Trial Outcomes & Findings for Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Neurogenic Overactive Bladder (NCT NCT00461292)

Last Updated: 2015-10-02

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

275 participants

Primary outcome timeframe

Baseline, Week 6

Results posted on

2015-10-02

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	91	92	92
Treatment Cycle 1 COMPLETED	76	80	81
Treatment Cycle 1 NOT COMPLETED	15	12	11
Treatment Cycle 2 STARTED	63	74	0
Treatment Cycle 2 COMPLETED	58	72	0
Treatment Cycle 2 NOT COMPLETED	5	2	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=91 Participants botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) n=92 Participants botulinum toxin Type A (200U)	Placebo n=92 Participants Normal saline (placebo)	Total n=275 Participants Total of all reporting groups
Age, Customized < 40 years	30 participants n=5 Participants	31 participants n=7 Participants	25 participants n=5 Participants	86 participants n=4 Participants
Age, Customized Between 40 and 64 years	56 participants n=5 Participants	55 participants n=7 Participants	61 participants n=5 Participants	172 participants n=4 Participants
Age, Customized Between 65 and 74 years	4 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	14 participants n=4 Participants
Age, Customized >= 75 years	1 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	54 Participants n=7 Participants	49 Participants n=5 Participants	155 Participants n=4 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	38 Participants n=7 Participants	43 Participants n=5 Participants	120 Participants n=4 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=91 Participants botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) n=92 Participants botulinum toxin Type A (200U)	Placebo n=92 Participants Normal saline (placebo)
Change From Baseline in Number of Weekly Episodes of Urinary Incontinence Baseline	31.2 Number of Weekly Episodes Standard Deviation 18.14	32.5 Number of Weekly Episodes Standard Deviation 18.44	36.7 Number of Weekly Episodes Standard Deviation 30.67
Change From Baseline in Number of Weekly Episodes of Urinary Incontinence Week 6	-19.4 Number of Weekly Episodes Standard Deviation 25.67	-21.8 Number of Weekly Episodes Standard Deviation 18.06	-13.2 Number of Weekly Episodes Standard Deviation 20.02

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=91 Participants botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) n=92 Participants botulinum toxin Type A (200U)	Placebo n=92 Participants Normal saline (placebo)
Change From Baseline in Maximum Cystometric Capacity (MCC) Baseline	246.8 Milliliters (mL) of urine Standard Deviation 149.06	247.3 Milliliters (mL) of urine Standard Deviation 147.61	249.4 Milliliters (mL) of urine Standard Deviation 139.29
Change From Baseline in Maximum Cystometric Capacity (MCC) Week 6	157.2 Milliliters (mL) of urine Standard Deviation 185.18	157.0 Milliliters (mL) of urine Standard Deviation 164.75	6.5 Milliliters (mL) of urine Standard Deviation 144.77

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 the 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=91 Participants botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) n=92 Participants botulinum toxin Type A (200U)	Placebo n=92 Participants Normal saline (placebo)
Change From Baseline in Maximum Detrusor Pressure (MDP) Baseline	42.1 Centimeters of water (cm H2O) Standard Deviation 33.21	51.7 Centimeters of water (cm H2O) Standard Deviation 40.95	41.5 Centimeters of water (cm H2O) Standard Deviation 31.17
Change From Baseline in Maximum Detrusor Pressure (MDP) Week 6	-26.9 Centimeters of water (cm H2O) Standard Deviation 33.17	-28.5 Centimeters of water (cm H2O) Standard Deviation 47.82	6.4 Centimeters of water (cm H2O) Standard Deviation 41.10

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=91 Participants botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) n=92 Participants botulinum toxin Type A (200U)	Placebo n=92 Participants Normal saline (placebo)
Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire Baseline	36.32 Number on a Scale (Score) Standard Deviation 18.685	37.46 Number on a Scale (Score) Standard Deviation 20.109	35.72 Number on a Scale (Score) Standard Deviation 18.656
Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire Week 6	24.26 Number on a Scale (Score) Standard Deviation 28.981	24.43 Number on a Scale (Score) Standard Deviation 25.372	11.71 Number on a Scale (Score) Standard Deviation 20.163

Adverse Events

Botulinum Toxin Type A (300U)

Serious events: 18 serious events

Other events: 70 other events

Deaths: 0 deaths

Botulinum Toxin Type A (200U)

Serious events: 17 serious events

Other events: 63 other events

Deaths: 0 deaths

Placebo

Serious events: 23 serious events

Other events: 52 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 (300U) n=89 participants at risk botulinum toxin Type A (300U)	Botulinum Toxin Type A (200U) n=91 participants at risk botulinum toxin Type A (200U)	Placebo n=90 participants at risk Normal saline (placebo)
Gastrointestinal disorders Constipation	6.7% 6/89 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.	5.5% 5/91 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% 2/90 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	6.7% 6/89 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.	3.3% 3/91 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.	6.7% 6/90 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	3.4% 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.	8.8% 8/91 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.	1.1% 1/90 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	1.1% 1/89 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.	6.6% 6/91 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.	3.3% 3/90 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	64.0% 57/89 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.	56.0% 51/91 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.	40.0% 36/90 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 Nasopharyngitis	6.7% 6/89 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.	6.6% 6/91 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.	3.3% 3/90 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 Influenza	1.1% 1/89 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.	5.5% 5/91 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% 0/90 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 Muscle spasms	6.7% 6/89 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.	4.4% 4/91 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.	1.1% 1/90 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	4.5% 4/89 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.	6.6% 6/91 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.	1.1% 1/90 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 Pain in extremity	2.2% 2/89 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.	5.5% 5/91 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.	3.3% 3/90 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 Arthralgia	1.1% 1/89 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.	3.3% 3/91 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.	5.6% 5/90 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	31.5% 28/89 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.	19.8% 18/91 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.	3.3% 3/90 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	10.1% 9/89 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.	5.5% 5/91 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% 4/90 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 Dysuria	7.9% 7/89 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.	5.5% 5/91 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% 2/90 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 incontinence	1.1% 1/89 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.	5.5% 5/91 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% 2/90 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.