Mirabegron and Oxybutynin Safety and Efficacy Trial in Spinal Cord Injury

NCT03187795 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: D-961-17
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine the effectiveness and safety of mirabegron compared to oxybutynin chloride immediate release (oxybutynin IR) for a condition called neurogenic detrusor overactivity in individuals with chronic spinal cord injury (SCI).

Conditions

Spinal Cord Injuries; Urinary Bladder, Neurogenic

Keywords

Spinal Cord Injuries; Randomized Controlled Trial; Neurogenic Bladder; Rehabilitation

Outcome Measures

Primary Outcomes (1)

• Change in cystometric bladder capacity during filing cystometry

  The cystometric bladder capacity is the bladder volume (ml) at the end of the filling cystometrogram, when 'permission to void' is usually given.

  Week 6 and Week 12

Secondary Outcomes (13)

• Change in detrusor leak point pressure

  Week 6 and Week 12

• Change in maximum detrusor pressure

  Week 6 and Week 12

• Change in bladder compliance during filling cystometry

  Week 6 and Week 12

• Change in post-void residual volume

  Week 6 and Week 12

• Change on International Lower Urinary Tract Function Basic Spinal Cord Injury (SCI) Data Set

  Week 6 and Week 12

Other Outcomes (2)

• Adverse Event Case Report Form

  Every two weeks for 12 weeks

• Side Effects Record

  Every two weeks for 12 weeks

Study Arms (2)

Oxybutynin chloride IR then Mirabegron

EXPERIMENTAL

Subjects randomized to this group will receive oxybutynin IR (5 mg three times daily) for 6 weeks. After the initial 6 weeks, subjects in this group will then be switched to an escalating dose of mirabegron for 6 weeks (25 mg once daily for 2 weeks, followed by 50 mg once daily for 4 weeks; Note: two placebo daily will be included with mirabegron once daily to match the frequency of dosing to oxybutynin IR three times daily).

Drug: Oxybutynin Chloride IR; Drug: Mirabegron

Mirabegron then Oxybutynin chloride IR

EXPERIMENTAL

Subjects randomized to this group will receive an escalating dose of mirabegron for 6 weeks (25 mg once daily for 2 weeks, followed by 50 mg once daily for 4 weeks; Note: two placebo daily will be included with mirabegron once daily to match the frequency of dosing to oxybutynin IR three times daily). After the initial 6 weeks, subjects in this group will then be switched to receive oxybutynin IR (5 mg three times daily) for 6 weeks

Drug: Oxybutynin Chloride IR; Drug: Mirabegron

Interventions

Oxybutynin Chloride IR DRUG

Oxybutynin chloride immediate release (IR) 5 mg three times daily for 6 weeks

Also known as: Ditropan

Mirabegron then Oxybutynin chloride IR; Oxybutynin chloride IR then Mirabegron

Mirabegron DRUG

Mirabegron 25 mg tablet once daily for 2 weeks, followed by mirabegron 50 mg once daily for 4 weeks (Note: Placebo twice daily will be included with mirabegron once daily to match the three-time daily dosing of oxybutynin IR in the other intervention).

Also known as: Myrbetriq

Mirabegron then Oxybutynin chloride IR; Oxybutynin chloride IR then Mirabegron

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has a neurological impairment secondary to a traumatic spinal cord injury that occurred at least twelve (12) months prior to the screening visit.
• The injury is classified as complete or incomplete (AIS grade A-D) and the neurological level of the injury is above T12.
• The subject's method of bladder management is intermittent catheterization (IC) or indwelling catheter (transurethral or suprapubic).
• There is urodynamic documentation of neurogenic detrusor overactivity (NDO).
• The subject is on a stable dose of oxybutynin IR three times daily.
• The subject is able and willing to comply with the study protocol, including availability for all scheduled clinic visits and locomotor training sessions.
• The subject is able to and has voluntarily given informed consent prior to the performance of any study-specific procedures.

You may not qualify if:

• The subject has taken mirabegron within one month of the Screening Visit.
• The subject has received a botulinum toxin injection to the bladder within one year of the Screening Visit.
• The subject is allergic to mirabegron.
• The subject has a history of uncontrolled autonomic dysreflexia or significant autonomic dysreflexia on urodynamics (systolic BP≥150 mm/Hg).
• The subject has a known history of significant anatomical problems of the upper tracts, including hydronephrosis, kidney stones, or ureteropelvic junction obstruction.
• The subject has a known history or treatment for a non-neurogenic bladder or prostate problem (prostate cancer, bladder cancer).
• The subject has recurrent UTIs, defined as a UTI more than every three months.
• The subject has untreated Grade 3 or above vesicoureteral reflux.
• If female, the subject is pregnant (documented by a urine pregnancy test) or breastfeeding.
• The subject has taken another investigational drug within 30 days before screening.
• The subject has a medical condition that might pose a safety issue or would interfere with interpretation of study results or study conduct.

Sponsors & Collaborators

• Kessler Foundation: lead
• National Institute on Disability, Independent Living, and Rehabilitation Research: collaborator

Study Sites (1)

Kessler Institute for Rehabilitation

West Orange, New Jersey, 07052, United States

RECRUITING

MeSH Terms

Conditions

Spinal Cord Injuries; Urinary Bladder, Neurogenic

Interventions

oxybutynin; mirabegron

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Neurologic Manifestations; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Todd A. Linsenmeyer, M.D.

  Kessler Institute for Rehabilitation

  PRINCIPAL INVESTIGATOR

• Steven C. Kirshblum, M.D.

  Kessler Institute for Rehabilitation

  PRINCIPAL INVESTIGATOR

• Trevor A. Dyson-Hudson, M.D.

  Kessler Foundation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Todd A. Linsenmeyer, M.D.

CONTACT

973-243-6924; tlinsenmeyer@kessler-rehab.com

Trevor A. Dyson-Hudson, M.D.

CONTACT

973-324-3576; tdysonhudson@kesslerfoundation.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All study investigators, participants, and assessors will be blind to group assignment. Blinding code will only be broken in emergency situations for reasons of subject safety, where knowledge of the treatment administered is necessary for the treatment of the adverse event under Good Clinical Practices (GCPs), or when required by local regulatory authorities.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Spinal Cord Injury Research

Model Details: After a two-day washout period, participants will be randomly assigned to one of two treatment groups: 1) an escalating dose of mirabegron for 6 weeks (25 mg once daily plus two placebo pills for 2 weeks, followed by 50 mg once daily plus 2 placebo pills for 4 weeks); or 2) Oxybutynin IR (5 mg orally three times daily) for 6 weeks. All participants will then be switched to the opposite study treatment for 6 weeks. Assessments will be performed at Baseline, Week 6 (completion of first study medication and prior to administration of second study medication), and Week 12 (completion of second study medication).

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: June 15, 2017
• Study Start: April 3, 2019
• Primary Completion: September 30, 2021
• Study Completion: March 30, 2022
• Last Updated: December 17, 2019

Record last verified: 2019-12

Locations

US (1)