Trial Outcomes & Findings for Study to Assess the Efficacy of Brachytherapy With or Without Hormone Therapy, Using Triptorelin 22.5mg in Patients With Recurrence of Prostate Cancer (NCT NCT01374087)

Last Updated: 2019-09-18

Results Overview

BFFS was determined by a prostate-specific antigen (PSA) increase of 2 nanograms per millilitre (ng/mL) or more in comparison with the pre-study nadir PSA and confirmed in the course of follow-up by a second value 3 weeks later or longer over the 5 year follow-up. Time to BFFS was defined from treatment initiation to the first time when PSA increase of 2 ng/mL was observed. As the study was prematurely terminated, no analyses were conducted. Data for BFFS are listed by subject for those individuals who reported biochemical failure. Time (in months) to biochemical failure is relative to the date of brachytherapy.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

Up to 5 years

Results posted on

2019-09-18

Participant Flow

Subjects with recurrence of prostate cancer previously treated with radiotherapy were recruited in 11 sites in Spain from November 2011 until December 2014 when the study was prematurely discontinued.

35 subjects were screened and 3 did not meet inclusion criteria. Of those who met the inclusion criteria and none of the exclusion criteria, 32 were randomised to treatment and 31 received treatment after 1 subject (in the Brachytherapy + Triptorelin arm) withdrew consent.

Participant milestones

Participant milestones
Measure	Brachytherapy Subjects were randomised to receive brachytherapy alone, as either a low dose rate (\[125\]I) or high dose rate (\[192\]I).	Brachytherapy + Triptorelin 22.5 mg Subjects received brachytherapy as either a low dose rate (\[125\]I) or high dose rate (\[192\]I). Subjects also received a single intramuscular injection of 22.5 milligrams (mg) triptorelin at Visit 2 (Day 1).
Overall Study STARTED	16	15
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	16	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Brachytherapy Subjects were randomised to receive brachytherapy alone, as either a low dose rate (\[125\]I) or high dose rate (\[192\]I).	Brachytherapy + Triptorelin 22.5 mg Subjects received brachytherapy as either a low dose rate (\[125\]I) or high dose rate (\[192\]I). Subjects also received a single intramuscular injection of 22.5 milligrams (mg) triptorelin at Visit 2 (Day 1).
Overall Study Adverse Event	1	0
Overall Study Disease progression	2	2
Overall Study Study discontinued	13	13

Baseline Characteristics

Study to Assess the Efficacy of Brachytherapy With or Without Hormone Therapy, Using Triptorelin 22.5mg in Patients With Recurrence of Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brachytherapy n=16 Participants Subjects were randomised to receive brachytherapy alone, as either a low dose rate (\[125\]I) or high dose rate (\[192\]I).	Brachytherapy + Triptorelin 22.5 mg n=15 Participants Subjects received brachytherapy as either a low dose rate (\[125\]I) or high dose rate (\[192\]I). Subjects also received a single intramuscular injection of 22.5 mg triptorelin at Visit 2 (Day 1).	Total n=31 Participants Total of all reporting groups
Age, Continuous	67.50 years n=5 Participants	70.00 years n=7 Participants	68.00 years 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	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian/White	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants
Region of Enrollment Spain	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Population: A total of 3 subjects in each treatment group reported biochemical failure. The subject numbers assigned in the study are not presented. The subjects with biochemical failure are listed as Subject 1 to Subject 6, with these bearing no relation to the subject numbers used for other endpoints herein.

Outcome measures

Outcome measures
Measure	Brachytherapy n=3 Participants Subjects were randomised to receive brachytherapy alone, as either a low dose rate (\[125\]I) or high dose rate (\[192\]I).	Brachytherapy + Triptorelin 22.5 mg n=3 Participants Subjects received brachytherapy as either a low dose rate (\[125\]I) or high dose rate (\[192\]I). Subjects also received a single intramuscular injection of 22.5 mg triptorelin at Visit 2 (Day 1).
Biochemical Failure-free Survival (BFFS) Subject 3	5.7 Months	NA Months Subject not treated in this study arm.
Biochemical Failure-free Survival (BFFS) Subject 4	NA Months Subject not treated in this study arm.	24.7 Months
Biochemical Failure-free Survival (BFFS) Subject 1	5.2 Months	NA Months Subject not treated in this study arm.
Biochemical Failure-free Survival (BFFS) Subject 2	12.2 Months	NA Months Subject not treated in this study arm.
Biochemical Failure-free Survival (BFFS) Subject 5	NA Months Subject not treated in this study arm.	29.9 Months
Biochemical Failure-free Survival (BFFS) Subject 6	NA Months Subject not treated in this study arm.	5.6 Months

SECONDARY outcome

Timeframe: Up to 5 years

Population: A total of 3 subjects in the brachytherapy group and 4 subjects in the brachytherapy + triptorelin 22.5 mg group reported treatment failure. The subject numbers assigned in the study are not presented. The subjects with progression are listed as Subjects 1 to 7, with these bearing no relation to the subject numbers used for other endpoints herein.

Time to progression (in months) was measured from the informed consent date to the date of first event occurrence. Progression was defined as either: death from all causes or disease progression (defined as PSA increased by 2 ng/mL as compared to the pre-trial nadir PSA, confirmed during follow-up by a second value after 3 or more weeks, or the diagnosis of a new clinical recurrence of their prostate cancer (metastasis, new injury, etc.)). As the study was prematurely terminated, no analyses were conducted. Data for time to progression are listed by subject for those individuals who reported progression.

Outcome measures

Outcome measures
Measure	Brachytherapy n=3 Participants Subjects were randomised to receive brachytherapy alone, as either a low dose rate (\[125\]I) or high dose rate (\[192\]I).	Brachytherapy + Triptorelin 22.5 mg n=4 Participants Subjects received brachytherapy as either a low dose rate (\[125\]I) or high dose rate (\[192\]I). Subjects also received a single intramuscular injection of 22.5 mg triptorelin at Visit 2 (Day 1).
Time to Progression Subject 1	6.7 Months	NA Months Subject not treated in this study arm.
Time to Progression Subject 2	12.6 Months	NA Months Subject not treated in this study arm.
Time to Progression Subject 3	6.5 Months	NA Months Subject not treated in this study arm.
Time to Progression Subject 4	NA Months Subject not treated in this study arm.	27.2 Months
Time to Progression Subject 5	NA Months Subject not treated in this study arm.	30.8 Months
Time to Progression Subject 6	NA Months Subject not treated in this study arm.	16.8 Months
Time to Progression Subject 7	NA Months Subject not treated in this study arm.	12.8 Months

SECONDARY outcome

Timeframe: 5 years

Population: No data analyses were conducted as the study was terminated prior to completion of the 5-year follow-up.

A subject had a biochemical failure if there was an increase of PSA of 2 ng/mL or more in comparison with the pre-study nadir PSA confirmed in the course of follow-up by a second value after 3 or more weeks or with diagnosis of a new clinical recurrence of their prostate cancer over the 5 year follow-up.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 5 years

Population: No data analyses for Overall Survival were conducted as the study was terminated prior to completion of the 5 year follow-up.

Overall survival was defined as the time in months from diagnosis (biopsy date for local recurrence) to death due to any cause, the last visit or the loss to follow-up.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 3, 6 and 12 months

Population: The Safety population consisted of all randomised subjects who received at least one dose of study medication. Only subjects with data available at each timepoint are included.

Blood samples were drawn for serum testosterone at baseline (Visit 1) and then at 3, 6 and 12 months. Changes from baseline in total serum testosterone levels in relation to the normal parameter ranges are indicated. WNR = Within Normal Range, BNR= Below Normal Range and ANR = Above Normal Range.

Outcome measures

Outcome measures
Measure	Brachytherapy n=16 Participants Subjects were randomised to receive brachytherapy alone, as either a low dose rate (\[125\]I) or high dose rate (\[192\]I).	Brachytherapy + Triptorelin 22.5 mg n=15 Participants Subjects received brachytherapy as either a low dose rate (\[125\]I) or high dose rate (\[192\]I). Subjects also received a single intramuscular injection of 22.5 mg triptorelin at Visit 2 (Day 1).
Number of Participants With Change in Total Serum Testosterone Levels From Baseline at 3, 6 and 12 Months WNR at Baseline and Month 3	6 Participants	0 Participants
Number of Participants With Change in Total Serum Testosterone Levels From Baseline at 3, 6 and 12 Months WNR at Baseline, BNR at Month 3	1 Participants	7 Participants
Number of Participants With Change in Total Serum Testosterone Levels From Baseline at 3, 6 and 12 Months BNR at Baseline and Month 3	0 Participants	2 Participants
Number of Participants With Change in Total Serum Testosterone Levels From Baseline at 3, 6 and 12 Months WNR at Baseline and Month 6	5 Participants	2 Participants
Number of Participants With Change in Total Serum Testosterone Levels From Baseline at 3, 6 and 12 Months WNR at Baseline, BNR at Month 6	1 Participants	5 Participants
Number of Participants With Change in Total Serum Testosterone Levels From Baseline at 3, 6 and 12 Months BNR at Baseline and Month 6	0 Participants	2 Participants
Number of Participants With Change in Total Serum Testosterone Levels From Baseline at 3, 6 and 12 Months WNR at Baseline and Month 12	3 Participants	4 Participants
Number of Participants With Change in Total Serum Testosterone Levels From Baseline at 3, 6 and 12 Months WNR at Baseline, BNR at Month 12	3 Participants	2 Participants
Number of Participants With Change in Total Serum Testosterone Levels From Baseline at 3, 6 and 12 Months BNR at Baseline and Month 12	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and 3, 6 and 12 months

Population: The Safety population consisted of all randomised subjects who received at least one dose of study medication. Only subjects with data available at each timepoint are included.

Blood samples were drawn for serum PSA at baseline (Visit 1) and at 3, 6 and 12 months. Changes from baseline in total serum PSA levels in relation to the normal parameter ranges are indicated. WNR = Within Normal Range, BNR= Below Normal Range and ANR = Above Normal Range.

Outcome measures

Outcome measures
Measure	Brachytherapy n=16 Participants Subjects were randomised to receive brachytherapy alone, as either a low dose rate (\[125\]I) or high dose rate (\[192\]I).	Brachytherapy + Triptorelin 22.5 mg n=15 Participants Subjects received brachytherapy as either a low dose rate (\[125\]I) or high dose rate (\[192\]I). Subjects also received a single intramuscular injection of 22.5 mg triptorelin at Visit 2 (Day 1).
Number of Participants With Change in Total Serum PSA Levels From Baseline at 3, 6 and 12 Months WNR at Baseline and Month 3	3 Participants	2 Participants
Number of Participants With Change in Total Serum PSA Levels From Baseline at 3, 6 and 12 Months ANR at Baseline and Month 3	2 Participants	0 Participants
Number of Participants With Change in Total Serum PSA Levels From Baseline at 3, 6 and 12 Months ANR at Baseline, WNR at Month 3	7 Participants	5 Participants
Number of Participants With Change in Total Serum PSA Levels From Baseline at 3, 6 and 12 Months WNR at Baseline and Month 6	2 Participants	5 Participants
Number of Participants With Change in Total Serum PSA Levels From Baseline at 3, 6 and 12 Months WNR at Baseline, BNR at Month 6	0 Participants	1 Participants
Number of Participants With Change in Total Serum PSA Levels From Baseline at 3, 6 and 12 Months ANR at Baseline and Month 6	3 Participants	0 Participants
Number of Participants With Change in Total Serum PSA Levels From Baseline at 3, 6 and 12 Months ANR at Baseline and WNR at Month 6	6 Participants	3 Participants
Number of Participants With Change in Total Serum PSA Levels From Baseline at 3, 6 and 12 Months WNR at Baseline and Month 12	1 Participants	4 Participants
Number of Participants With Change in Total Serum PSA Levels From Baseline at 3, 6 and 12 Months WNR at Baseline, BNR at Month 12	0 Participants	1 Participants
Number of Participants With Change in Total Serum PSA Levels From Baseline at 3, 6 and 12 Months ANR at Baseline and Month 12	1 Participants	0 Participants
Number of Participants With Change in Total Serum PSA Levels From Baseline at 3, 6 and 12 Months ANR at Baseline, WNR at Month 12	4 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline and 5 years.

Population: No data analyses for change from baseline score for QoL modifications were conducted as the study was terminated prior to completion of the 5 year follow-up.

EPIC assessed the disease-specific aspects of prostate cancer and its therapies and comprised four summary domains (Urinary, Bowel, Sexual and Hormonal). Factor analysis supported dividing the Urinary Domain Summary Score into two different Incontinence and Irritative/Obstructive subscales. In addition, each Domain Summary Score had measurable Function Subscale and Bother Subscale components. Response options for each EPIC item formed a Likert scale, and multi-item scale scores were transformed linearly to a 0-100 scale, with higher scores representing better Health-Related QoL.

Outcome measures

Outcome data not reported

Adverse Events

Brachytherapy

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Brachytherapy + Triptorelin 22.5 mg

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Brachytherapy n=16 participants at risk Subjects were randomised to receive brachytherapy alone, as either a low dose rate (\[125\]I) or high dose rate (\[192\]I).	Brachytherapy + Triptorelin 22.5 mg n=15 participants at risk Subjects received brachytherapy as either a low dose rate (\[125\]I) or high dose rate (\[192\]I). Subjects also received a single intramuscular injection of 22.5 mg triptorelin at Visit 2 (Day 1).
Cardiac disorders Myocardial infarction	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Infections and infestations Liver abscess	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Infections and infestations Necrotising fasciitis	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Infections and infestations Orchitis	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Infections and infestations Pneumonia	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Infections and infestations Scrotal abscess	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Renal and urinary disorders Haematuria	6.2% 1/16 • Number of events 3 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.

Other adverse events

Additional Information

Medical Director

Ipsen

Phone: use email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor required reasonable opportunity to review any summary, presentation, or paper before the material was submitted for publication or communicated. This also applied to any amendments that were requested by evaluators or journal directors. The Sponsor committed to comment on the draft documents within a time period agreed in the contractual provisions between the Sponsor and authors or their institutions. Delays were also possible if publication would adversely affect patentability.
Publication restrictions are in place

Restriction type: OTHER

Measure	Brachytherapy n=16 participants at risk Subjects were randomised to receive brachytherapy alone, as either a low dose rate (\[125\]I) or high dose rate (\[192\]I).	Brachytherapy + Triptorelin 22.5 mg n=15 participants at risk Subjects received brachytherapy as either a low dose rate (\[125\]I) or high dose rate (\[192\]I). Subjects also received a single intramuscular injection of 22.5 mg triptorelin at Visit 2 (Day 1).
Gastrointestinal disorders Anal pruritus	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Anorectal disorder	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Constipation	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 2 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Dyspepsia	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Nausea	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Proctitis	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Vomiting	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
General disorders Catheter site haemorrhage	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
General disorders Implant site pain	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
General disorders Puncture site pain	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Infections and infestations Erythrasma	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Infections and infestations Orchitis	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Infections and infestations Pilonidal cyst	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Infections and infestations Urinary tract infection	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Radiation skin injury	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	12.5% 2/16 • Number of events 2 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Renal and urinary disorders Dysuria	18.8% 3/16 • Number of events 4 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	26.7% 4/15 • Number of events 5 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Renal and urinary disorders Haematuria	12.5% 2/16 • Number of events 2 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	20.0% 3/15 • Number of events 3 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Renal and urinary disorders Hypertonic bladder	12.5% 2/16 • Number of events 3 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Renal and urinary disorders Incontinence	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Renal and urinary disorders Micturition urgency	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Renal and urinary disorders Nephropathy toxic	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Renal and urinary disorders Nocturia	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Renal and urinary disorders Pollakiuria	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Renal and urinary disorders Urinary incontinence	12.5% 2/16 • Number of events 2 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 2 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Renal and urinary disorders Urinary retention	18.8% 3/16 • Number of events 3 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Reproductive system and breast disorders Nipple pain	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Reproductive system and breast disorders Perineal pain	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Reproductive system and breast disorders Pruritus genital	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Suffocation feeling	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Vascular disorders Blood pressure inadequately controlled	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Vascular disorders Flushing	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Vascular disorders Hypertensive crisis	0.00% 0/16 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.
Vascular disorders Hypotension	6.2% 1/16 • Number of events 1 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.	0.00% 0/15 • Treatment emergent adverse events were collected from treatment initiation (Day 1) to end of the study (up to 5 years). The Safety population consisted of all randomised subjects who received at least 1 dose of study medication.