Nitti OAB Trial: OnabotulinumtoxinA 100 U for Overactive Bladder with Urinary Incontinence
The Nitti OAB Trial (Allergan study 191622-095) was a multicenter, double-blind, placebo-controlled phase 3 randomized trial of intradetrusor onabotulinumtoxinA 100 U versus placebo in 557 patients with overactive bladder and urgency urinary incontinence inadequately managed with anticholinergics. At week 12, daily incontinence episodes fell by 2.65 with onabotulinumtoxinA and 0.87 with placebo, and 60.8% versus 29.2% reported a positive treatment benefit scale response (both P < 0.001).[1][2][3]
- Design and population
- Multicenter, double-blind, placebo-controlled phase 3 randomized trial. Adults with idiopathic overactive bladder, at least 3 urgency incontinence episodes in 3 days and at least 8 micturitions a day, inadequately managed with anticholinergics.
- Arms
- Intradetrusor onabotulinumtoxinA 100 U versus intradetrusor saline placebo
- Report and follow-up
- 2012 · Week 12 primary endpoints within a 24-week placebo-controlled cycle
| Endpoint | Results | Effect | Finding |
|---|---|---|---|
| Mean change from baseline in daily urinary incontinence episodes at week 12 (coprimary); difference is the ANCOVA least-squares mean difference, onabotulinumtoxinA minus placebo | −2.65 vs −0.87 | difference -1.6; 95% -2.1–-1.2; P <0.001 | Met |
| Proportion with a positive response on the treatment benefit scale at week 12 (coprimary) | 60.8% vs 29.2% | P <0.001 | Met |
| Median duration of response by qualification for retreatment (pooled Study OAB-1 and OAB-2) | 19 to 24 weeks vs 13 weeks | — | Descriptive |
Harms: Urinary tract infection: 68/278 (24.5%) vs 25/272 (9.2%); Urinary retention: 16/278 (5.8%) vs 1/272 (0.4%); Dysuria: 40/278 (14.4%) vs 27/272 (9.9%)
Design
Eligible patients had overactive bladder with at least 3 urgency incontinence episodes in 3 days and at least 8 micturitions a day, and an inadequate response to or intolerable side effects from anticholinergics.[1][2] The registry lists age 18 years or older and symptoms for at least 6 months, and excludes overactive bladder caused by a neurologic condition, stress-predominant incontinence, and any history or evidence of pelvic or urologic abnormality.[3]
Patients were randomized 1:1 to 280 onabotulinumtoxinA and 277 placebo; 252/280 (90.0%) and 245/277 (88.4%) were women, and 121 (43.2%) and 117 (42.2%) were 65 or older. Baseline mean daily incontinence episodes were 5.47 and 5.09, and daily micturitions 11.98 and 11.20.[1][3]
The coprimary endpoints were the change in daily urinary incontinence episodes (3-day bladder diary) and the proportion with a positive response on the treatment benefit scale, both at week 12. Secondary endpoints included other overactive bladder symptoms and health-related quality of life.[1][3] The FDA label describes the primary analysis as an ANCOVA with the last observation carried forward.[2]
Results
Daily incontinence episodes changed by −2.65 with onabotulinumtoxinA and −0.87 with placebo (P < 0.001). In the FDA label's analysis of this study, the least-squares mean difference was −1.6 episodes per day (95% CI −2.1 to −1.2).[1][2][3] A positive treatment benefit scale response occurred in 60.8% versus 29.2% (P < 0.001), and 22.9% versus 6.5% became completely continent. Both coprimary endpoints favored onabotulinumtoxinA.[1]
Daily micturitions changed by −1.9 versus −0.9 (difference −1.0; 95% CI −1.5 to −0.6) and volume voided per micturition rose by 38 versus 8 mL (difference 30 mL; 95% CI 17 to 43), both P < 0.001.[2] The report states that all other overactive bladder symptoms improved (P ≤ 0.05) and that health-related quality of life improved across multiple measures (P < 0.001).[1]
Across both pivotal trials, the median duration of response by retreatment qualification was 19 to 24 weeks with 100 U and 13 weeks with placebo.[2] Patients who completed either trial could enter a 3-year extension with as-needed retreatment; outcomes are reported for 100 U treatments 1 to 6.[4] Mean change in daily incontinence episodes at week 12 ranged from −3.1 to −3.8 across treatments 1 to 6, the median duration of effect was 7.6 months, and de novo catheterization occurred in 4.0% after the first treatment and 0.6% to 1.7% after later treatments.[4]
Surgery and treatment delivery
Each patient received 20 intradetrusor injections of 5 U (onabotulinumtoxinA or placebo) about 1 cm apart, 100 U in total.[2] The AUA/SUFU guideline states that the placebo-controlled trials in its evidence base, which include this one, used trigone-sparing injection.[5]
A repeat injection of 100 U after at least 12 weeks was permitted where applicable, and placebo recipients received onabotulinumtoxinA in the second cycle.[3] Retreatment required at least 12 weeks since the prior injection, a post-void residual below 200 mL and at least 2 incontinence episodes over 3 days; the median time to qualify in the two placebo-controlled studies was 169 days.[2] In cycle 1, 249/280 (88.9%) and 243/277 (87.7%) completed the phase, and 141 and 212 patients entered cycle 2.[3]
The FDA label for the OAB indication specifies 100 U in 10 mL of nonpreserved saline through a flexible or rigid cystoscope, with the trigone and bladder overdistension avoided, a needle depth of about 2 mm, 20 injections of 0.5 mL about 1 cm apart, and observation for at least 30 minutes and until a spontaneous void. It requires no urinary tract infection at treatment, antibiotic prophylaxis (not aminoglycosides) from 1 to 3 days before to 1 to 3 days after the injection, and discontinuing antiplatelet therapy at least 3 days beforehand.[2]
Adverse events
In the registry's placebo-controlled safety population (278 onabotulinumtoxinA, 272 placebo) at any time in treatment cycle 1, urinary tract infection occurred in 68 (24.5%) versus 25 (9.2%), urinary retention in 16 (5.8%) versus 1 (0.4%), dysuria in 40 (14.4%) versus 27 (9.9%), bacteriuria in 23 (8.3%) versus 10 (3.7%), and hematuria in 8 (2.9%) versus 16 (5.9%). Serious adverse events affected 18 (6.5%) and 16 (5.9%). The trial report gives a urinary retention rate of 5.4% (15/278) within the first 12 weeks.[1][3]
Pooled across both pivotal trials, urinary tract infection within 12 weeks affected 99/552 (18%) versus 30/542 (6%), and catheterization for retention was started in 36/552 (6.5%) versus 2/542 (0.4%) at any time in the treatment cycle. Median catheterization lasted 63 days (range 1 to 214) after onabotulinumtoxinA and 11 days (range 3 to 18) after placebo.[2]
In the pooled pivotal trials, diabetes was associated with more retention and infection after onabotulinumtoxinA: retention in 10/81 (12.3%) with diabetes versus 33/526 (6.3%) without, and urinary tract infection in 25/81 (31%) versus 135/526 (26%). Among pooled onabotulinumtoxinA recipients, infection occurred in 44% of those whose maximum post-void residual exceeded 200 mL and 23% of those below 200 mL.[2]
Limitations
The comparator was placebo and the primary endpoints were measured at week 12 of a 24-week cycle, so the trial does not compare onabotulinumtoxinA with another third-line therapy or measure durability against a control. The population was 89.2% women (497/557), and the trial excluded neurogenic overactive bladder, stress-predominant incontinence and pelvic or urologic abnormality.[3] The sponsor was Allergan.[3]
The 3.5-year extension was open label and uncontrolled and pooled patients from both trials.[4]
In conversation
- Parallel to Ginsberg NDO (2012). Same drug and sponsor, placebo-controlled phase 3 design; Ginsberg studied neurogenic detrusor overactivity at higher doses, this trial idiopathic OAB at 100 U.
- Parallel to ABC (2012). Both tested 100 U onabotulinumtoxinA in idiopathic overactive bladder with urgency incontinence; ABC used an anticholinergic comparator rather than placebo.
- Parallel to Ginsberg NDO (2012). Same toxin and route tested in idiopathic OAB at 100 U; this trial used 200 U and 300 U in neurogenic detrusor overactivity.
Same setting ROSETTA (2016)
The ABC trial compared onabotulinumtoxinA with oral anticholinergic therapy and ROSETTA compared it with sacral neuromodulation; neither used a placebo, and their populations, doses and endpoints differ, so their incontinence-episode changes are not interchangeable with the placebo-controlled differences here.
Guidelines and approvals
- AUA/SUFU (Idiopathic Overactive Bladder, 2024), statement 25. In patients with overactive bladder who have an inadequate response to or intolerable side effects from pharmacotherapy or behavioral therapy, clinicians should offer sacral neuromodulation, percutaneous tibial nerve stimulation and/or intradetrusor botulinum toxin injection . The guideline cites this trial among four placebo-controlled randomized trials of botulinum toxin.[5]
- AUA/SUFU (2024), statement 26. Clinicians should measure post-void residual in patients with overactive bladder before intradetrusor botulinum toxin injection ; the guideline notes that the trials in its evidence base, including this one, used a post-void residual exclusion threshold in the 100 to 200 mL range.[5]
- EAU (Non-Neurogenic Female LUTS, limited update March 2026). Offer bladder wall injections of onabotulinumtoxinA (100 U) to patients with overactive bladder or urgency urinary incontinence refractory to conservative therapy or drug treatment , and warn patients of the limited duration of response, risk of urinary tract infection and possible prolonged need for intermittent catheterization . The guideline cites this trial for the adverse events in the regulatory trials.[6]
- FDA (January 18, 2013). OnabotulinumtoxinA was approved for overactive bladder with symptoms of urinary incontinence, urgency and frequency in adults who have had an inadequate response to or are intolerant of an anticholinergic medication; the labeled dose is 100 U.[7][2]
Report history
| Published | Report | Cutoff | Headline results | Citation |
|---|---|---|---|---|
| 2012-12-14 | Phase 3 randomized report · primary | — | Mean change from baseline in daily urinary incontinence episodes at week 12 (coprimary); difference is the ANCOVA least-squares mean difference, onabotulinumtoxinA minus placebo: −2.65 vs −0.87; difference -1.6; 95% -2.1–-1.2; P <0.001 Met Proportion with a positive response on the treatment benefit scale at week 12 (coprimary): 60.8% vs 29.2%; P <0.001 Met Proportion completely continent at week 12: 22.9% vs 6.5%; — Mean change from baseline in daily micturition episodes at week 12; least-squares mean change and difference, onabotulinumtoxinA minus placebo: −1.9 vs −0.9; difference -1; 95% -1.5–-0.6; P <0.001 Mean change from baseline in volume voided per micturition (mL) at week 12; least-squares mean change and difference, onabotulinumtoxinA minus placebo: +38 mL vs +8 mL; difference 30; 95% 17–43; P <0.001 All other overactive bladder symptoms, week 12 versus placebo: —; P ≤0.05 Health-related quality of life across multiple measures, week 12: —; P <0.001 Median duration of response by qualification for retreatment (pooled Study OAB-1 and OAB-2): 19 to 24 weeks vs 13 weeks; — Descriptive | Nitti VW, Dmochowski R, Herschorn S, et al. "OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled Trial." *J Urol.* 2013;189(6):2186-2193. doi:10.1016/j.juro.2012.12.022 DOI |
| 2016-03-30 | 3.5-year extension · updated | — | Mean change from baseline in daily incontinence episodes at week 12 after each treatment, overall population (range across up to 6 treatments): −3.1 to −3.8; — Descriptive Median duration of effect: 7.6 months; — Descriptive | Nitti VW, Ginsberg D, Sievert KD, et al. "Durable Efficacy and Safety of Long-Term OnabotulinumtoxinA Treatment in Patients with Overactive Bladder Syndrome: Final Results of a 3.5-Year Study." *J Urol.* 2016;196(3):791-800. doi:10.1016/j.juro.2016.03.146 DOI |
References
1. Nitti VW, Dmochowski R, Herschorn S, et al. "OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled Trial." J Urol. 2013;189(6):2186-2193. doi:10.1016/j.juro.2012.12.022
2. U.S. Food and Drug Administration. BOTOX (onabotulinumtoxinA) prescribing information. BLA 103000/S-5251; revised January 2013. Sections 2.3 and 14.1, Tables 6, 7, 10, 11 and 16.
3. ClinicalTrials.gov. Study of Botulinum Toxin Type A for the Treatment of Patients With Idiopathic Overactive Bladder With Urinary Incontinence. NCT00910845 (Allergan 191622-095). Results posted March 2013.
4. Nitti VW, Ginsberg D, Sievert KD, et al. "Durable Efficacy and Safety of Long-Term OnabotulinumtoxinA Treatment in Patients with Overactive Bladder Syndrome: Final Results of a 3.5-Year Study." J Urol. 2016;196(3):791-800. doi:10.1016/j.juro.2016.03.146
5. Cameron AP, Chung DE, Dielubanza EJ, et al. "The AUA/SUFU Guideline on the Diagnosis and Treatment of Idiopathic Overactive Bladder." J Urol. 2024;212(1):11-20. doi:10.1097/JU.0000000000003985
6. Harding CK, Lapitan MC, Arlandis S, et al. EAU Guidelines on Management of Non-Neurogenic Female Lower Urinary Tract Symptoms (LUTS). Limited update March 2026. European Association of Urology; 2026. Sections 4.1.4.c.1 and 4.1.4.c.1.a.
7. U.S. Food and Drug Administration. BOTOX (onabotulinumtoxinA) supplemental approval letter, sBLA 103000/5251. January 18, 2013.