NCT03052764: LO-BOT

Evaluation of an Alternative Injection Paradigm for OnabotulinumtoxinA (BOTOX®) in the Treatment of Overactive Bladder in Patients With Urinary Incontinence

Completed Phase 4 Results posted Last updated 24 December 2019

What this trial tests

Phase 4 trial testing onabotulinumtoxinA in Urinary Bladder, Overactive in 120 participants. Completed in 10 December 2018.

Timeline

12 December 2016

Primary endpoint
10 December 2018

10 December 2018

Quick facts

Lead sponsor	Allergan
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	120
Start date	12 December 2016
Primary completion	10 December 2018
Estimated completion	10 December 2018
Sites	31 locations across United States

Drugs / interventions tested

• onabotulinumtoxinA (ONABOTULINUMTOXINA) — full drug profile →
• Placebo (saline)

Conditions studied

• Urinary Bladder, Overactive — all drugs for Urinary Bladder, Overactive →
• Urinary Incontinence — all drugs for Urinary Incontinence →

Sponsor

Allergan — full company profile →

Who can join

18 and older, any sex, with Urinary Bladder, Overactive or Urinary Incontinence. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Daily Average Number of Urinary Incontinence Episodes Primary · Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12

The participant recorded urinary incontinence in a 3-day bladder diary. Data for the three days was averaged. A negative change from Baseline indicates improvement. An analysis of covariance (ANCOVA) model with treatment as a factor at 2 levels, and the number of Urgency Urinary Incontinence (UUI) episodes reported at Baseline (\<= 9 versus \> 9 daily episodes) and Baseline daily average number of episodes of incontinence as covariates was used for analyses.

Group	Value	95% CI
BOTOX® 100 U/BOTOX® 100 U	-2.99	± 0.488
Placebo/BOTOX® 100 U	-0.42	± 0.612

Percentage of Participants Who Achieved Complete Continence Secondary · Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12]

Complete continence is defined as 100% reduction in urinary incontinence from Baseline.

Group	Value	95% CI
BOTOX® 100 U/BOTOX® 100 U	13.9
Placebo/BOTOX® 100 U	2.7

Change From Baseline in Daily Average Number of Micturition Episodes Secondary · Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12

The participant recorded the number of micturition episodes in a 3-day bladder diary. Data for the three days was averaged. A negative change from Baseline indicates improvement. An ANCOVA model with treatment as a factor at 2 levels, and the number of UUI episodes reported at Baseline (\<= 9 versus \> 9 daily episodes) and Baseline daily average number of micturition as covariates was used for analyses.

Group	Value	95% CI
BOTOX® 100 U/BOTOX® 100 U	-2.25	± 0.421
Placebo/BOTOX® 100 U	-0.01	± 0.525

Change From Baseline in Daily Average Number of Urgency Episodes Secondary · Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12

The participant recorded the number of urgency episode in a 3-day bladder diary. Data for the three days was averaged. A negative change from Baseline indicates improvement. An ANCOVA model with treatment as a factor at 2 levels, and the number of UUI episodes reported at Baseline (\<= 9 versus \> 9 daily episodes) and Baseline daily average number of urgency episodes as covariates was used for analyses.

Group	Value	95% CI
BOTOX® 100 U/BOTOX® 100 U	-2.79	± 0.491
Placebo/BOTOX® 100 U	-0.23	± 0.618

Change From Baseline in Daily Average Number of Nocturia Episodes Secondary · Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to, 3 consecutive days prior to Week 12

The participants recorded the number of nocturia episodes in a 3-day bladder diary. Data for the three days was averaged. A negative change from Baseline indicates improvement. An ANCOVA model with treatment as a factor at 2 levels, and the number of UUI episodes reported at Baseline (\<= 9 versus \> 9 daily episodes) and Baseline daily average number of nocturia episodes as covariates was used for analyses.

Group	Value	95% CI
BOTOX® 100 U/BOTOX® 100 U	-0.53	± 0.154
Placebo/BOTOX® 100 U	0.17	± 0.193

Percentage of Participants Who Have a Positive Treatment Response on the Treatment Benefit Scale (TBS) Secondary · Week 12

The participant rated their condition during treatment using the TBS 4-point scale where: 1=greatly improved, 2=improved, 3=not changed or 4=worsened. A positive treatment response is either as score of 1=greatly improved or 2=improved.

Group	Value	95% CI
BOTOX® 100 U/BOTOX® 100 U	74.0
Placebo/BOTOX® 100 U	17.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Randomization to the Study Exit Visit (Up to 70 Weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Double Blind: BOTOX® 100 U

Serious: 5/78 (6%)

Deaths: 0/80

Double Blind: Placebo

Serious: 2/39 (5%)

Deaths: 0/40

Open Label: BOTOX® 100 U/BOTOX® 100 U

Serious: 2/58 (3%)

Deaths: 0/58

Open Label: Placebo/BOTOX® 100 U

Serious: 1/33 (3%)

Deaths: 0/33

Serious adverse events (15 terms)

Reaction	System	Double Blind: BOTOX® 100 U	Double Blind: Placebo	Open Label: BOTOX® 100 U/B…	Open Label: Placebo/BOTOX®…
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Acute coronary syndrome	Cardiac disorders	—	—	—	—
Haematochezia	Gastrointestinal disorders	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—
Post procedural cellulitis	Infections and infestations	—	—	—	—
Pyelonephritis	Infections and infestations	—	—	—	—
Urosepsis	Infections and infestations	—	—	—	—
Breast cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Sciatica	Nervous system disorders	—	—	—	—
Urinary bladder haemorrhage	Renal and urinary disorders	—	—	—	—
Arteriosclerosis coronary artery	Cardiac disorders	—	—	—	—
Chest pain	General disorders	—	—	—	—
Troponin increased	Investigations	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—
Syncope	Nervous system disorders	—	—	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	Double Blind: BOTOX® 100 U	Double Blind: Placebo	Open Label: BOTOX® 100 U/B…	Open Label: Placebo/BOTOX®…
Urinary tract infection	Infections and infestations	—	—	—	—
Dysuria	Renal and urinary disorders	—	—	—	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Most-reported serious reactions: Anaemia, Acute coronary syndrome, Haematochezia, Cellulitis, Post procedural cellulitis, Pyelonephritis, Urosepsis, Breast cancer recurrent.

Data from ClinicalTrials.gov NCT03052764 adverse events section.

Sponsor's own description

This study will evaluate the efficacy and safety of onabotulinumtoxinA 100 U (BOTOX®), compared to placebo, when injected into the bladder using an alternative injection paradigm in reducing the number of daily urinary incontinence episodes in patients with overactive bladder (OAB) and urinary incontinence whose symptoms have not been adequately managed with an anticholinergic.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. 2019 NSAUA Abstracts.
   · 2019 · PMID 31536472 · DOI 10.5489/cuaj.6197