Trial Outcomes & Findings for Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Neurogenic Overactive Bladder (NCT NCT00439140)

Last Updated: 2014-01-24

Results Overview

Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FVC, the maximum amount of air exhaled from the lungs after taking the deepest breath possible, at Baseline and Week 6. A positive change from Baseline indicated improvement.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

41 participants

Primary outcome timeframe

Baseline, Week 6

Results posted on

2014-01-24

Participant Flow

Botulinum toxin Type A 300U was discontinued from the study after regulatory approval of botulinum toxin Type A 200U. Patients remaining in the study who were allocated to receive botulinum toxin Type A 300U at treatment 2 (and had not yet received it) received botulinum toxin Type A 200U instead.

Participant milestones

Participant milestones
Measure	Botulinum Toxin Type A 200U Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Botulinum Toxin Type A 300U Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Placebo Placebo (Normal Saline) injection into the detrusor on Day 1. (If applicable after 12 weeks, participants received either botulinum toxin Type A 200U or 300U in Treatment Cycle 2.)
Treatment Cycle 1 STARTED	15	14	12
Treatment Cycle 1 COMPLETED	14	10	11
Treatment Cycle 1 NOT COMPLETED	1	4	1
Treatment Cycle 2 STARTED	13	7	0
Treatment Cycle 2 COMPLETED	11	6	0
Treatment Cycle 2 NOT COMPLETED	2	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Botulinum Toxin Type A 200U Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Botulinum Toxin Type A 300U Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Placebo Placebo (Normal Saline) injection into the detrusor on Day 1. (If applicable after 12 weeks, participants received either botulinum toxin Type A 200U or 300U in Treatment Cycle 2.)
Treatment Cycle 1 Lost to Follow-up	1	1	1
Treatment Cycle 1 Personal reasons	0	2	0
Treatment Cycle 1 Withdrawal by Subject	0	1	0
Treatment Cycle 2 Withdrawal by Subject	1	0	0
Treatment Cycle 2 Lost to Follow-up	1	1	0

Baseline Characteristics

Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Neurogenic Overactive Bladder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Botulinum Toxin Type A 200U n=15 Participants Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Botulinum Toxin Type A 300U n=14 Participants Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Placebo/Botulinum Toxin Type A n=12 Participants Placebo (Normal Saline) injection into the detrusor on Day 1 followed by a botulinum toxin Type A 200U or 300U injection after a minimum of 12 weeks (if applicable).	Total n=41 Participants Total of all reporting groups
Age, Customized < 40 Years	9 participants n=5 Participants	8 participants n=7 Participants	6 participants n=5 Participants	23 participants n=4 Participants
Age, Customized 40-64 Years	4 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	16 participants n=4 Participants
Age, Customized ≥ 65 Years	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	16 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	25 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 6

Population: Safety Population included all randomized participants who received treatment.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A 200U n=15 Participants Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Botulinum Toxin Type A 300U n=14 Participants Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Placebo n=12 Participants Placebo (Normal Saline) injection into the detrusor on Day 1.
Change From Baseline in Forced Vital Capacity (FVC) Baseline	2.659 Liters Standard Deviation 0.5308	2.955 Liters Standard Deviation 0.7733	3.095 Liters Standard Deviation 0.6868
Change From Baseline in Forced Vital Capacity (FVC) Change from Baseline at Week 6	-0.124 Liters Standard Deviation 0.2758	-0.096 Liters Standard Deviation 0.2248	-0.025 Liters Standard Deviation 0.2391

PRIMARY outcome

Timeframe: Baseline, Week 6

Population: Safety population included all randomized participants who received treatment.

Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FEV1, the maximum amount of air exhaled in one second, at Baseline and Week 6. The highest value at each time-point was recorded. A positive change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A 200U n=15 Participants Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Botulinum Toxin Type A 300U n=14 Participants Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Placebo n=12 Participants Placebo (Normal Saline) injection into the detrusor on Day 1.
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Baseline	2.290 Liters Standard Deviation 0.5815	2.534 Liters Standard Deviation 0.7227	2.535 Liters Standard Deviation 0.7626
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Change from Baseline at Week 6	-0.067 Liters Standard Deviation 0.2525	-0.094 Liters Standard Deviation 0.2196	-0.052 Liters Standard Deviation 0.1926

PRIMARY outcome

Timeframe: Baseline, Week 6

Population: Safety population included all randomized participants who received treatment.

The FEV1/FVC ratio was calculated by dividing the FEV1 value by the FVC value representing the portion (or ratio) of FVC exhaled in one second. A positive change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A 200U n=15 Participants Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Botulinum Toxin Type A 300U n=14 Participants Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Placebo n=12 Participants Placebo (Normal Saline) injection into the detrusor on Day 1.
Change From Baseline in FEV1/FVC Ratio Baseline	0.857 Ratio Standard Deviation 0.1093	0.857 Ratio Standard Deviation 0.1214	0.818 Ratio Standard Deviation 0.1574
Change From Baseline in FEV1/FVC Ratio Change from Baseline at Week 6	0.017 Ratio Standard Deviation 0.0668	-0.007 Ratio Standard Deviation 0.0578	-0.018 Ratio Standard Deviation 0.0676

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants from the Intent-to-treat population (all randomized participants) using observed data for analysis.

The number of urinary incontinence episodes or leakage occurring over the previous 3 days was recorded in the patient bladder diary at Baseline and prior to Week 6. A negative change from Baseline indicated improvement (less incontinence/leakage).

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A 200U n=15 Participants Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Botulinum Toxin Type A 300U n=13 Participants Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Placebo n=11 Participants Placebo (Normal Saline) injection into the detrusor on Day 1.
Change From Baseline in the Number of Urinary Incontinence Episodes Baseline	12.5 Episodes Standard Deviation 9.78	13.5 Episodes Standard Deviation 6.48	9.3 Episodes Standard Deviation 6.59
Change From Baseline in the Number of Urinary Incontinence Episodes Change from Baseline at Week 6 (n=13,11,11)	-10.2 Episodes Standard Deviation 7.70	-9.5 Episodes Standard Deviation 6.96	-3.4 Episodes Standard Deviation 4.57

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Intent-to-treat population included all randomized participants.

MDP was measured at the first involuntary detrusor contraction using urodynamic testing. A catheter was inserted into the bladder at Baseline and Week 6 and the pressure \[measured in centimeters water (cm H20)\] was determined as the bladder filled. A negative change from Baseline indicated improvement (less Detrusor pressure).

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A 200U n=15 Participants Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Botulinum Toxin Type A 300U n=14 Participants Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Placebo n=12 Participants Placebo (Normal Saline) injection into the detrusor on Day 1.
Change From Baseline in the Maximum (Amplitude) Detrusor Pressure (MDP) Baseline	39.1 cm H2O Standard Deviation 30.45	42.6 cm H2O Standard Deviation 22.65	41.9 cm H2O Standard Deviation 18.91
Change From Baseline in the Maximum (Amplitude) Detrusor Pressure (MDP) Change from Baseline at Week 6 (n=4,9,9)	-23.3 cm H2O Standard Deviation 28.96	0.3 cm H2O Standard Deviation 32.67	8.7 cm H2O Standard Deviation 23.91

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Intent-to-treat population included all randomized participants.

MCC (the maximum amount of urine the bladder could hold) was measured using urodynamic testing. The amount of urine collected was subtracted from the total volume infused measured as milliliters (mL) of urine. A positive change from Baseline indicated improvement (fuller bladder/ less incontinence).

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A 200U n=15 Participants Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Botulinum Toxin Type A 300U n=14 Participants Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Placebo n=12 Participants Placebo (Normal Saline) injection into the detrusor on Day 1.
Change From Baseline in Maximum Cystometric Capacity (MCC) Baseline	161.4 mL Standard Deviation 80.29	216.7 mL Standard Deviation 168.41	266.2 mL Standard Deviation 191.41
Change From Baseline in Maximum Cystometric Capacity (MCC) Change from Baseline at Week 6 (n=12,13,11)	213.2 mL Standard Deviation 135.58	60.2 mL Standard Deviation 222.35	-64.5 mL Standard Deviation 136.98

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Weeks 2, 6 and 12

Population: Safety population included all randomized participants who received treatment.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A 200U n=15 Participants Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Botulinum Toxin Type A 300U n=14 Participants Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Placebo n=12 Participants Placebo (Normal Saline) injection into the detrusor on Day 1.
Number of Participants With at Least a 15% Decrease From Baseline in FVC Week 6 (n=15,14,12)	2 Participants	1 Participants	0 Participants
Number of Participants With at Least a 15% Decrease From Baseline in FVC Week 2 (n=15,14,12)	0 Participants	1 Participants	1 Participants
Number of Participants With at Least a 15% Decrease From Baseline in FVC Week 12 (n=14,12,9)	0 Participants	1 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Weeks 2, 6 and 12

Population: Safety population included all randomized participants who received treatment.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A 200U n=15 Participants Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Botulinum Toxin Type A 300U n=14 Participants Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Placebo n=12 Participants Placebo (Normal Saline) injection into the detrusor on Day 1.
Number of Participants With at Least a 20% Decrease From Baseline in FVC Week 2 (n=15,14,12)	0 Participants	1 Participants	0 Participants
Number of Participants With at Least a 20% Decrease From Baseline in FVC Week 6 (n=15,14,12)	1 Participants	0 Participants	0 Participants
Number of Participants With at Least a 20% Decrease From Baseline in FVC Week 12 (n=14,12,9)	0 Participants	1 Participants	0 Participants

Adverse Events

Botulinum Toxin Type A 200U

Serious events: 4 serious events

Other events: 12 other events

Deaths: 0 deaths

Botulinum Toxin Type A 300U

Serious events: 6 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo/Botulinum Toxin Type A

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head,

Allergan, Inc

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	Botulinum Toxin Type A 200U n=15 participants at risk Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Botulinum Toxin Type A 300U n=14 participants at risk Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Placebo/Botulinum Toxin Type A n=12 participants at risk Placebo (Normal Saline) injection into the detrusor on Day 1 followed by a botulinum toxin Type A 200U or 300U injection after a minimum of 12 weeks (if applicable).
Infections and infestations Urinary tract infection	13.3% 2/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	14.3% 2/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Infections and infestations Lower respiratory tract infection	0.00% 0/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	7.1% 1/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Infections and infestations Upper respiratory tract infection	0.00% 0/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	7.1% 1/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Infections and infestations Cellulitis	6.7% 1/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Infections and infestations Leptospirosis	6.7% 1/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Infections and infestations Typhoid fever	6.7% 1/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Infections and infestations Septic shock	0.00% 0/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	8.3% 1/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Infections and infestations Urinary tract infection pseudomonal	0.00% 0/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	8.3% 1/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Infections and infestations Urosepsis	0.00% 0/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	8.3% 1/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Investigations Renal function test abnormal	0.00% 0/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	7.1% 1/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Spinal cord neoplasm	0.00% 0/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	7.1% 1/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Renal and urinary disorders Urinary incontinence	0.00% 0/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	7.1% 1/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Renal and urinary disorders Urinary retention	0.00% 0/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	7.1% 1/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Renal and urinary disorders Hydronephrosis	6.7% 1/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Renal and urinary disorders Calculus ureteric	0.00% 0/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	8.3% 1/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/15 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	7.1% 1/14 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.	0.00% 0/12 Serious Adverse Events (SAEs) and Adverse Events (AEs) were reported based on the treatment the participant received. SAEs and AEs reported for participants in the Placebo/Botulinum Toxin Type A arm may have occurred while the participant received placebo in Cycle 1 or botulinum toxin Type A in Cycle 2.