Trial Outcomes & Findings for Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Neurogenic Overactive Bladder (NCT NCT00311376)

Last Updated: 2015-12-04

Results Overview

Change from baseline in the weekly frequency of incontinence episodes at Week 6 after the first treatment. Incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary. A negative number change from baseline indicates a reduction in incontinence episodes (improvement).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

416 participants

Primary outcome timeframe

Baseline, Week 6

Results posted on

2015-12-04

Participant Flow

Participant milestones

Participant milestones
Measure	Botulinum Toxin Type A (300U) botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) botulinum toxin Type A (200U)	Placebo Normal saline (placebo)
Treatment Cycle 1 STARTED	132	135	149
Treatment Cycle 1 COMPLETED	105	118	132
Treatment Cycle 1 NOT COMPLETED	27	17	17
Treatment Cycle 2 STARTED	115	125	0
Treatment Cycle 2 COMPLETED	106	112	0
Treatment Cycle 2 NOT COMPLETED	9	13	0

Reasons for withdrawal

Withdrawal data not reported

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 (300U) n=132 Participants botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) n=135 Participants botulinum toxin Type A (200U)	Placebo n=149 Participants Normal saline (placebo)	Total n=416 Participants Total of all reporting groups
Age, Customized <40 years	40 participants n=93 Participants	48 participants n=4 Participants	45 participants n=27 Participants	133 participants n=483 Participants
Age, Customized Between 40 and 64 years	83 participants n=93 Participants	73 participants n=4 Participants	95 participants n=27 Participants	251 participants n=483 Participants
Age, Customized Between 65 and 74 years	9 participants n=93 Participants	14 participants n=4 Participants	9 participants n=27 Participants	32 participants n=483 Participants
Age, Customized >=75 years	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants
Sex: Female, Male Female	89 Participants n=93 Participants	80 Participants n=4 Participants	76 Participants n=27 Participants	245 Participants n=483 Participants
Sex: Female, Male Male	43 Participants n=93 Participants	55 Participants n=4 Participants	73 Participants n=27 Participants	171 Participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline, Week 6

Population: Intent-to-Treat defined as all patients who started the study (randomized)

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A (300U) n=132 Participants botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) n=135 Participants botulinum toxin Type A (200U)	Placebo n=149 Participants Normal saline (placebo)
Change From Baseline in Number of Weekly Episodes of Urinary Incontinence Baseline	31.1 Number of Weekly Episodes Standard Deviation 17.02	32.3 Number of Weekly Episodes Standard Deviation 22.76	28.3 Number of Weekly Episodes Standard Deviation 15.82
Change From Baseline in Number of Weekly Episodes of Urinary Incontinence Week 6	-22.7 Number of Weekly Episodes Standard Deviation 17.10	-21.0 Number of Weekly Episodes Standard Deviation 23.77	-8.8 Number of Weekly Episodes Standard Deviation 16.18

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Intent-to-Treat defined as all patients who started the study (randomized)

Change from baseline in MCC at week 6. MCC represents the maximum volume of urine the bladder holds. A positive number change from baseline represents an improvement (increase) in maximum volume of urine the bladder holds.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A (300U) n=132 Participants botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) n=135 Participants botulinum toxin Type A (200U)	Placebo n=149 Participants Normal saline (placebo)
Change From Baseline in Maximum Cystometric Capacity (MCC) Baseline	255.8 Millimeters (mL) of urine Standard Deviation 144.99	252.3 Millimeters (mL) of urine Standard Deviation 154.37	256.0 Millimeters (mL) of urine Standard Deviation 143.83
Change From Baseline in Maximum Cystometric Capacity (MCC) Week 6	167.7 Millimeters (mL) of urine Standard Deviation 169.56	151.2 Millimeters (mL) of urine Standard Deviation 170.59	15.5 Millimeters (mL) of urine Standard Deviation 127.31

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Intent-to-Treat defined as all patients who started the study (randomized)

Change from baseline in MDP during first involuntary detrusor contraction at week 6. MDP represents the maximum pressure (peak amplitude) in the bladder during the first involuntary contraction of the bladder muscle. The greater the negative number change from baseline, the better the improvement.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A (300U) n=132 Participants botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) n=135 Participants botulinum toxin Type A (200U)	Placebo n=149 Participants Normal saline (placebo)
Change From Baseline in Maximum Detrusor Pressure (MDP) Baseline	47.1 Centimeters of water (cm H20) Standard Deviation 36.30	51.3 Centimeters of water (cm H20) Standard Deviation 34.66	50.9 Centimeters of water (cm H20) Standard Deviation 38.08
Change From Baseline in Maximum Detrusor Pressure (MDP) Week 6	-33.3 Centimeters of water (cm H20) Standard Deviation 37.75	-35.1 Centimeters of water (cm H20) Standard Deviation 35.67	-2.4 Centimeters of water (cm H20) Standard Deviation 43.41

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Intent-to-Treat defined as all patients who started the study (randomized)

Change from baseline in I-QOL questionnaire total score at Week 6, as completed by the patient. The I-QOL is a validated, disease-specific quality of life (QOL) questionnaire containing 22 questions designed to measure impact of urinary incontinence on patients' lives. Each question is answered on a 5-point scale (1 = worst QOL and 5 = best QOL). The scores are totaled over the 22 questions and normalized to a score of 0-100 (0 = worst QOL and 100= best QOL). A positive change from baseline represents an improvement

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A (300U) n=132 Participants botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) n=135 Participants botulinum toxin Type A (200U)	Placebo n=149 Participants Normal saline (placebo)
Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire Baseline	32.18 Number on a Scale (Score) Standard Deviation 18.609	33.95 Number on a Scale (Score) Standard Deviation 18.021	35.06 Number on a Scale (Score) Standard Deviation 18.066
Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire Week 6	32.92 Number on a Scale (Score) Standard Deviation 23.849	26.90 Number on a Scale (Score) Standard Deviation 26.813	10.81 Number on a Scale (Score) Standard Deviation 18.413

Adverse Events

Botulinum Toxin Type A (300U)

Serious events: 30 serious events

Other events: 82 other events

Deaths: 0 deaths

Botulinum Toxin Type A (200U)

Serious events: 24 serious events

Other events: 92 other events

Deaths: 0 deaths

Placebo

Serious events: 22 serious events

Other events: 70 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Botulinum Toxin Type A (300U) n=127 participants at risk botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) n=135 participants at risk botulinum toxin Type A (200U)	Placebo n=145 participants at risk Normal saline (placebo)
Gastrointestinal disorders Nausea	6.3% 8/127 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	4.4% 6/135 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	2.1% 3/145 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
Gastrointestinal disorders Diarrhoea	5.5% 7/127 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	5.9% 8/135 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	2.8% 4/145 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
General disorders Pyrexia	3.1% 4/127 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	7.4% 10/135 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	3.4% 5/145 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
General disorders Fatigue	3.1% 4/127 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	5.9% 8/135 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	4.1% 6/145 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
Infections and infestations Urinary tract infection	50.4% 64/127 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	48.9% 66/135 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	33.8% 49/145 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
Infections and infestations Vulvovaginal mycotic infection	3.4% 3/89 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	7.5% 6/80 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	2.6% 2/76 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
Musculoskeletal and connective tissue disorders Muscular weakness	7.1% 9/127 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	3.0% 4/135 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	2.8% 4/145 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
Nervous system disorders Multiple sclerosis relapse	9.4% 12/127 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	0.74% 1/135 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	2.1% 3/145 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
Nervous system disorders Headache	5.5% 7/127 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	3.0% 4/135 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	2.8% 4/145 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
Renal and urinary disorders Urinary retention	17.3% 22/127 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	20.0% 27/135 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	3.4% 5/145 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
Renal and urinary disorders Bladder pain	5.5% 7/127 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	1.5% 2/135 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	1.4% 2/145 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
Renal and urinary disorders Haematuria	4.7% 6/127 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	5.2% 7/135 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	2.8% 4/145 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
Vascular disorders Hypertension	5.5% 7/127 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	2.2% 3/135 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.	0.00% 0/145 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.

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