Trial Outcomes & Findings for A Study of Intravesical Apaziquone as a Surgical Adjuvant in Participant Undergoing Transurethral Resection Bladder Tumor (TURBT) (NCT NCT02563561)

Last Updated: 2021-10-27

Results Overview

Time from randomization to the date of histologically confirmed recurrence of bladder cancer. A recurrence was defined as any pathologically confirmed disease of ≥Ta tumor histology or carcinoma in situ (CIS) post-treatment.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

62 participants

Primary outcome timeframe

From randomization to the date of first histologically confirmed recurrence of bladder cancer (up to 1.5 years)

Results posted on

2021-10-27

Participant Flow

Participants who underwent Transurethral Resection for Non-Muscle Invasive Bladder Cancer (NIMBC) were enrolled at 17 investigative sites in the United States and Canada from 09 Oct 2015 to 10 March 2017.

A total of 62 participants were randomized into the study, out of which 6 participants completed the study.

Participant milestones

Participant milestones
Measure	1 Dose Apaziquone Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post transurethral resection of bladder tumor (TURBT) on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).	2 Dose Apaziquone Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of 4 mg of apaziquone by intravesical administration via an indwelling catheter on Day 15 (±5 days).	Placebo Participants were randomized to receive first dose of matching placebo by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of matching placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).
Overall Study STARTED	19	23	20
Overall Study Safety Population	19	21	17
Overall Study COMPLETED	1	2	3
Overall Study NOT COMPLETED	18	21	17

Reasons for withdrawal

Reasons for withdrawal
Measure	1 Dose Apaziquone Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post transurethral resection of bladder tumor (TURBT) on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).	2 Dose Apaziquone Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of 4 mg of apaziquone by intravesical administration via an indwelling catheter on Day 15 (±5 days).	Placebo Participants were randomized to receive first dose of matching placebo by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of matching placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).
Overall Study Histology Other than Ta, G1-G2	3	6	6
Overall Study Withdrew of Consent	1	1	2
Overall Study Lost to Follow-up	1	1	0
Overall Study Participant Had Recurrence and Received Therapy	4	2	1
Overall Study Investigator Decision	3	4	2
Overall Study Sponsor Decision	5	2	4
Overall Study Other	1	5	2

Baseline Characteristics

A Study of Intravesical Apaziquone as a Surgical Adjuvant in Participant Undergoing Transurethral Resection Bladder Tumor (TURBT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1 Dose Apaziquone n=19 Participants Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post transurethral resection of bladder tumor (TURBT) on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).	2 Dose Apaziquone n=21 Participants Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of 4 mg of apaziquone by intravesical administration via an indwelling catheter on Day 15 (±5 days).	Placebo n=17 Participants Participants were randomized to receive first dose of matching placebo by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of matching placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).	Total n=57 Participants Total of all reporting groups
Age, Continuous	67.5 years STANDARD_DEVIATION 9.2 • n=5 Participants	66.6 years STANDARD_DEVIATION 12.4 • n=7 Participants	66.1 years STANDARD_DEVIATION 12.4 • n=5 Participants	66.7 years STANDARD_DEVIATION 11.2 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	14 Participants n=7 Participants	11 Participants n=5 Participants	39 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	21 Participants n=7 Participants	14 Participants n=5 Participants	53 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	20 Participants n=7 Participants	17 Participants n=5 Participants	55 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: From randomization to the date of first histologically confirmed recurrence of bladder cancer (up to 1.5 years)

Population: Data for this outcome measure was not collected due to early termination of study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Population: Data for this outcome measure was not collected due to early termination of study.

The percentage of participants with histologically confirmed recurrence of the bladder tumor at any time after randomization and on or before Year 2. A recurrence was defined as any pathologically confirmed disease of ≥Ta tumor histology or CIS post-treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Population: Data for this outcome measure was not collected due to early termination of study.

The percentage of participants with histologically confirmed recurrence of the bladder tumor at any time after randomization and on or before Year 1. A recurrence was defined as any pathologically confirmed disease of ≥Ta tumor histology or CIS post-treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From randomization to the date of first disease progression (up to 1.5 years)

Population: Data for this outcome measure was not collected due to early termination of study.

Time to disease progression was defined as the time from randomization to the first disease progression. The development of T2 or greater disease was only included in the assessment of time to disease progression.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 1.5 Years

Population: Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.

An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. TEAEs were adverse events that occurred from the first dose of study treatment until 40 days after the last dose of study drug administration or 40 days after the date of participant early discontinuation. Treatment-related AEs included TEAEs with relationship to study treatment reported as possible, probable, definite, or missing. An SAE was an AE resulting in any of the outcomes: death; initial/prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly.

Outcome measures

Outcome measures
Measure	1 Dose Apaziquone n=19 Participants Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).	2 Dose Apaziquone n=21 Participants Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of 4 mg of apaziquone by intravesical administration via an indwelling catheter on Day 15 (±5 days).	Placebo n=17 Participants Participants were randomized to receive first dose of matching placebo by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of matching placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and Death TEAEs	10 Participants	13 Participants	7 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and Death Treatment-Related AEs	4 Participants	4 Participants	5 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and Death SAEs	0 Participants	2 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and Death TEAEs Leading to Discontinuation	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and Death Death	0 Participants	0 Participants	0 Participants

Adverse Events

1 Dose Apaziquone

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

2 Dose Apaziquone

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1 Dose Apaziquone n=19 participants at risk Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).	2 Dose Apaziquone n=21 participants at risk Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of 4 mg of apaziquone by intravesical administration via an indwelling catheter on Day 15 (±5 days).	Placebo n=17 participants at risk Participants were randomized to receive first dose of matching placebo by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of matching placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).
Renal and urinary disorders Bladder Perforation	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	4.8% 1/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Gastrointestinal disorders Colitis Ischaemic	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	4.8% 1/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Gastrointestinal disorders Large Intestine Perforation	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Gastrointestinal disorders Large Intestinal Stenosis	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.

Other adverse events

Additional Information

Shanta Chawla

Spectrum Pharmaceuticals, Inc. Research and Development Office 157 Technology Drive Irvine, CA 92618

Phone: (949) 788-6700

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	1 Dose Apaziquone n=19 participants at risk Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).	2 Dose Apaziquone n=21 participants at risk Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of 4 mg of apaziquone by intravesical administration via an indwelling catheter on Day 15 (±5 days).	Placebo n=17 participants at risk Participants were randomized to receive first dose of matching placebo by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of matching placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).
Blood and lymphatic system disorders Leukocytosis	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Endocrine disorders Adrenal Mass	5.3% 1/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	4.8% 1/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Gastrointestinal disorders Abdominal Discomfort	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Gastrointestinal disorders Abdominal Distension	5.3% 1/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Gastrointestinal disorders Nausea	5.3% 1/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	4.8% 1/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Gastrointestinal disorders Vomiting	5.3% 1/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
General disorders Fatigue	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	4.8% 1/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
General disorders Influenza Like Illness	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Injury, poisoning and procedural complications Post Procedural Discomfort	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Injury, poisoning and procedural complications Procedural Pain	5.3% 1/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive Ductal Breast Carcinoma	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Nervous system disorders Cervical Radiculopathy	5.3% 1/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Nervous system disorders Headache	10.5% 2/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Renal and urinary disorders Bladder Pain	10.5% 2/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	9.5% 2/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Renal and urinary disorders Bladder Spasm	10.5% 2/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	19.0% 4/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Renal and urinary disorders Dysuria	21.1% 4/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	33.3% 7/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	11.8% 2/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Renal and urinary disorders Haematuria	5.3% 1/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	14.3% 3/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Renal and urinary disorders Micturition Urgency	10.5% 2/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Renal and urinary disorders Nocturia	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	9.5% 2/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Renal and urinary disorders Pollakiuria	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	4.8% 1/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Renal and urinary disorders Urinary Hesitation	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Renal and urinary disorders Urinary Retention	5.3% 1/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	4.8% 1/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Renal and urinary disorders Urine Abnormality	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	4.8% 1/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	5.9% 1/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
Respiratory, thoracic and mediastinal disorders Sleep Apnoea Syndrome	5.3% 1/19 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/21 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.	0.00% 0/17 • Up to 1.5 years Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.