Trial Outcomes & Findings for A Trial of Degarelix in Patients With Prostate Cancer (NCT NCT00946920)

Last Updated: 2014-06-02

Results Overview

This co-primary outcome measure was used to demonstrate that degarelix is effective with respect to achieving and maintaining testosterone suppression to castrate levels, evaluated as the proportion of patients with testosterone suppression ≤0.5 ng/mL from Day 28 to Day 364.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

859 participants

Primary outcome timeframe

From Day 28 to Day 364

Results posted on

2014-06-02

Participant Flow

Subjects who met the eligibility criteria were randomized to degarelix or goserelin acetate treatment in a 2:1-ratio. 859 subjects were randomized but 11 subjects did not receive any treatment.

Participant milestones

Participant milestones
Measure	Degarelix 240 mg/480 mg Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).	Goserelin Acetate Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).
Overall Study STARTED	565	283
Overall Study Full Analysis Set (FAS)	565	282
Overall Study COMPLETED	455	239
Overall Study NOT COMPLETED	110	44

Reasons for withdrawal

Reasons for withdrawal
Measure	Degarelix 240 mg/480 mg Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).	Goserelin Acetate Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).
Overall Study Withdrawal by Subject	28	15
Overall Study Lost to Follow-up	2	2
Overall Study Physician Decision	5	2
Overall Study Adverse Event	41	14
Overall Study Protocol Violation	16	8
Overall Study Miscellaneous reasons	18	3

Baseline Characteristics

A Trial of Degarelix in Patients With Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Degarelix 240 mg/480 mg n=565 Participants Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).	Goserelin Acetate n=282 Participants Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).	Total n=847 Participants Total of all reporting groups
Age, Continuous	71.9 years STANDARD_DEVIATION 8.3 • n=5 Participants	71.1 years STANDARD_DEVIATION 7.9 • n=7 Participants	71.6 years STANDARD_DEVIATION 8.2 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	565 Participants n=5 Participants	282 Participants n=7 Participants	847 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	45 Participants n=5 Participants	25 Participants n=7 Participants	70 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	41 Participants n=5 Participants	16 Participants n=7 Participants	57 Participants n=5 Participants
Race (NIH/OMB) White	475 Participants n=5 Participants	239 Participants n=7 Participants	714 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Median Baseline Serum Testosterone Levels (ng/mL)	4.52 ng/mL n=5 Participants	4.62 ng/mL n=7 Participants	4.54 ng/mL n=5 Participants
Median Baseline Serum Prostate-specific Antigen Levels (ng/mL)	19.0 ng/mL n=5 Participants	19.1 ng/mL n=7 Participants	19.0 ng/mL n=5 Participants
Baseline Short Form-36 (SF-36) Total Scores	49.7 units on a scale STANDARD_DEVIATION 11.5 • n=5 Participants	50.2 units on a scale STANDARD_DEVIATION 11.4 • n=7 Participants	49.9 units on a scale STANDARD_DEVIATION 11.4 • n=5 Participants
Baseline Total International Prostate Symptom Scores (IPSS)	11.8 units on a scale STANDARD_DEVIATION 7.93 • n=5 Participants	11.6 units on a scale STANDARD_DEVIATION 8.02 • n=7 Participants	11.7 units on a scale STANDARD_DEVIATION 7.96 • n=5 Participants

PRIMARY outcome

Timeframe: From Day 28 to Day 364

Population: FAS.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/480 mg n=565 Participants Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).	Goserelin Acetate Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).
Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) With Degarelix	90.0 percentage of participants Interval 87.0 to 92.3	—

PRIMARY outcome

Timeframe: Day 3 to Day 364

Population: FAS.

This co-primary outcome measure was used to establish non-inferiority of degarelix as compared to goserelin with regard to achieving and maintaining testosterone suppression at castrate levels (≤0.5 ng/mL) from Day 3 to Day 364, using a non-inferiority margin of 5 percentage points.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/480 mg n=565 Participants Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).	Goserelin Acetate n=282 Participants Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).
Difference in Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) Between Degarelix and Goserelin	85.0 percentage of participants Interval 81.6 to 87.8	5.3 percentage of participants Interval 3.1 to 8.4

SECONDARY outcome

Timeframe: Baseline and after 1, 2, 3, 6 and 13 months

Population: FAS.

Median testosterone levels are presented as absolute values at Baseline (in Baseline measures) and after 1, 2, 3, 6 and 13 months (below). One treatment month equals 28 days.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/480 mg n=565 Participants Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).	Goserelin Acetate n=282 Participants Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).
Serum Levels of Testosterone Over Time Month 1	0.10 ng/mL Interval 0.015 to 3.85	0.16 ng/mL Interval 0.04 to 1.77
Serum Levels of Testosterone Over Time Month 2	0.09 ng/mL Interval 0.015 to 0.41	0.10 ng/mL Interval 0.015 to 0.5
Serum Levels of Testosterone Over Time Month 3	0.09 ng/mL Interval 0.015 to 3.24	0.09 ng/mL Interval 0.015 to 5.4
Serum Levels of Testosterone Over Time Month 6	0.09 ng/mL Interval 0.015 to 1.57	0.09 ng/mL Interval 0.015 to 0.32
Serum Levels of Testosterone Over Time Month 13	0.11 ng/mL Interval 0.015 to 4.19	0.09 ng/mL Interval 0.015 to 0.95

SECONDARY outcome

Timeframe: Baseline and after 1, 2, 3, 6 and 13 months

Population: FAS.

Serum PSA levels are presented as mean percent change from Baseline (in Baseline measures) after 1, 2, 3, 6 and 13 months. One treatment month equals 28 days.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/480 mg n=565 Participants Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).	Goserelin Acetate n=282 Participants Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).
Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time Month 6	-90 percent change Standard Deviation 30.5	-91 percent change Standard Deviation 18.2
Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time Month 1	-77 percent change Standard Deviation 23.7	-57 percent change Standard Deviation 45.7
Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time Month 2	-89 percent change Standard Deviation 12.6	-86 percent change Standard Deviation 18.1
Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time Month 3	-90 percent change Standard Deviation 15.4	-86 percent change Standard Deviation 58.6
Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time Month 13	-82 percent change Standard Deviation 104	-77 percent change Standard Deviation 146

SECONDARY outcome

Timeframe: At baseline, 10 months and 13 months

Population: FAS.

The SF-36 is a multi-purpose, short-form health survey with only 36 questions and with a minimum score of 0 and a maximum score of 100. The higher score the better health. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. The SF-36 has proven useful in surveys of general and specific populations, comparing the relative burden of diseases, and in differentiating the health benefits produced by a wide range of different treatments.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/480 mg n=565 Participants Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).	Goserelin Acetate n=282 Participants Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).
Change in Health-related Quality of Life (HRQoL), as Measured by Short Form-36 (SF-36) Score at Month 10 and Month 13 Compared to Baseline Month 10	0.52 units on a scale Standard Deviation 11.1	0.27 units on a scale Standard Deviation 10.6
Change in Health-related Quality of Life (HRQoL), as Measured by Short Form-36 (SF-36) Score at Month 10 and Month 13 Compared to Baseline Month 13	0.18 units on a scale Standard Deviation 10.9	-0.87 units on a scale Standard Deviation 9.76

SECONDARY outcome

Timeframe: At baseline, 1 month, 4 months, 7 months and 13 months

Population: FAS.

IPSS is used to assess severity of lower urinary tract symptoms and to monitor the progress of symptoms once treatment has been initiated. It contains 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5 (i.e. the minimum total score is 0 and the maximum is 35). A score of "0" corresponds to a response of "not at all" for the first six symptoms and "none" for nocturia, and a score of 5 corresponds to a response of "almost always" for the first six symptoms and "5 times or more" for nocturia.

Outcome measures

Outcome measures
Measure	Degarelix 240 mg/480 mg n=565 Participants Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).	Goserelin Acetate n=282 Participants Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).
Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline Month 1	-1.06 units on a scale Standard Deviation 6.27	-0.21 units on a scale Standard Deviation 6.22
Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline Month 4	-2.31 units on a scale Standard Deviation 6.65	-1.74 units on a scale Standard Deviation 6.16
Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline Month 7	-2.47 units on a scale Standard Deviation 6.94	-2.45 units on a scale Standard Deviation 6.80
Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline Month 13	-2.04 units on a scale Standard Deviation 7.28	-1.52 units on a scale Standard Deviation 6.25

Adverse Events

Degarelix 240 mg/480 mg

Serious events: 58 serious events

Other events: 336 other events

Deaths: 0 deaths

Goserelin Acetate

Serious events: 33 serious events

Other events: 125 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Degarelix 240 mg/480 mg n=565 participants at risk Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).	Goserelin Acetate n=283 participants at risk Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).
Vascular disorders Hot flush	28.3% 160/565 • Number of events 175 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.	26.9% 76/283 • Number of events 80 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.
General disorders Injection site pain	30.6% 173/565 • Number of events 429 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.	1.4% 4/283 • Number of events 4 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.
General disorders Injection site erythema	21.6% 122/565 • Number of events 323 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.	0.00% 0/283 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.
General disorders Injection site nodule	9.0% 51/565 • Number of events 112 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.	0.00% 0/283 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.
Investigations Weight increased	4.6% 26/565 • Number of events 26 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.	8.5% 24/283 • Number of events 24 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.
Infections and infestations Urinary tract infection	4.2% 24/565 • Number of events 30 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.	6.4% 18/283 • Number of events 24 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.
General disorders Fatigue	4.6% 26/565 • Number of events 28 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.	5.3% 15/283 • Number of events 15 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.
Musculoskeletal and connective tissue disorders Back pain	3.4% 19/565 • Number of events 21 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.	7.4% 21/283 • Number of events 27 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.
Vascular disorders Hypertension	3.9% 22/565 • Number of events 24 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.	6.4% 18/283 • Number of events 21 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.
General disorders Pyrexia	5.5% 31/565 • Number of events 40 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.	2.5% 7/283 • Number of events 7 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.
General disorders Injection site swelling	6.0% 34/565 • Number of events 102 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.	0.00% 0/283 • Adverse events were recorded from signed informed consent until the end-of-trial visit, Day 364 (Month 13). Adverse events were evaluated at each visit.

Additional Information

Clinical Development Support

Ferring Pharmaceuticals

Email: [email protected]

Results disclosure agreements

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