Overactive Bladder Syndrome: Incobotulinumtoxin Versus Onabotulinumtoxin

NCT03758235 | Unknown Phase 3 DMC

• 1 other identifier: Inco_Ona
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the original study was to compare Incobot/A versus Onabot/A in order to evaluate if the differences in the pharmacologic formulations between the two drugs could affect their efficacy and safety in the treatment of neurogenic overactive bladder (OAB). In the original study protocol two different dosages for either Incobot/A and Onabot/A (200 U and 100 U) were considered, to treat patients with neurogenic detrusor overactivity incontinence performing intermittent catheterization (IC) with higher dosages and those able to void spontaneously with lower dosage, with the resulting four treatment groups. For such a study, a very large sample of participants should have been treated and followed up, to have adequate power to demonstrate the hypothesis. At the end of last February 2020, we had to temporarily stop all the clinical activities related to the study and patients' recruitment, due to the occurrence of Sars-Cov-2 pandemic in our Country. At that point, a non-inferiority study seemed to be possible and adequate, and we adapted the protocol accordingly. In addition, on the basis of previously published information, we could hypothesize that the new drug (Incobot/A) would have had at least a roughly similar effect to the control drug (Onabot/A). In order to perform a non-inferiority study, the power and sample size analysis have been re-planned. Thus, we perform a not planned interim analysis to show the preliminary results of an ongoing, non-inferiority trial in which patients' recruitment temporarily stopped due to incontrollable external factors. The present study will be aimed to assess the non-inferiority of Incobot/A compared to Onabot/A on the efficacy and safety parameters, in the treatment of patients with refractory NDOI performing IC, who are randomized to receive 200 U of Incobot/A or Onabot/A intradetrusor injections and who are followed up to 12 wks after treatment

Conditions

Overactive Bladder Syndrome

Keywords

overactive bladder syndrome; botulinum toxin type A; onabotulinumtoxin/A; incobotulinumtoxin/A; treatment; neurogenic detrusor overactivity incontinence; urinary incontinence; urinary tract infections

Outcome Measures

Primary Outcomes (2)

• Change from baseline in the frequency of urinary incontinence episodes.

  change from baseline in the daily frequency of urinary incontinence episodes, as assessed by the 3-day voiding diary.

  24 weeks

• Evaluation of frequency of urinary tract infections in both arms of treatment.

  Measurement of eventual differencies between the two arms of treatment in the frequency of urinary tract infections at 2, 12 and 24 weeks after treatment

  2, 12, 24 weeks

Secondary Outcomes (3)

• Change from baseline in urodynamic parameters.

  24 weeks

• Change from baseline in Incontinence Quality of Life (I-QoL) questionnaire total score.

  2, 12, 24 weeks

• Recording of the adverse events.

  2, 12, 24 weeks

Study Arms (4)

Incobot/A 100 U

EXPERIMENTAL

Incobot/A 100 U diluted in 10 ml of sodium chloride solution 0.9% by endoscopic detrusor injections (20 injections, 0.5 ml of solution for each injection) will be administered in patients able to perform spontaneous micturitions

Drug: IncobotulinumtoxinA 100 UNT Injection [Xeomin]

Incobot/A 200 U

EXPERIMENTAL

Incobot/A 200 U diluted in 30 ml of sodium chloride solution 0.9% by endoscopic detrusor injections (30 injections, 1 ml of solution for each injection) will be administered in patients performin intermittent catheterization.

Drug: IncobotulinumtoxinA 100 UNT Injection [Xeomin]

Onabot/A 100 U

ACTIVE COMPARATOR

Onabot/A 100 U diluted in 10 ml of sodium chloride solution 0.9% by endoscopic detrusor injections (20 injections, 0.5 ml of solution for each injection) will be administered in patients able to perform spontaneous micturitions

Drug: OnabotulinumtoxinA 100 UNT [Botox]

Onabot/A 200 U

ACTIVE COMPARATOR

Onabot/A 200 U diluted in 30 ml of sodium chloride solution 0.9% by endoscopic detrusor injections (30 injections, 1 ml of solution for each injection) will be administered to patients performing intermittent catheterization

Drug: OnabotulinumtoxinA 100 UNT [Botox]

Interventions

IncobotulinumtoxinA 100 UNT Injection [Xeomin] DRUG

Incobot/A intradetrusor injections under cystscopic guidance, with local anaethesia in an outpatient basis

Also known as: Incobot/A

Incobot/A 100 U; Incobot/A 200 U

OnabotulinumtoxinA 100 UNT [Botox] DRUG

Onabot/A intradetrusor injections under cystscopic guidance, with local anaethesia in an outpatient basis

Also known as: Onabot/A

Onabot/A 100 U; Onabot/A 200 U

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients (males and females) with neurogenic urge urinary incontinence (UUI) (with urgency, increase in day- time and night- time urinary frequency) and with urodynamic diagnosis of DO;
• years;
• women of childbearing age, who use a reliable method of contraception throughout the study period (a pregnancy test must be performed during enrolment in the study);
• spinal cord injury at or below T1, diagnosed at least 6 months before the screening in case of a vesico-sphincter dysfunction due to spinal cord injury;
• EDSS score ≤ 6, in MS patients;
• patients refractory to anticholinergic therapy (≥ 1 anticholinergic agent)
• application of intermittent catheterizations to empty the bladder. In the case of spontaneous micturition, the patients should agree for the use of intermittent catheterizations, in case this will be necessary after treatment with the detrusor injection of botulinumtoxin A.

You may not qualify if:

• recurring urinary tract infections (UTIs) (≥ 4 episodes/year);
• spinal cord injuries above T1;
• MS patients: EDSS score ≥ 6;
• patients who won't or can't perform intermittent catheterization;
• pregnancy or breast- feeding, if female patients;
• post- void residual volume (PRV) \> 150 ml, in the case of spontaneous micturition;
• hypersensitivity to the active substance or to any of the excipients (listed in section 6.1 of RCP);
• generalized diseases of muscular activity (e.g. myasthenia gravis, Lambert-Eaton syndrome);
• presence of infection or inflammation at the injection site;
• patients with acute urinary retention at the time of treatment, not routinely subjected to catheterization;
• men with overactive bladder and signs or symptoms of urinary obstruction should not be treated;
• documented or suspected active malignant neoplasia or previous history, within 2 years prior to screening;
• patients who must or want to continue taking illegal drugs or drugs that may interfere with the proper conduct of the study;
• chronic abuse of alcohol or drugs or any condition that in the opinion of the investigator doctor makes an unreliable subject in correctly completing the study procedures;
• any other clinical condition that would endanger the safety of patients in participating in the study or that could prevent the subjects from adhering to the protocol.

Sponsors & Collaborators

• University Of Perugia: lead

Study Sites (1)

Antonella Giannantoni

Siena, SI, 53100, Italy

Location

Related Publications (20)

• Mohee A, Khan A, Harris N, Eardley I. Long-term outcome of the use of intravesical botulinum toxin for the treatment of overactive bladder (OAB). BJU Int. 2013 Jan;111(1):106-13. doi: 10.1111/j.1464-410X.2012.11282.x. Epub 2012 Jun 6.

  PMID: 22672569 BACKGROUND

• Thuroff JW, Abrams P, Andersson KE, Artibani W, Chapple CR, Drake MJ, Hampel C, Neisius A, Schroder A, Tubaro A. EAU guidelines on urinary incontinence. Eur Urol. 2011 Mar;59(3):387-400. doi: 10.1016/j.eururo.2010.11.021. Epub 2010 Nov 24.

  PMID: 21130559 RESULT

• Gormley EA, Lightner DJ, Faraday M, Vasavada SP; American Urological Association; Society of Urodynamics, Female Pelvic Medicine. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol. 2015 May;193(5):1572-80. doi: 10.1016/j.juro.2015.01.087. Epub 2015 Jan 23.

  PMID: 25623739 RESULT

• Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, van Kerrebroeck P, Victor A, Wein A; Standardisation Sub-committee of the International Continence Society. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn. 2002;21(2):167-78. doi: 10.1002/nau.10052. No abstract available.

  PMID: 11857671 RESULT

• Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, Monga A, Petri E, Rizk DE, Sand PK, Schaer GN; International Urogynecological Association; International Continence Society. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn. 2010;29(1):4-20. doi: 10.1002/nau.20798.

  PMID: 19941278 RESULT

• Lemack GE, Dewey RB Jr, Roehrborn CG, O'Suilleabhain PE, Zimmern PE. Questionnaire-based assessment of bladder dysfunction in patients with mild to moderate Parkinson's disease. Urology. 2000 Aug 1;56(2):250-4. doi: 10.1016/s0090-4295(00)00641-5.

  PMID: 10925088 RESULT

• Aharony SM, Lam O, Corcos J. Evaluation of lower urinary tract symptoms in multiple sclerosis patients: Review of the literature and current guidelines. Can Urol Assoc J. 2017 Jan-Feb;11(1-2):61-64. doi: 10.5489/cuaj.4058.

  PMID: 28443147 RESULT

• Wyndaele JJ. The management of neurogenic lower urinary tract dysfunction after spinal cord injury. Nat Rev Urol. 2016 Dec;13(12):705-714. doi: 10.1038/nrurol.2016.206. Epub 2016 Oct 25.

  PMID: 27779229 RESULT

• Campos-Sousa RN, Quagliato E, da Silva BB, de Carvalho RM Jr, Ribeiro SC, de Carvalho DF. Urinary symptoms in Parkinson's disease: prevalence and associated factors. Arq Neuropsiquiatr. 2003 Jun;61(2B):359-63. doi: 10.1590/s0004-282x2003000300007. Epub 2003 Jul 28.

  PMID: 12894267 RESULT

• Kanai A, Andersson KE. Bladder afferent signaling: recent findings. J Urol. 2010 Apr;183(4):1288-95. doi: 10.1016/j.juro.2009.12.060. Epub 2010 Feb 19.

  PMID: 20171668 RESULT

• Veenboer PW, Bosch JL. Long-term adherence to antimuscarinic therapy in everyday practice: a systematic review. J Urol. 2014 Apr;191(4):1003-8. doi: 10.1016/j.juro.2013.10.046. Epub 2013 Oct 16.

  PMID: 24140548 RESULT

• Di Stasi SM, Giannantoni A, Vespasiani G, Navarra P, Capelli G, Massoud R, Stephen RL. Intravesical electromotive administration of oxybutynin in patients with detrusor hyperreflexia unresponsive to standard anticholinergic regimens. J Urol. 2001 Feb;165(2):491-8. doi: 10.1097/00005392-200102000-00032.

  PMID: 11176403 RESULT

• Jost WH, Benecke R, Hauschke D, Jankovic J, Kanovsky P, Roggenkamper P, Simpson DM, Comella CL. Clinical and pharmacological properties of incobotulinumtoxinA and its use in neurological disorders. Drug Des Devel Ther. 2015 Apr 1;9:1913-26. doi: 10.2147/DDDT.S79193. eCollection 2015.

  PMID: 25897202 RESULT

• Veeratterapillay R, Harding C, Teo L, Vasdev N, Abroaf A, Dorkin TJ, Pickard RS, Hasan T, Thorpe AC. Discontinuation rates and inter-injection interval for repeated intravesical botulinum toxin type A injections for detrusor overactivity. Int J Urol. 2014 Feb;21(2):175-8. doi: 10.1111/iju.12205. Epub 2013 Jul 2.

  PMID: 23819724 RESULT

• Frevert J. Response to Commentary by W. Jost on: Pharmaceutical, Biological, and Clinical Properties of Botulinum Neurotoxin Type A Products. Drugs R D. 2015 Jun;15(2):217-8. doi: 10.1007/s40268-015-0091-y. No abstract available.

  PMID: 25851380 RESULT

• Benecke R. Clinical relevance of botulinum toxin immunogenicity. BioDrugs. 2012 Apr 1;26(2):e1-9. doi: 10.2165/11599840-000000000-00000.

  PMID: 22385408 RESULT

• Wang L, Sun Y, Yang W, Lindo P, Singh BR. Type A botulinum neurotoxin complex proteins differentially modulate host response of neuronal cells. Toxicon. 2014 May;82:52-60. doi: 10.1016/j.toxicon.2014.02.004. Epub 2014 Feb 21.

  PMID: 24560879 RESULT

• Jost WH, Blumel J, Grafe S. Botulinum neurotoxin type A free of complexing proteins (XEOMIN) in focal dystonia. Drugs. 2007;67(5):669-83. doi: 10.2165/00003495-200767050-00003.

  PMID: 17385940 RESULT

• Kumar R, Zhou Y, Ghosal K, Cai S, Singh BR. Anti-apoptotic activity of hemagglutinin-33 and botulinum neurotoxin and its implications to therapeutic and countermeasure issues. Biochem Biophys Res Commun. 2012 Jan 13;417(2):726-31. doi: 10.1016/j.bbrc.2011.12.020. Epub 2011 Dec 11.

  PMID: 22182409 RESULT

• Campanati A, Giuliodori K, Martina E, Giuliano A, Ganzetti G, Offidani A. Onabotulinumtoxin type A (Botox((R))) versus Incobotulinumtoxin type A (Xeomin((R))) in the treatment of focal idiopathic palmar hyperhidrosis: results of a comparative double-blind clinical trial. J Neural Transm (Vienna). 2014 Jan;121(1):21-6. doi: 10.1007/s00702-013-1074-1. Epub 2013 Sep 20.

  PMID: 24052109 RESULT

MeSH Terms

Conditions

Urinary Incontinence; Urinary Tract Infections

Interventions

incobotulinumtoxinA; Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infections

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Antonella Giannantoni, M.D.

  University of Siena

  PRINCIPAL INVESTIGATOR

• Emanuele Rubilotta, MD

  Universita di Verona

  STUDY CHAIR

• Matteo Balzarro, MD

  Universita di Verona

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Partecipants, investigators and outcomes assessor
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PA

Model Details: Participants are assigned to the 4 groups (Incobot/A Group different dosages, or Onabot/A Group different dosages ) in parallel for the duration of the study.

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: November 29, 2018
• Study Start: September 1, 2018
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: November 6, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)