Trial Outcomes & Findings for A Long-term Extension Study Evaluating a One-Month Dosing Regimen of Degarelix in Prostate Cancer Requiring Androgen Ablation Therapy (NCT NCT00451958)

NCT ID: NCT00451958

Last Updated: 2013-03-21

Results Overview

This outcome measure included incidence of markedly abnormal changes in blood pressure (systolic and diastolic), pulse, and body weight. The table presents the number of participants with normal baseline (from main CS21 study, NCT00295750) and at least one post-baseline markedly abnormal value during CS21A.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

386 participants

Primary outcome timeframe

Up to 4 years of treatment

Results posted on

2013-03-21

Participant Flow

All participants who completed the CS21 study (NCT00295750) were eligible to enrol into the CS21A extension study. Since the number of participants who completed this long-term study was low, no firm conclusions can be drawn from the results.

Initially, participants treated with degarelix during CS21 continued to treatment and patients who received treatment with leuprolide during CS21 were re-randomised to one of the two degarelix treatment regimens. Following a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg for the rest of the study.

Participant milestones

Participant milestones
Measure	Degarelix 80 mg / Degarelix 80 mg The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 of the CS21 study (NCT00295750) as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the CS21 study and the current CS21A study.	Degarelix 160 mg / Degarelix 160 mg The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 of the CS21 study (NCT00295750) as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the CS21 study and the current CS21A study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 80 mg During the main CS21 study (NCT00295750), leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 160 mg During the main CS21 study (NCT00295750), leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg During the main CS21 study (NCT00295750), leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. When the main CS21 study was completed these patients were switched to treatment with degarelix 80 mg or 160 mg in the CS21A study.
CS21 (NCT00295750) STARTED	210	206	0	0	204
CS21 (NCT00295750) COMPLETED	169	163	0	0	172
CS21 (NCT00295750) NOT COMPLETED	41	43	0	0	32
CS21A (NCT00451958) STARTED	125	126	69	66	0
CS21A (NCT00451958) COMPLETED	60	49	27	27	0
CS21A (NCT00451958) NOT COMPLETED	65	77	42	39	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Degarelix 80 mg / Degarelix 80 mg The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 of the CS21 study (NCT00295750) as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the CS21 study and the current CS21A study.	Degarelix 160 mg / Degarelix 160 mg The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 of the CS21 study (NCT00295750) as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the CS21 study and the current CS21A study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 80 mg During the main CS21 study (NCT00295750), leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 160 mg During the main CS21 study (NCT00295750), leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.
CS21A (NCT00451958) Adverse Event	21	34	14	17
CS21A (NCT00451958) Lost to Follow-up	6	5	1	1
CS21A (NCT00451958) Protocol Violation	1	3	2	0
CS21A (NCT00451958) Physician Decision	2	4	4	4
CS21A (NCT00451958) Withdrawal by Subject	7	4	4	3
CS21A (NCT00451958) Miscellaneous reasons	28	27	17	14

Baseline Characteristics

A Long-term Extension Study Evaluating a One-Month Dosing Regimen of Degarelix in Prostate Cancer Requiring Androgen Ablation Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Degarelix 80 mg / Degarelix 80 mg n=125 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the study.	Degarelix 160 mg / Degarelix 160 mg n=126 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 80 mg n=69 Participants During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 160 mg n=65 Participants During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Total n=385 Participants Total of all reporting groups
Age Continuous	70.1 years STANDARD_DEVIATION 7.62 • n=5 Participants	71.1 years STANDARD_DEVIATION 8.25 • n=7 Participants	72.4 years STANDARD_DEVIATION 9.46 • n=5 Participants	71.4 years STANDARD_DEVIATION 8.24 • n=4 Participants	71.1 years STANDARD_DEVIATION 8.29 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	125 Participants n=5 Participants	126 Participants n=7 Participants	69 Participants n=5 Participants	65 Participants n=4 Participants	385 Participants n=21 Participants
Region of Enrollment United States	12 participants n=5 Participants	14 participants n=7 Participants	13 participants n=5 Participants	9 participants n=4 Participants	48 participants n=21 Participants
Region of Enrollment Hungary	7 participants n=5 Participants	9 participants n=7 Participants	5 participants n=5 Participants	5 participants n=4 Participants	26 participants n=21 Participants
Region of Enrollment Czech Republic	11 participants n=5 Participants	12 participants n=7 Participants	6 participants n=5 Participants	8 participants n=4 Participants	37 participants n=21 Participants
Region of Enrollment Mexico	15 participants n=5 Participants	17 participants n=7 Participants	10 participants n=5 Participants	7 participants n=4 Participants	49 participants n=21 Participants
Region of Enrollment Canada	4 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	4 participants n=4 Participants	18 participants n=21 Participants
Region of Enrollment Ukraine	11 participants n=5 Participants	10 participants n=7 Participants	7 participants n=5 Participants	3 participants n=4 Participants	31 participants n=21 Participants
Region of Enrollment Romania	36 participants n=5 Participants	39 participants n=7 Participants	16 participants n=5 Participants	15 participants n=4 Participants	106 participants n=21 Participants
Region of Enrollment Russian Federation	26 participants n=5 Participants	19 participants n=7 Participants	6 participants n=5 Participants	13 participants n=4 Participants	64 participants n=21 Participants
Region of Enrollment Netherlands	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	3 participants n=21 Participants
Region of Enrollment Germany	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Region of Enrollment United Kingdom	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants
Body Weight	78.4 kilogram STANDARD_DEVIATION 12.6 • n=5 Participants	79.2 kilogram STANDARD_DEVIATION 13.4 • n=7 Participants	78.7 kilogram STANDARD_DEVIATION 11.3 • n=5 Participants	80.0 kilogram STANDARD_DEVIATION 12.1 • n=4 Participants	79.0 kilogram STANDARD_DEVIATION 12.5 • n=21 Participants
Body Mass Index	26.4 kilogram per square meter STANDARD_DEVIATION 3.92 • n=5 Participants	26.9 kilogram per square meter STANDARD_DEVIATION 3.79 • n=7 Participants	26.9 kilogram per square meter STANDARD_DEVIATION 3.94 • n=5 Participants	27.1 kilogram per square meter STANDARD_DEVIATION 3.67 • n=4 Participants	26.8 kilogram per square meter STANDARD_DEVIATION 3.84 • n=21 Participants
Gleason Score Gleason Score 2-4	15 participants n=5 Participants	17 participants n=7 Participants	8 participants n=5 Participants	11 participants n=4 Participants	51 participants n=21 Participants
Gleason Score Gleason Score 5-6	37 participants n=5 Participants	44 participants n=7 Participants	25 participants n=5 Participants	18 participants n=4 Participants	124 participants n=21 Participants
Gleason Score Gleason Score 7-10	73 participants n=5 Participants	63 participants n=7 Participants	36 participants n=5 Participants	36 participants n=4 Participants	208 participants n=21 Participants
Stage of Prostate Cancer Localised	39 participants n=5 Participants	36 participants n=7 Participants	20 participants n=5 Participants	19 participants n=4 Participants	114 participants n=21 Participants
Stage of Prostate Cancer Locally advanced	46 participants n=5 Participants	44 participants n=7 Participants	18 participants n=5 Participants	24 participants n=4 Participants	132 participants n=21 Participants
Stage of Prostate Cancer Metastatic	23 participants n=5 Participants	22 participants n=7 Participants	21 participants n=5 Participants	9 participants n=4 Participants	75 participants n=21 Participants
Stage of Prostate Cancer Not classifiable	17 participants n=5 Participants	24 participants n=7 Participants	10 participants n=5 Participants	13 participants n=4 Participants	64 participants n=21 Participants
Serum Testosterone Levels	4.63 nanograms per milliliter n=5 Participants	4.02 nanograms per milliliter n=7 Participants	4.32 nanograms per milliliter n=5 Participants	3.51 nanograms per milliliter n=4 Participants	4.23 nanograms per milliliter n=21 Participants
Serum Prostate-Specific Antigen (PSA) Levels	22.2 nanograms per milliliter n=5 Participants	22.5 nanograms per milliliter n=7 Participants	25.5 nanograms per milliliter n=5 Participants	14.0 nanograms per milliliter n=4 Participants	21.0 nanograms per milliliter n=21 Participants

PRIMARY outcome

Timeframe: Up to 4 years of treatment

Population: The analysis population comprised all participants who were enrolled in the CS21A study and who received at least one dose of degarelix during the study period.

Outcome measures

Outcome measures
Measure	Degarelix 80 mg / Degarelix 80 mg n=125 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the study.	Degarelix 160 mg / Degarelix 160 mg n=126 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 80 mg n=69 Participants During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 160 mg n=66 Participants During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.
Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight Systolic blood pressure >=180 and increase >=20	7 participants	13 participants	7 participants	4 participants
Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight Diastolic blood pressure <=50 and decrease >=15	3 participants	6 participants	3 participants	6 participants
Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight Diastolic blood pressure >=105 and increase >=15	3 participants	6 participants	4 participants	0 participants
Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight Systolic blood pressure <=90 and decrease >=20	4 participants	4 participants	5 participants	3 participants
Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight Heart rate <=50 and decrease >=15	4 participants	3 participants	7 participants	2 participants
Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight Heart rate >=120 and increase >=15	1 participants	1 participants	1 participants	3 participants
Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight Body weight decrease of >=7 percent	15 participants	24 participants	21 participants	8 participants
Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight Body weight increase of >=7 percent	25 participants	14 participants	4 participants	5 participants

PRIMARY outcome

Timeframe: Up to 4 years of treatment

Population: The analysis population comprised all participants who were enrolled in the CS21A study and who received at least one dose of degarelix during the study period.

This outcome measure included incidence of markedly abnormal changes in safety laboratory values. The table presents the number of participants with normal baseline (from main CS21 trial, NCT00295750) and at least one post-baseline markedly abnormal value during CS21A. Only the laboratory variables that had at least five percentages of participants in either group with abnormal value are presented, more variables were included in the study. ULN=Upper limit of normal.

Outcome measures

Outcome measures
Measure	Degarelix 80 mg / Degarelix 80 mg n=125 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the study.	Degarelix 160 mg / Degarelix 160 mg n=126 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 80 mg n=69 Participants During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 160 mg n=65 Participants During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.
Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables S-Potassium (mmol/L) >=5.8	11 participants	9 participants	6 participants	5 participants
Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables S-Alanine aminotransferase (IU/L) >3xULN	1 participants	6 participants	1 participants	0 participants
Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables S-Alkaline phosphatase (IU/L) >3xULN+25% increase	4 participants	5 participants	4 participants	2 participants
Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables S-Creatinine (µmol/L) >=177	12 participants	7 participants	5 participants	2 participants
Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables S-Urea nitrogen (mmol/L) >=10.7	6 participants	9 participants	5 participants	5 participants
Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables B-Haematocrit (Ratio) <=0.37	40 participants	47 participants	22 participants	17 participants
Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables B-Haemoglobin (g/L) <=115	12 participants	20 participants	9 participants	6 participants
Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables B-Red blood cell count (10^12/L) <=3.5	10 participants	15 participants	5 participants	3 participants
Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables B-Eosinophils (%) >=10	6 participants	7 participants	1 participants	1 participants
Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables B-Lymphocytes (%) <=10	8 participants	9 participants	10 participants	5 participants

SECONDARY outcome

Timeframe: Until all participants have received at least 5 years of treatment and at a frequency of every 3 months

Population: CS21 ITT analysis set i.e. all participants who received at least one dose of degarelix or leuprolide during the mail study (CS21).

PSA progression was defined as two consecutive increases of 50%, and at least 5 ng/mL, compared to nadir (obtained in either CS21, NCT00295750, or CS21A). The figures below present the percentage of participants with no PSA progression at each of the selected time points (there were more time points in the study) along with corresponding 95% confidence intervals (CI).

Outcome measures

Outcome measures
Measure	Degarelix 80 mg / Degarelix 80 mg n=207 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the study.	Degarelix 160 mg / Degarelix 160 mg n=202 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 80 mg n=69 Participants During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 160 mg n=132 Participants During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.
Percentage of Participants With no Prostate-specific Antigen (PSA) Progression Day 28	100 percentage of participants Interval 100.0 to 100.0	99.5 percentage of participants Interval 96.5 to 99.9	98.6 percentage of participants Interval 90.2 to 99.8	100 percentage of participants Interval 100.0 to 100.0
Percentage of Participants With no Prostate-specific Antigen (PSA) Progression Day 364	91.1 percentage of participants Interval 85.9 to 94.5	85.8 percentage of participants Interval 79.8 to 90.1	82.6 percentage of participants Interval 71.4 to 89.7	87.9 percentage of participants Interval 80.4 to 92.7
Percentage of Participants With no Prostate-specific Antigen (PSA) Progression Day 1960	61.0 percentage of participants Interval 50.9 to 69.7	58.7 percentage of participants Interval 48.7 to 67.4	50.7 percentage of participants Interval 36.3 to 63.4	73.8 percentage of participants Interval 60.9 to 83.0

SECONDARY outcome

Timeframe: Until all participants have received at least 5 years of treatment and at a frequency of every 6 months

Population: CS21 ITT analysis set i.e. all participants who received at least one dose of degarelix or leuprolide during the mail CS21 study (NCT00295750).

The results below present the percentage of participants of having testosterone \<=0.5 ng/mL at each of the selected time points (there were more time points in the study) from Day 28 in CS21 (NCT00295750) until the end of the CS21A study. In all treatment groups approximately 3% per year of the participants had at least one testosterone \>0.5 ng/mL during the study.

Outcome measures

Outcome measures
Measure	Degarelix 80 mg / Degarelix 80 mg n=206 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the study.	Degarelix 160 mg / Degarelix 160 mg n=197 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 80 mg n=69 Participants During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 160 mg n=128 Participants During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.
Percentage of Participants With Testosterone Level Maintained at <=0.5 ng/mL From Day 28 in CS21 and Onwards Day 84	99.5 percentage Interval 96.5 to 99.9	100 percentage Interval 100.0 to 100.0	98.6 percentage Interval 90.2 to 99.8	97.6 percentage Interval 92.7 to 99.2
Percentage of Participants With Testosterone Level Maintained at <=0.5 ng/mL From Day 28 in CS21 and Onwards Day 364	97.2 percentage Interval 93.5 to 98.8	98.3 percentage Interval 94.8 to 99.4	97. percentage Interval 88.9 to 99.3	96.0 percentage Interval 90.5 to 98.3
Percentage of Participants With Testosterone Level Maintained at <=0.5 ng/mL From Day 28 in CS21 and Onwards Day 1876	82.0 percentage Interval 72.7 to 88.4	87.7 percentage Interval 78.0 to 93.3	84.1 percentage Interval 70.2 to 91.9	88.4 percentage Interval 75.5 to 94.7

SECONDARY outcome

Timeframe: From time of switch to Day 56

Population: All participants who received leuprolide in the main CS21 study (NCT00295750) and were switched over to degarelix in the CS21A extension study.

Outcome measures

Outcome measures
Measure	Degarelix 80 mg / Degarelix 80 mg n=69 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the study.	Degarelix 160 mg / Degarelix 160 mg n=64 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 80 mg During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 160 mg During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.
Serum Levels of Testosterone From the Time of Switch From Leuprolide to Degarelix up to Day 56 Baseline	0.076 ng/mL Interval 0.015 to 1.36	0.074 ng/mL Interval 0.015 to 0.229	—	—
Serum Levels of Testosterone From the Time of Switch From Leuprolide to Degarelix up to Day 56 Day 3	0.084 ng/mL Interval 0.015 to 0.23	0.068 ng/mL Interval 0.015 to 0.19	—	—
Serum Levels of Testosterone From the Time of Switch From Leuprolide to Degarelix up to Day 56 Day 7	0.076 ng/mL Interval 0.015 to 0.22	0.066 ng/mL Interval 0.015 to 0.16	—	—
Serum Levels of Testosterone From the Time of Switch From Leuprolide to Degarelix up to Day 56 Day 14	0.085 ng/mL Interval 0.015 to 0.24	0.073 ng/mL Interval 0.015 to 0.27	—	—
Serum Levels of Testosterone From the Time of Switch From Leuprolide to Degarelix up to Day 56 Day 28	0.074 ng/mL Interval 0.015 to 0.21	0.074 ng/mL Interval 0.015 to 0.19	—	—
Serum Levels of Testosterone From the Time of Switch From Leuprolide to Degarelix up to Day 56 Day 56	0.080 ng/mL Interval 0.015 to 0.22	0.077 ng/mL Interval 0.015 to 0.16	—	—

SECONDARY outcome

Timeframe: From time of switch to Day 56

Population: All participants who received leuprolide in the main CS21 study (NCT00295750) and were switched over to degarelix in the CS21A extension study.

Outcome measures

Outcome measures
Measure	Degarelix 80 mg / Degarelix 80 mg n=69 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the study.	Degarelix 160 mg / Degarelix 160 mg n=65 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 80 mg During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 160 mg During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.
Serum Levels of PSA From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 3	0.4 ng/mL Interval 0.0 to 754.0	0.3 ng/mL Interval 0.0 to 1059.0	—	—
Serum Levels of PSA From the Time of Switch From Leuprolide to Degarelix to Day 56 Baseline	0.4 ng/mL Interval 0.0 to 2938.0	0.4 ng/mL Interval 0.0 to 1096.0	—	—
Serum Levels of PSA From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 7	0.35 ng/mL Interval 0.0 to 724.0	0.4 ng/mL Interval 0.0 to 1422.0	—	—
Serum Levels of PSA From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 14	0.4 ng/mL Interval 0.0 to 671.0	0.3 ng/mL Interval 0.0 to 1567.0	—	—
Serum Levels of PSA From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 28	0.4 ng/mL Interval 0.0 to 441.0	0.5 ng/mL Interval 0.0 to 2008.0	—	—
Serum Levels of PSA From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 56	0.35 ng/mL Interval 0.0 to 620.0	0.4 ng/mL Interval 0.0 to 1926.0	—	—

SECONDARY outcome

Timeframe: From time of switch to Day 56

Population: All participants who received leuprolide in the main CS21 study (NCT00295750) and were switched over to degarelix in the CS21A extension study.

Outcome measures

Outcome measures
Measure	Degarelix 80 mg / Degarelix 80 mg n=69 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the study.	Degarelix 160 mg / Degarelix 160 mg n=65 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 80 mg During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 160 mg During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.
Serum Levels of Luteinizing Hormone (LH) From the Time of Switch From Leuprolide to Degarelix to Day 56 Baseline	0.035 International units/Liter (IU/L) Interval 0.035 to 1.12	0.035 International units/Liter (IU/L) Interval 0.035 to 0.4	—	—
Serum Levels of Luteinizing Hormone (LH) From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 3	0.035 International units/Liter (IU/L) Interval 0.035 to 0.11	0.035 International units/Liter (IU/L) Interval 0.035 to 0.12	—	—
Serum Levels of Luteinizing Hormone (LH) From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 7	0.035 International units/Liter (IU/L) Interval 0.035 to 0.11	0.035 International units/Liter (IU/L) Interval 0.035 to 0.08	—	—
Serum Levels of Luteinizing Hormone (LH) From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 14	0.035 International units/Liter (IU/L) Interval 0.035 to 0.47	0.035 International units/Liter (IU/L) Interval 0.035 to 0.12	—	—
Serum Levels of Luteinizing Hormone (LH) From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 28	0.035 International units/Liter (IU/L) Interval 0.035 to 0.16	0.035 International units/Liter (IU/L) Interval 0.035 to 0.19	—	—
Serum Levels of Luteinizing Hormone (LH) From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 56	0.035 International units/Liter (IU/L) Interval 0.035 to 0.17	0.035 International units/Liter (IU/L) Interval 0.035 to 0.22	—	—

SECONDARY outcome

Timeframe: From time of switch to Day 56

Population: All participants who received leuprolide in the main CS21 study (NCT00295750) and were switched over to degarelix in the CS21A extension study.

Outcome measures

Outcome measures
Measure	Degarelix 80 mg / Degarelix 80 mg n=69 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the study.	Degarelix 160 mg / Degarelix 160 mg n=65 Participants The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 80 mg During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.	Leuprolide 7.5 mg / Degarelix 160 mg During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year. Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study. Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.
Serum Levels of Follicle Stimulating Hormone (FSH) From the Time of Switch From Leuprolide to Degarelix to Day 56 Baseline	4.8 International units/Liter (IU/L) Interval 1.2 to 15.8	4.4 International units/Liter (IU/L) Interval 1.5 to 12.2	—	—
Serum Levels of Follicle Stimulating Hormone (FSH) From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 3	2.7 International units/Liter (IU/L) Interval 0.8 to 11.1	2.8 International units/Liter (IU/L) Interval 0.5 to 7.6	—	—
Serum Levels of Follicle Stimulating Hormone (FSH) From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 7	2.6 International units/Liter (IU/L) Interval 0.7 to 11.8	2.6 International units/Liter (IU/L) Interval 0.4 to 6.9	—	—
Serum Levels of Follicle Stimulating Hormone (FSH) From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 14	2.2 International units/Liter (IU/L) Interval 0.15 to 7.9	2.3 International units/Liter (IU/L) Interval 0.15 to 8.3	—	—
Serum Levels of Follicle Stimulating Hormone (FSH) From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 28	1.8 International units/Liter (IU/L) Interval 0.15 to 7.6	1.7 International units/Liter (IU/L) Interval 0.15 to 6.7	—	—
Serum Levels of Follicle Stimulating Hormone (FSH) From the Time of Switch From Leuprolide to Degarelix to Day 56 Day 56	1.3 International units/Liter (IU/L) Interval 0.15 to 6.7	1.55 International units/Liter (IU/L) Interval 0.15 to 5.6	—	—

Adverse Events

Degarelix 80 mg / Degarelix 80 mg

Serious events: 43 serious events

Other events: 181 other events

Deaths: 0 deaths

Degarelix 160 mg / Degarelix 160 mg

Serious events: 60 serious events

Other events: 177 other events

Deaths: 0 deaths

Leuprolide 7.5 mg / Degarelix 80 mg

Serious events: 23 serious events

Other events: 63 other events

Deaths: 0 deaths

Leuprolide 7.5 mg / Degarelix 160 mg

Serious events: 22 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Development Support

Ferring Pharmaceuticals

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER