Study Investigating the Pharmacokinetics, Pharmacodynamics and Safety of FE200486

• Sponsor: Ferring Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00117949
• Collaborator: (none)
• Enrollment: 82
• Locations: 12
• Arms: 4
• Duration (Months): 21
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Population pharmacokinetic and pharmacodynamic data from Study FE200486 CS06 and FE200486 CS02 provided further knowledge of the optimal dose regimens for FE200486 (degarelix). Both studies were to guide dose selection for phase III. In addition, safety and tolerance data were generated.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multi-Center, Ascending, Single Dose Study Investigating the Pharmacokinetics, Pharmacodynamics and Safety of FE200486
• Study Start Date: Apr 1, 2002
• Actual Primary Completion Date: Jan 1, 2004
• Actual Study Completion Date: Jan 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Degarelix 40 mg Degarelix 40 mg (10 mg/mL)	Drug: Degarelix; One dose (2 x 2 mL) of degarelix 40 mg (10 mg/mL), subcutaneous injection.; Other Names: FE200486
Experimental: Degarelix 80 mg Degarelix 80 mg (20 mg/mL)	Drug: Degarelix; One dose (2 x 2 mL) of degarelix 80 mg (20 mg/mL), subcutaneous injection.; Other Names: FE200486
Experimental: Degarelix 120 mg Degarelix 120 mg (30 mg/mL)	Drug: Degarelix; One dose (2 x 2 mL) of degarelix 120 mg (30 mg/mL), subcutaneous injection.; Other Names: FE200486
Experimental: Degarelix 160 mg Degarelix 160 mg (40 mg/mL)	Drug: Degarelix; One dose (2 x 2 mL) of degarelix 160 mg (40 mg/mL), subcutaneous injection.; Other Names: FE200486

Outcome Measures

Primary Outcome Measures

1. Time to Meet Insufficient Testosterone Response [3 months]

   Figures in the table are Kaplan-Meier estimates of the time to meeting insufficient testosterone response. Insufficient testosterone response was defined as testosterone >1.0 ng/mL at one visit or testosterone 0.5-1.0 at two consecutive visits.

2. Number of Participants With Testostestone Serum Levels Below 0.5 ng/mL for at Least 28 Days [28 days]

   The number of participants suppressed for at least 28 days was defined as the estimated "survival probability" at time=Day 28.

Secondary Outcome Measures

1. Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). [1, 3, 7, 14, 21, 28, 42 days]

   Time to testosterone castration was calculated as the number of days from dosing to the first scheduled visit when testosterone was less than 0.5 ng/mL. The figures in the table present the number of participants who were castrated after 1, 3, 7, 14, 21, 28, and 42 days.

2. Number of Participants With Sufficient Testosterone Suppression for at Least 84 Days [3 months]

   Sufficient testosterone suppression was defined as not meeting an insufficient testosterone response criterion. Insufficient testosterone response was defined as testosterone >1.0 ng/mL at one visit or testosterone 0.5-1.0 at two consecutive visits.

3. Time to 50% Reduction in Prostate-specific Antigen Levels [3 months]

   The time to 50% prostate-specific antigen (PSA) reduction from baseline was defined as the median number of days from dosing to the first visit where a 50% reduction in PSA level was reached.

4. Time to 90% Reduction in Prostate-specific Antigen Levels [3 months]

   The time to 90% prostate-specific antigen (PSA) reduction from baseline was defined as the median number of days from dosing to the first visit where a 90% reduction in PSA level was reached.

5. Liver Function Tests [3 months]

   The number of participants who had abnormal (defined as above upper limit of normal range (ULN)) alanine aminotransferase (ALT) levels, aspartate aminotransferas levels, and bilirubin levels plus the number of participants who had ALT increases >3x ULN and ALT increases >3x ULN with concurrently increased bilirubin >1.5 ULN.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Each patient must meet the following inclusion criteria before entry into the study:

• Has given written consent before any study related activity is performed (A study related activity is defined as any procedure that would not have been performed during the normal management of the patient.)

• Is a male patient with histologically proven adenocarcinoma of the prostate (all stages) in whom endocrine treatment is indicated, except for neoadjuvant hormonal therapy. For patients, prostate-specific antigen (PSA) increases on two consecutive determinations at least 2 weeks apart prior to Visit 1 must be documented.

• Is at least 18 years.

• Has an ECOG score of 2.

• Has a baseline testosterone level within the age specific normal range as measured by the central laboratory.

• Has a PSA value of 2 ng/mL as measured by the central laboratory.

• Has a life expectancy of at least 6 months.

Exclusion Criteria:

Any patient meeting one or more of the following exclusion criteria will not be entered into the study:

• Previous or present hormonal management of prostate cancer (surgical castration or other hormonal manipulation, e.g. GnRH agonists, GnRH antagonists, antiandrogens, estrogens, PC-Spec) except for neoadjuvant hormonal therapy of < 6 months duration and completed > 6 months prior to Visit 1.

• Requires hormonal therapy for neoadjuvant purposes.

• Is recently (within the last 12 weeks preceding Visit 1) or presently treated with any other drug modifying the testosterone level or function.

• Is considered to be a candidate for curative therapy, i.e., radical prostatectomy or radiotherapy within 6 months after Visit 1.

• Has a history of severe asthma requiring daily treatment with inhalation steroids, angioedema or anaphylactic reactions.

• Has hypersensitivity towards any component of the investigational product.

• Has had a cancer disease within the last 10 years except for prostate cancer, and surgically removed basocellular or squamous cell carcinoma of the skin.

• Has a clinically significant neurologic, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, dermatological or infectious disorder or any other condition, including excessive alcohol or drug abuse, which may interfere with trial participation, or which may affect the conclusion of the study, as judged by the investigator.

• Any clinically significant laboratory abnormalities which, in the judgment of the investigator, would interfere with the patient's participation in this study or evaluation of study results (liver transaminases must be within normal limits).

• Has a mental incapacity or language barrier precluding adequate understanding or co-operation.

• Has received an investigational drug within the last 12 weeks preceding Visit 1.

• Has previously participated in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Advanced Urology Medical Center	Anaheim	California	United States	92801
2	South Orange County Medical Research Center	Laguna Woods,	California	United States	92653
3	San Bernardino Urological Associates Medical Group	San Bernardino	California	United States	92404
4	Western Clinical Research	Torrance	California	United States	90505
5	Urology Associate PC'	Denver	Colorado	United States	80210
6	SW Florida Urological Associates	Fort Myers	Florida	United States	33907
7	Pinellas Urology, Inc.	St. Petersburg	Florida	United States	33710
8	Drs. Werner, Murdock & Francis, PA	Greenbelt	Maryland	United States	20770
9	Nevada Urology Associates	Reno	Nevada	United States	89511
10	Urology Specialists of Oklahoma, Inc.	Tulsa	Oklahoma	United States	74104
11	Urology Clinics of NorthTexas, PA	Dallas	Texas	United States	75231
12	Urology San Antonio Research	San Antonio	Texas	United States	78229

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: NCT00117949
• Other Study ID Numbers: FE200486 CS06
• First Posted: Jul 11, 2005
• Last Update Posted: May 23, 2011
• Last Verified: May 1, 2011

• Keywords provided by , ,: Prostate Cancer; Androgen ablation therapy
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	The patients were followed until they met a pre-defined criterion for insufficient testosterone or prostate-specific antigen (PSA).

Arm/Group Title	Degarelix 40 mg	Degarelix 80 mg	Degarelix 120 mg	Degarelix 160 mg
Arm/Group Description	Degarelix 40 mg (10 mg/mL)	Degarelix 80 mg (20 mg/mL)	Degarelix 120 mg (30 mg/mL)	Degarelix 160 mg (40 mg/mL)
Period Title: Overall Study
STARTED	10	24	24	24
COMPLETED	0	0	0	0
NOT COMPLETED	10	24	24	24

Baseline Characteristics

Arm/Group Title	Degarelix 40 mg	Degarelix 80 mg	Degarelix 120 mg	Degarelix 160 mg	Total
Arm/Group Description	Degarelix 40 mg (10 mg/mL)	Degarelix 80 mg (20 mg/mL)	Degarelix 120 mg (30 mg/mL)	Degarelix 160 mg (40 mg/mL)	Total of all reporting groups
Overall Participants	10	24	24	24	82
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 10%	1 4.2%	2 8.3%	4 16.7%	8 9.8%
>=65 years	9 90%	23 95.8%	22 91.7%	20 83.3%	74 90.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.0 (5.7)	77.5 (6.4)	75.9 (5.8)	74.7 (8.4)	75.6 (6.9)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	10 100%	24 100%	24 100%	24 100%	82 100%
Race/Ethnicity, Customized (participants) [Number]
Oriental/Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Black	2 20%	1 4.2%	2 8.3%	1 4.2%	6 7.3%
Caucasian	5 50%	23 95.8%	15 62.5%	20 83.3%	63 76.8%
Other	3 30%	0 0%	7 29.2%	3 12.5%	13 15.9%
Gleason score (participants) [Number]
Unknown	0 0%	1 4.2%	0 0%	0 0%	1 1.2%
2-4	1 10%	1 4.2%	1 4.2%	0 0%	3 3.7%
5-6	3 30%	14 58.3%	12 50%	13 54.2%	42 51.2%
7-10	6 60%	8 33.3%	11 45.8%	11 45.8%	36 43.9%
Stage of prostate cancer (participants) [Number]
Localized	5 50%	11 45.8%	12 50%	10 41.7%	38 46.3%
Locally advanced	0 0%	6 25%	5 20.8%	5 20.8%	16 19.5%
Metastatic	2 20%	4 16.7%	2 8.3%	2 8.3%	10 12.2%
Not classifiable	3 30%	3 12.5%	5 20.8%	7 29.2%	18 22%
Body mass index (kilogram per square meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter]	26.70 (5.72)	26.61 (3.55)	27.22 (3.16)	26.64 (3.38)	26.70 (5.72)
Serum prostate-specific antigen levels (nanogram per milliliter) [Median (Full Range) ]
Median (Full Range) [nanogram per milliliter]	9.30	13.40	9.10	6.40	9.35
Serum testosterone levels (nanogram per milliliter) [Median (Full Range) ]
Median (Full Range) [nanogram per milliliter]	3.98	4.10	3.96	3.89	3.93
Time since prostate cancer diagnosis (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	851 (1077)	954 (1328)	1609 (1836)	1095 (1385)	1181 (1494)
Weight (kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram]	78.97 (11.73)	81.73 (11.50)	80.77 (12.83)	81.40 (14.36)	81.01 (12.61)

Outcome Measures

1. Primary Outcome

Title	Time to Meet Insufficient Testosterone Response
Description	Figures in the table are Kaplan-Meier estimates of the time to meeting insufficient testosterone response. Insufficient testosterone response was defined as testosterone >1.0 ng/mL at one visit or testosterone 0.5-1.0 at two consecutive visits.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Patients who withdrew without meeting the insufficient testosterone (T) suppression criteria were censored as of the time for last available T measurement prior to discontinuation. For the 40 mg group the 95% confidence interval around the time estimate was non-estimable and no statistical analysis is presented (the estimate was 14 days).

Arm/Group Title	Degarelix 40 mg	Degarelix 80 mg	Degarelix 120 mg	Degarelix 160 mg
Arm/Group Description	Degarelix 40 mg (10 mg/mL)	Degarelix 80 mg (20 mg/mL)	Degarelix 120 mg (30 mg/mL)	Degarelix 160 mg (40 mg/mL)
Measure Participants	10	24	24	24
Median (Full Range) [days]	14	77	98	28

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 40 mg, Degarelix 80 mg, Degarelix 120 mg, Degarelix 160 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Degarelix 80 mg
	Comments	Kaplan-Meier estimates of the time to meet insufficient testosterone (T) response.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median days to insufficient T response
	Estimated Value	84
	Confidence Interval	() 95%; 35 to 112
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Degarelix 120 mg
	Comments	Kaplan-Meier estimates of the time to meet insufficient testosterone (T) response
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median days to insufficient T response
	Estimated Value	98
	Confidence Interval	() 95%; 70 to 126
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Degarelix 160 mg
	Comments	Kaplan-Meier estimates of the time to meet insufficient testosterone (T) response
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median days to insufficient T response
	Estimated Value	35
	Confidence Interval	() 95%; 14 to 98
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to Testosterone Castration (Testosterone ≤0.5 ng/mL).
Description	Time to testosterone castration was calculated as the number of days from dosing to the first scheduled visit when testosterone was less than 0.5 ng/mL. The figures in the table present the number of participants who were castrated after 1, 3, 7, 14, 21, 28, and 42 days.
Time Frame	1, 3, 7, 14, 21, 28, 42 days

Outcome Measure Data

Analysis Population Description

Half participants in the 40 mg group were not castrated and the median was not calculated (no statistical anaylsis was made). Two participants out of 24 in the 80 mg, 1/24 in the 120 mg, and 3/24 in the 160 mg groups were not castrated. For the 160 mg group the 95% CI was non-estimable and no statistical anaylsis was made.

Arm/Group Title	Degarelix 40 mg	Degarelix 80 mg	Degarelix 120 mg	Degarelix 160 mg
Arm/Group Description	Degarelix 40 mg (10 mg/mL)	Degarelix 80 mg (20 mg/mL)	Degarelix 120 mg (30 mg/mL)	Degarelix 160 mg (40 mg/mL)
Measure Participants	10	24	24	24
1 day	1	3	11	6
3 days	3	12	12	14
7 days	1	2	0	1
14 days	0	2	0	0
21 days	0	1	0	0
28 days	0	1	0	0
42 days	0	1	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 40 mg, Degarelix 80 mg, Degarelix 120 mg, Degarelix 160 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Log Rank
	Comments	Participants not castrated were censored as of the days from dosing for the last available observation.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Degarelix 80 mg
	Comments	Kaplan-Meier estimates of the median time to testosterone castration.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median time to castration (days)
	Estimated Value	3
	Confidence Interval	() 95%; 3 to 7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Degarelix 120 mg
	Comments	Kaplan-Meier estimates of the time to testosterone castration.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median time to castration (days)
	Estimated Value	3
	Confidence Interval	() 95%; 1 to 3
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With Sufficient Testosterone Suppression for at Least 84 Days
Description	Sufficient testosterone suppression was defined as not meeting an insufficient testosterone response criterion. Insufficient testosterone response was defined as testosterone >1.0 ng/mL at one visit or testosterone 0.5-1.0 at two consecutive visits.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Degarelix 40 mg	Degarelix 80 mg	Degarelix 120 mg	Degarelix 160 mg
Arm/Group Description	Degarelix 40 mg (10 mg/mL)	Degarelix 80 mg (20 mg/mL)	Degarelix 120 mg (30 mg/mL)	Degarelix 160 mg (40 mg/mL)
Measure Participants	10	24	24	24
Number [participants]	0 0%	9 37.5%	14 58.3%	7 29.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 40 mg
	Comments	Kaplan-Meier estimates of the percentage of participants with sufficient testosterone suppression.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	0
	Confidence Interval	() 95%; 0 to 0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Degarelix 80 mg
	Comments	Kaplan-Meier estimates of the percentage of participants with sufficient testosterone suppression.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	42.7
	Confidence Interval	() 95%; 22 to 63.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Degarelix 120 mg
	Comments	Kaplan-Meier estimates of the percentage of participants with sufficient testosterone suppression.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	61.6
	Confidence Interval	() 95%; 41.8 to 81.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Degarelix 160 mg
	Comments	Kaplan-Meier estimates of the percentage of participants with sufficient testosterone suppression.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	35.6
	Confidence Interval	() 95%; 15.8 to 55.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Number of Participants With Testostestone Serum Levels Below 0.5 ng/mL for at Least 28 Days
Description	The number of participants suppressed for at least 28 days was defined as the estimated "survival probability" at time=Day 28.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Degarelix 40 mg	Degarelix 80 mg	Degarelix 120 mg	Degarelix 160 mg
Arm/Group Description	Degarelix 40 mg (10 mg/mL)	Degarelix 80 mg (20 mg/mL)	Degarelix 120 mg (30 mg/mL)	Degarelix 160 mg (40 mg/mL)
Measure Participants	10	24	24	24
Number [participants]	1 10%	17 70.8%	19 79.2%	13 54.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 40 mg, Degarelix 80 mg, Degarelix 120 mg, Degarelix 160 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.181
	Comments
	Method	Cochran-Armitage Trend Test.
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Degarelix 40 mg
	Comments	Kaplan Meier-estimates of the percentage of participants with testostestone serum levels below 0.5 ng/mL for at least 28 days.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	10
	Confidence Interval	() 95%; 0.3 to 44.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Degarelix 80 mg
	Comments	Kaplan Meier-estimates of the percentage of participants with testostestone serum levels below 0.5 ng/mL for at least 28 days.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	70.8
	Confidence Interval	() 95%; 48.9 to 87.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Degarelix 120 mg
	Comments	Kaplan Meier-estimates of the percentage of participants with testostestone serum levels below 0.5 ng/mL for at least 28 days.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	79.2
	Confidence Interval	() 95%; 57.8 to 92.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Degarelix 160 mg
	Comments	Kaplan Meier-estimates of the percentage of participants with testostestone serum levels below 0.5 ng/mL for at least 28 days.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	54.2
	Confidence Interval	() 95%; 32.8 to 74.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Time to 50% Reduction in Prostate-specific Antigen Levels
Description	The time to 50% prostate-specific antigen (PSA) reduction from baseline was defined as the median number of days from dosing to the first visit where a 50% reduction in PSA level was reached.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Participants who did not achieve the actual level of reduction were censored as of the time from dosing for the last available observation. In the 40 mg group only two participants reached a 50% reduction in PSA and the Kaplan-Meier estimate could not be calculated (ie no statistical analysis is presented for this group).

Arm/Group Title	Degarelix 40 mg	Degarelix 80 mg	Degarelix 120 mg	Degarelix 160 mg
Arm/Group Description	Degarelix 40 mg (10 mg/mL)	Degarelix 80 mg (20 mg/mL)	Degarelix 120 mg (30 mg/mL)	Degarelix 160 mg (40 mg/mL)
Measure Participants	10	24	24	24
Median (Full Range) [days]	10.5	14	14	14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 40 mg, Degarelix 80 mg, Degarelix 120 mg, Degarelix 160 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Degarelix 80 mg
	Comments	Kaplan-Meier estimates of the time (days) to 50% reduction in PSA
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	days
	Estimated Value	14
	Confidence Interval	() 95%; 14 to 28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Degarelix 120 mg
	Comments	Kaplan-Meier estimates of the time (days) to 50% reduction in PSA
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	days
	Estimated Value	14
	Confidence Interval	() 95%; 14 to 28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Degarelix 160 mg
	Comments	Kaplan-Meier estimates of the time (days) to 50% reduction in PSA
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	days
	Estimated Value	28
	Confidence Interval	() 95%; 14 to 41
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Time to 90% Reduction in Prostate-specific Antigen Levels
Description	The time to 90% prostate-specific antigen (PSA) reduction from baseline was defined as the median number of days from dosing to the first visit where a 90% reduction in PSA level was reached.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Participants who did not achieve the actual level of reduction were censored as of the time from dosing for the last available observation. In the 40 mg group only one participant reached a 90% reduction in PSA and the Kaplan-Meier estimate could not be calculated (ie no statistical analysis is presented for this group).

Arm/Group Title	Degarelix 40 mg	Degarelix 80 mg	Degarelix 120 mg	Degarelix 160 mg
Arm/Group Description	Degarelix 40 mg (10 mg/mL)	Degarelix 80 mg (20 mg/mL)	Degarelix 120 mg (30 mg/mL)	Degarelix 160 mg (40 mg/mL)
Measure Participants	10	24	24	24
Median (Full Range) [days]	28	35	35	31.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Degarelix 40 mg, Degarelix 80 mg, Degarelix 120 mg, Degarelix 160 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.926
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Degarelix 80 mg
	Comments	Kaplan-Meier estimates of the time (days) to 90% reduction in PSA.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	days
	Estimated Value	56
	Confidence Interval	() 95%; 35 to 56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Degarelix 120 mg
	Comments	Kaplan-Meier estimates of the time (days) to 90% reduction in PSA.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	days
	Estimated Value	56
	Confidence Interval	() 95%; 35 to 84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Degarelix 160 mg
	Comments	Kaplan-Meier estimates of the time (days) to 90% reduction in PSA.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	days
	Estimated Value	56
	Confidence Interval	() 95%; 35 to 100
	Parameter Dispersion	Type: Value:
	Estimation Comments	The upper confidence interval limit could not be calculated. For technical reasons it has been entered as 100.

7. Secondary Outcome

Title	Liver Function Tests
Description	The number of participants who had abnormal (defined as above upper limit of normal range (ULN)) alanine aminotransferase (ALT) levels, aspartate aminotransferas levels, and bilirubin levels plus the number of participants who had ALT increases >3x ULN and ALT increases >3x ULN with concurrently increased bilirubin >1.5 ULN.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Degarelix 40 mg	Degarelix 80 mg	Degarelix 120 mg	Degarelix 160 mg
Arm/Group Description	Degarelix 40 mg (10 mg/mL)	Degarelix 80 mg (20 mg/mL)	Degarelix 120 mg (30 mg/mL)	Degarelix 160 mg (40 mg/mL)
Measure Participants	10	24	24	24
Abnormal alanine aminotransferase (ALAT)	0 0%	3 12.5%	3 12.5%	6 25%
Abnormal aspartate aminotransferase	1 10%	11 45.8%	13 54.2%	9 37.5%
Abnormal bilirubin	2 20%	0 0%	2 8.3%	2 8.3%
ALAT >3x upper limit of normal (ULN)	0 0%	1 4.2%	0 0%	0 0%
ALAT >3x ULN, bilirubin >1.5x ULN	0 0%	0 0%	0 0%	0 0%

Adverse Events

Arm/Group Title	Degarelix 40 mg		Degarelix 80 mg		Degarelix 120 mg		Degarelix 160 mg
Arm/Group Description	Degarelix 40 mg (10 mg/mL)		Degarelix 80 mg (20 mg/mL)		Degarelix 120 mg (30 mg/mL)		Degarelix 160 mg (40 mg/mL)
All Cause Mortality
	Degarelix 40 mg		Degarelix 80 mg		Degarelix 120 mg		Degarelix 160 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Degarelix 40 mg		Degarelix 80 mg		Degarelix 120 mg		Degarelix 160 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/ (NaN)		1/ (NaN)		1/ (NaN)		0/ (NaN)
Gastrointestinal disorders
Small intestinal obstruction	0/10 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0
General disorders
Chest pain	0/10 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0
Other (Not Including Serious) Adverse Events
	Degarelix 40 mg		Degarelix 80 mg		Degarelix 120 mg		Degarelix 160 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/ (NaN)		18/ (NaN)		20/ (NaN)		13/ (NaN)
Blood and lymphatic system disorders
Anaemia	0/10 (0%)	0	0/24 (0%)	0	3/24 (12.5%)	4	0/24 (0%)	0
Eye disorders
Diabetic retinopathy	1/10 (10%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/10 (0%)	0	1/24 (4.2%)	1	2/24 (8.3%)	2	0/24 (0%)	0
Constipation	0/10 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0
Haemorrhoids	0/10 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0
Inguinal hernia	0/10 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0	0/24 (0%)	0
General disorders
Injection site pain	0/10 (0%)	0	2/24 (8.3%)	2	3/24 (12.5%)	4	1/24 (4.2%)	1
Fatigue	1/10 (10%)	1	2/24 (8.3%)	2	0/24 (0%)	0	2/24 (8.3%)	2
Injection site pruritus	0/10 (0%)	0	2/24 (8.3%)	2	1/24 (4.2%)	1	0/24 (0%)	0
Chest pain	0/10 (0%)	0	2/24 (8.3%)	4	0/24 (0%)	0	0/24 (0%)	0
Infections and infestations
Nasopharyngitis	0/10 (0%)	0	2/24 (8.3%)	2	3/24 (12.5%)	3	1/24 (4.2%)	1
Investigations
Alanine aminotransferase increased	0/10 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0	0/24 (0%)	0
Aspartate aminotransferase increased	0/10 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0	0/24 (0%)	0
Breath sounds abnormal	1/10 (10%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/10 (10%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0
Osteoarthritis	1/10 (10%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0
Nervous system disorders
Dizziness	1/10 (10%)	1	2/24 (8.3%)	2	2/24 (8.3%)	2	1/24 (4.2%)	1
Headache	1/10 (10%)	1	1/24 (4.2%)	1	2/24 (8.3%)	2	0/24 (0%)	0
Psychiatric disorders
Libido decreased	0/10 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2
Renal and urinary disorders
Dysuria	0/10 (0%)	0	2/24 (8.3%)	2	1/24 (4.2%)	1	1/24 (4.2%)	1
Urinary retention	0/10 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0	0/24 (0%)	0
Urine flow decreased	1/10 (10%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/10 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	0/10 (0%)	0	2/24 (8.3%)	3	0/24 (0%)	0	0/24 (0%)	0
Vascular disorders
Hot flush	2/10 (20%)	2	12/24 (50%)	12	5/24 (20.8%)	6	5/24 (20.8%)	5
Hypertension	0/10 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

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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.