	2	0/40 (0%)	0
Other (Not Including Serious) Adverse Events
	Degarelix 80/80 + 40		Degarelix 40/40 + 40		Degarelix 80 + 20
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/ (NaN)		38/ (NaN)		32/ (NaN)
Gastrointestinal disorders
Diarrhoea	6/43 (14%)	9	2/46 (4.3%)	2	2/40 (5%)	4
Constipation	3/43 (7%)	3	1/46 (2.2%)	1	1/40 (2.5%)	1
Inguinal hernia	1/43 (2.3%)	1	1/46 (2.2%)	1	2/40 (5%)	2
Dyspepsia	0/43 (0%)	0	1/46 (2.2%)	1	2/40 (5%)	2
Abdominal pain	0/43 (0%)	0	0/46 (0%)	0	2/40 (5%)	2
General disorders
Fatigue	2/43 (4.7%)	2	4/46 (8.7%)	5	0/40 (0%)	0
Suprapubic pain	0/43 (0%)	0	0/46 (0%)	0	2/40 (5%)	2
Infections and infestations
Nasopharyngitis	5/43 (11.6%)	6	7/46 (15.2%)	7	5/40 (12.5%)	5
Urinary tract infection	3/43 (7%)	5	1/46 (2.2%)	1	2/40 (5%)	2
Investigations
Weight increased	0/43 (0%)	0	0/46 (0%)	0	2/40 (5%)	2
Musculoskeletal and connective tissue disorders
Back pain	3/43 (7%)	3	3/46 (6.5%)	3	2/40 (5%)	2
Arthralgia	0/43 (0%)	0	3/46 (6.5%)	3	0/40 (0%)	0
Nervous system disorders
Headache	4/43 (9.3%)	5	2/46 (4.3%)	2	3/40 (7.5%)	4
Lethargy	2/43 (4.7%)	2	3/46 (6.5%)	4	1/40 (2.5%)	1
Renal and urinary disorders
Dysuria	3/43 (7%)	4	0/46 (0%)	0	2/40 (5%)	4
Pollakiuria	0/43 (0%)	0	1/46 (2.2%)	1	2/40 (5%)	2
Reproductive system and breast disorders
Testicular atrophy	3/43 (7%)	3	2/46 (4.3%)	2	4/40 (10%)	4
Respiratory, thoracic and mediastinal disorders
Cough	2/43 (4.7%)	2	2/46 (4.3%)	2	2/40 (5%)	2
Skin and subcutaneous tissue disorders
Hyperhidrosis	3/43 (7%)	3	3/46 (6.5%)	3	1/40 (2.5%)	1
Skin reaction	3/43 (7%)	3	0/46 (0%)	0	0/40 (0%)	0
Vascular disorders
Hot flush	21/43 (48.8%)	22	21/46 (45.7%)	21	22/40 (55%)	25
Flushing	4/43 (9.3%)	4	6/46 (13%)	6	2/40 (5%)	2
Hypertension	3/43 (7%)	3	2/46 (4.3%)	2	1/40 (2.5%)	1

Limitations/Caveats

[Not Specified]

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.