Mirabegron for the Treatment of Pain Motivated Urinary Frequency and Urgency in Women

Overview

The specific purpose of this study is to provide objective data in prospective open label design (n=40) to support the use of Mirabegron as a treatment for pain related urinary frequency and urgency. Women with bladder pain have a poor response to traditional anticholinergic therapy for their symptoms of frequency and urgency.

Full Title of Study: “Pilot Study: Mirabegron for the Treatment of Pain Motivated Urinary Frequency and Urgency in Women, an Open Label Study With Dose Escalation”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 2018

Detailed Description

Hypothesis: Mirabegron is effective in reducing symptoms in women with pain related urinary frequency and urgency. Specific Aims: 1. To measure the efficacy of Mirabegron in the treatment of frequency and urgency, using voiding diaries. 2. To measure the number of patients with a 50% or greater reduction in frequency and urgency, using voiding diaries. 3. To measure the number of patients with a 50% or greater reduction in bladder pain as measured in the O'Leary-Sant (OLS) IC symptom and problem, and the Lowell Parsons Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. Intervention/Project goal: Treatment with Mirabegron 25mg for 4 weeks with an option for dose escalation to 50mg. Duration of study 12 weeks. Inclusion criteria: Women between the ages of 18 and 89 with complaints of pain related urinary frequency are eligible to participate in the study. Exclusion criteria: Patients will be excluded from the study if they have: 1. Severe Liver disease, Child-Pugh class c 2. Severe Kidney disease, GFR<30 3. Elevated blood pressure > 160/95 (in package insert bp >180/110) 4. Urinary retention 5. Pregnant, will become pregnant, or are nursing 6. History of recurrent urinary tract infection 7. Tachycardia: pulse > 100 8. Presently on study drug mirabegron; patient must be willing to participate in a 30 day washout period to be eligible for inclusion 9. Medications – metoprolol, desipramine, digoxin, propafenone, thioridazine, flecainide, warfarin

Interventions

  • Drug: Mirabegron
    • daily mirabegron 25mg with the option to increase dose based on symptoms to 50mg daily after 4 weeks

Arms, Groups and Cohorts

  • Experimental: Mirabegron 25 mg or 50 mg

Clinical Trial Outcome Measures

Primary Measures

  • The number of pain motivated voids per 24 hours.
    • Time Frame: 12 weeks

Secondary Measures

  • The mean change from baseline to end of study in the daily average number of voids
    • Time Frame: 12 weeks
  • The Mean change in global urinary symptoms based upon scores from the Urgency Severity and Impact Questionnaire (USIQ)
    • Time Frame: 12 weeks
  • The mean change in the Patient Perception of Bladder Condition (PPBC)
    • Time Frame: 12 weeks

Participating in This Clinical Trial

Inclusion Criteria

1. English-speaking women 2. Age: 18 and 89 years 3. Pain related urinary frequency or urgency associated with >70% of voids. With a minimum of 7 pain motivated voids in 24 hours. 4. Bladder capacity: > 300 ml 5. Urinary frequency: 10 or more voids in 24/hours on voiding diary Exclusion Criteria:

1. Severe Liver disease: Child-Pugh class c 2. Severe Kidney disease: GFR<30 3. Elevated blood pressure > 160/95 (in package insert bp >180/110) 4. Pregnant, will become pregnant, or are nursing during the study 5. History of recurrent urinary tract infection: 3 or more culture proven urinary tract infections in the past 12 months. An active urinary tract infection. 6. Tachycardia: pulse > 100, or any other history of arrhythmia 7. Intense urge: bladder volumes of <150 ml on cystometry 8. Presently on study drug mirabegron; patient must be willing to participate in a 30 day washout period to be eligible for inclusion 9. Medications: metoprolol, desipramine, digoxin, propafenone, thioridazine, flecainide, warfarin 10. Pain medications: no dose changes in narcotic or non-steroidal medications while on study. Patient must be on a stable medication dose for at least 30 days prior to the screening visit. 11. Neurogenic pain medications such as gabapentin or amitriptyline: no dose changes while on study. Patient must be on a stable medication dose for at least 30 days prior to the screening visit. 12. Anticholinergic medications for incontinence: no dose changes while on study. Patient must be on a stable medication dose for at least 30 days prior to the screening visit.

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 89 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • State University of New York at Buffalo
  • Collaborator
    • Astellas Pharma Inc
  • Provider of Information About this Clinical Study
    • Principal Investigator: Tova Ablove, Principal Investigator – State University of New York at Buffalo
  • Overall Official(s)
    • Tova S Ablove, MD, Principal Investigator, University at Buffalo
    • Vanessa Barnabei, MD PHD, Study Chair, University at Buffalo

References

Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, van Kerrebroeck P, Victor A, Wein A. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Am J Obstet Gynecol. 2002 Jul;187(1):116-26.

Aizawa N, Homma Y, Igawa Y. Effects of mirabegron, a novel β3-adrenoceptor agonist, on primary bladder afferent activity and bladder microcontractions in rats compared with the effects of oxybutynin. Eur Urol. 2012 Dec;62(6):1165-73. doi: 10.1016/j.eururo.2012.08.056. Epub 2012 Sep 5.

Aizawa N, Igawa Y, Nishizawa O, Wyndaele JJ. Effects of CL316,243, a beta 3-adrenoceptor agonist, and intravesical prostaglandin E2 on the primary bladder afferent activity of the rat. Neurourol Urodyn. 2010 Jun;29(5):771-6. doi: 10.1002/nau.20826.

Geoffrion R; UROGYNAECOLOGY COMMITTEE. Treatments for overactive bladder: focus on pharmacotherapy. J Obstet Gynaecol Can. 2012 Nov;34(11):1092-1101. doi: 10.1016/S1701-2163(16)35440-8.

Hood B, Andersson KE. Common theme for drugs effective in overactive bladder treatment: inhibition of afferent signaling from the bladder. Int J Urol. 2013 Jan;20(1):21-7. doi: 10.1111/j.1442-2042.2012.03196.x. Epub 2012 Oct 17. Review.

Irwin DE, Milsom I, Hunskaar S, Reilly K, Kopp Z, Herschorn S, Coyne K, Kelleher C, Hampel C, Artibani W, Abrams P. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006 Dec;50(6):1306-14; discussion 1314-5. Epub 2006 Oct 2.

Michel MC. β-Adrenergic Receptor Subtypes in the Urinary Tract. Handb Exp Pharmacol. 2011;(202):307-18. doi: 10.1007/978-3-642-16499-6_15. Review.

Miki T, Matsunami M, Nakamura S, Okada H, Matsuya H, Kawabata A. ONO-8130, a selective prostanoid EP1 receptor antagonist, relieves bladder pain in mice with cyclophosphamide-induced cystitis. Pain. 2011 Jun;152(6):1373-1381. doi: 10.1016/j.pain.2011.02.019. Epub 2011 Mar 10.

Milsom I, Abrams P, Cardozo L, Roberts RG, Thüroff J, Wein AJ. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int. 2001 Jun;87(9):760-6. Erratum in: BJU Int 2001 Nov;88(7):807.

Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, Hunt TL, Wein AJ. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003 May;20(6):327-36. Epub 2002 Nov 15.

Yoshimura N, Seki S, Chancellor MB, de Groat WC, Ueda T. Targeting afferent hyperexcitability for therapy of the painful bladder syndrome. Urology. 2002 May;59(5 Suppl 1):61-7.

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