OnabotulinumtoxinA (onaBoNT-A) Versus Oral Oxybutynin ER

NCT01050114 | Unknown Phase 3 DMC

• 2 other identifiers: 11-09-10-04 (BCM H-26296)H-26296
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

Overactive bladder is a condition associated with symptoms of feeling the urge to urinate, urinating often, and may or may not be accompanied by leakage of urine. A patient who has a spinal cord injury (SCI) often suffers from an overactive bladder which often leads to urinary incontinence (UI - an unwanted leakage of urine). OnaBoNT-A bladder injections have been studied in clinical research trials. The results have shown an improvement in urinary symptoms by reducing how often urine leakage occurs and by increasing the amount of urine the bladder can hold. This purpose of this clinical trial is to see if onaBoNT-A is safe and effective when injected into the bladder for the treatment of UI and if it works better than a drug that is taken by mouth. A second purpose of the study is to perform research tests on the urine samples provided by the volunteers. Urine presents a rich source of information for bladder diseases and the biomarkers (the chemical make-up of the urine cells) will be examined to learn if there are yet undiscovered reasons for urinary diseases. These tests would be very beneficial because the results would lead to better treatment of the urinary diseases. Volunteers will be randomized to either: ARM 1: onaBoNT-A 200 U bladder injection and placebo oral capsule daily or ARM 2: Placebo bladder injection (saline) and oxybutynin ER 10mg capsule twice a day. The treatments are onaBoNT-A bladder injection and a placebo oral capsule once a day or placebo bladder injection and oxybutynin ER (like Ditropan) capsule twice a day. Placebo contains no active medicine. Participation in this study will be about 6-7 months and involve 5 visits to the clinic. The risks of bladder onaBoNT-A

Conditions

Overactive Bladder

Keywords

Botulinum Toxin; Oxybutynin; Overactive Bladder; Spinal Cord Injury; Urinary Incontinence; Nerve Growth Factor; Urine Biomarkers

Outcome Measures

Primary Outcomes (1)

• Primary endpoint

  The primary endpoint is the reduction in mean weekly incontinent episodes in the onaBoNT-A treated group compared to the oxybutynin treated group at 12 weeks.

  12 weeks

Secondary Outcomes (1)

• The utility of urinary inflammatory markers as statistically significant predictors of treatment response.

  30 weeks

Study Arms (2)

ARM 1: onaBoNT-A injection + placebo

OTHER

onaBoNT-A 200 U (treatment 1)/ onaBoNT-A 200 U (treatment 2)/ onaBoNT-A 200 U (treatment 3) and placebo oral capsule daily

Drug: onaBoNT-A

ARM 2: Placebo injection + oxybutynin ER

OTHER

Placebo injection (treatment 1)/ onaBoNT-A 200 U (treatment 2)/ onaBoNT-A 200 U (treatment 3) and oxybutynin ER 10 mg capsule daily

Drug: Oxybutynin ER

Interventions

onaBoNT-A DRUG

onaBoNT-A will be the active formulation. Each vial of onaBoNT-A Purified Neurotoxin Complex, Formulation No. 9060X, contains: 100 units (U) of Clostridium botulinum toxin type A, 0.5 mg albumin (human), and 0.9 mg sodium chloride in a sterile, vacuum-dried form without a preservative. One U corresponds to the calculated median lethal intraperitoneal dose (LD50) in mice. A 0.9% sterile saline (without preservative) for injection will be used as diluent for onaBoNT-A. Each treatment session will be administered as 20 injections each of 1 mL (10U/ml), evenly distributed into the bladder.

Also known as: onabotulinumtoxinA, BOTOX(R)

ARM 1: onaBoNT-A injection + placebo

Oxybutynin ER DRUG

Oxybutynin ER in a 10 mg capsule will be taken twice a day for the course of the study.

Also known as: Ditropan XL, Urotrol, Oxytrol

ARM 2: Placebo injection + oxybutynin ER

Eligibility Criteria

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

You may qualify if:

• male or female, aged 18 to 80 years old, weighing 110 pounds or more.
• urinary incontinence as a result of neurogenic detrusor overactivity for a period of at least 3 months prior to screening as a result of spinal cord injury
• must have a stable neurological injury occurring at least 6 months or more.
• has detrusor overactivity demonstrated during the screening period or within 1 year of screening.
• has a negative pregnancy result if female and of childbearing potential.
• The following criteria are also required for entry into the study at Randomization/Day 1:
• experiences at least 14 episodes or more of urinary incontinence per week with no more than 2 incontinent-free days.
• currently uses or is willing to use clean intermittent catheterization (CIC) to empty the bladder (indwelling catheter is not permitted).
• Volunteers with a negative urine culture result must take an antibiotic medication for 3 days immediately prior to Randomization/Day 1 and agree to continue antibiotic medication for at least 3 days following treatment. Volunteers with a positive urine culture result indicating urinary tract infection (UTI), must take an antibiotic to which the identified organism is sensitive for at least 3 days immediately prior to Randomization/Day 1, on Randomization/Day 1, and continue for 3 days following the procedure (or longer as needed).

You may not qualify if:

• has history or evidence of any pelvic or urological abnormalities including but not limited to the following:
• elevated serum creatinine more than 2 times the upper limit of normal (reference range)
• current or history of hematuria, 1) if the hematuria is determined to be a pathologic condition or 2) is uninvestigated
• interstitial cystitis in the opinion of the investigator bladder stones within 6 months of screening
• surgery or bladder disease other than detrusor overactivity that may impact bladder function with the exception of surgeries for bladder stones (more than 6 months) and stress incontinence, uterine prolapse, rectocele, or cystocele (more than1year) from screening.
• has had previous or current botulinum toxin therapy within 9 months.
• has been immunized for any botulinum toxin serotype.
• discontinued anticholinergic medication for overactive bladder less than 14 days prior to Randomization/Day 1.
• has a history or current diagnosis of bladder cancer.
• male with previous or current diagnosis of prostate cancer or has a Prostate Specific Antigen (PSA) level greater than 10.0 ng/mL.
• has 24 hour total volume voided more than 3000 mL of urine
• has a post void residual volume above 200 mL.
• has an active genital infection, other than genital warts, either concurrently or within 4 weeks prior to screening.
• uses any anti-platelet or anticoagulant therapy or is using medications with anticoagulative effects within 3 days prior to treatment.
• has hemophilia or other clotting factor deficiencies or disorders that cause bleeding diatheses.

Sponsors & Collaborators

• Christopher Patrick Smith: lead

Study Sites (2)

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

TIRR-Memorial Hermann

Houston, Texas, 77030, United States

NOT YET RECRUITING

Related Publications (5)

• O'Leary M, Erickson JR, Smith CP, McDermott C, Horton J, Chancellor MB. Effect of controlled-release oxybutynin on neurogenic bladder function in spinal cord injury. J Spinal Cord Med. 2003 Summer;26(2):159-62. doi: 10.1080/10790268.2003.11753678.

  PMID: 12828295 BACKGROUND

• Smith CP, Chancellor MB. Emerging role of botulinum toxin in the management of voiding dysfunction. J Urol. 2004 Jun;171(6 Pt 1):2128-37. doi: 10.1097/01.ju.0000127725.48479.89.

  PMID: 15126771 BACKGROUND

• Smith CP, Nishiguchi J, O'Leary M, Yoshimura N, Chancellor MB. Single-institution experience in 110 patients with botulinum toxin A injection into bladder or urethra. Urology. 2005 Jan;65(1):37-41. doi: 10.1016/j.urology.2004.08.016.

  PMID: 15667859 BACKGROUND

• Liu HT, Tyagi P, Chancellor MB, Kuo HC. Urinary nerve growth factor but not prostaglandin E2 increases in patients with interstitial cystitis/bladder pain syndrome and detrusor overactivity. BJU Int. 2010 Dec;106(11):1681-5. doi: 10.1111/j.1464-410X.2009.08851.x.

  PMID: 19751258 BACKGROUND

• Tyagi P, Barclay D, Zamora R, Yoshimura N, Peters K, Vodovotz Y, Chancellor M. Urine cytokines suggest an inflammatory response in the overactive bladder: a pilot study. Int Urol Nephrol. 2010 Sep;42(3):629-35. doi: 10.1007/s11255-009-9647-5. Epub 2009 Sep 26.

  PMID: 19784793 BACKGROUND

MeSH Terms

Conditions

Urinary Bladder, Overactive; Spinal Cord Injuries; Urinary Incontinence; Hereditary Sensory and Autonomic Neuropathies

Interventions

onabotulinum toxin A; Botulinum Toxins, Type A; Tolterodine Tartrate; oxybutynin

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; 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; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Urination Disorders; Nervous System Malformations; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

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; Phenylpropanolamine; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Cresols; Phenols

Study Officials

• Christopher P. Smith, MD

  Baylor College of Medicine

  STUDY DIRECTOR

Central Study Contacts

Sebrina Tello

CONTACT

713-798-8106; stello@bcm.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 11, 2010
• First Posted: January 15, 2010
• Study Start: August 1, 2013
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: August 30, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)