<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02981459</url>
  </required_header>
  <id_info>
    <org_study_id>030-586061</org_study_id>
    <nct_id>NCT02981459</nct_id>
  </id_info>
  <brief_title>Mirabegron for the Treatment of Pain Motivated Urinary Frequency and Urgency in Women</brief_title>
  <official_title>Pilot Study: Mirabegron for the Treatment of Pain Motivated Urinary Frequency and Urgency in Women, an Open Label Study With Dose Escalation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>State University of New York at Buffalo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Astellas Pharma Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>State University of New York at Buffalo</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The specific purpose of this study is to provide objective data in prospective open label&#xD;
      design (n=40) to support the use of Mirabegron as a treatment for pain related urinary&#xD;
      frequency and urgency. Women with bladder pain have a poor response to traditional&#xD;
      anticholinergic therapy for their symptoms of frequency and urgency.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypothesis: Mirabegron is effective in reducing symptoms in women with pain related urinary&#xD;
      frequency and urgency.&#xD;
&#xD;
      Specific Aims:&#xD;
&#xD;
        1. To measure the efficacy of Mirabegron in the treatment of frequency and urgency, using&#xD;
           voiding diaries.&#xD;
&#xD;
        2. To measure the number of patients with a 50% or greater reduction in frequency and&#xD;
           urgency, using voiding diaries.&#xD;
&#xD;
        3. To measure the number of patients with a 50% or greater reduction in bladder pain as&#xD;
           measured in the O'Leary-Sant (OLS) IC symptom and problem, and the Lowell Parsons Pelvic&#xD;
           Pain and Urgency/Frequency (PUF) patient symptom scale.&#xD;
&#xD;
      Intervention/Project goal: Treatment with Mirabegron 25mg for 4 weeks with an option for dose&#xD;
      escalation to 50mg. Duration of study 12 weeks.&#xD;
&#xD;
      Inclusion criteria: Women between the ages of 18 and 89 with complaints of pain related&#xD;
      urinary frequency are eligible to participate in the study.&#xD;
&#xD;
      Exclusion criteria:&#xD;
&#xD;
      Patients will be excluded from the study if they have:&#xD;
&#xD;
        1. Severe Liver disease, Child-Pugh class c&#xD;
&#xD;
        2. Severe Kidney disease, GFR&lt;30&#xD;
&#xD;
        3. Elevated blood pressure &gt; 160/95 (in package insert bp &gt;180/110)&#xD;
&#xD;
        4. Urinary retention&#xD;
&#xD;
        5. Pregnant, will become pregnant, or are nursing&#xD;
&#xD;
        6. History of recurrent urinary tract infection&#xD;
&#xD;
        7. Tachycardia: pulse &gt; 100&#xD;
&#xD;
        8. Presently on study drug mirabegron; patient must be willing to participate in a 30 day&#xD;
           washout period to be eligible for inclusion&#xD;
&#xD;
        9. Medications - metoprolol, desipramine, digoxin, propafenone, thioridazine, flecainide,&#xD;
           warfarin&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Withdrawn by Sponsor&#xD;
  </why_stopped>
  <start_date type="Actual">December 8, 2017</start_date>
  <completion_date type="Anticipated">June 2018</completion_date>
  <primary_completion_date type="Anticipated">June 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The number of pain motivated voids per 24 hours.</measure>
    <time_frame>12 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The mean change from baseline to end of study in the daily average number of voids</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Mean change in global urinary symptoms based upon scores from the Urgency Severity and Impact Questionnaire (USIQ)</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The mean change in the Patient Perception of Bladder Condition (PPBC)</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Urinary Frequency/Urgency</condition>
  <condition>Bladder Irritable</condition>
  <condition>Bladder Pain Syndrome</condition>
  <arm_group>
    <arm_group_label>Mirabegron 25 mg or 50 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mirabegron</intervention_name>
    <description>daily mirabegron 25mg with the option to increase dose based on symptoms to 50mg daily after 4 weeks</description>
    <arm_group_label>Mirabegron 25 mg or 50 mg</arm_group_label>
    <other_name>Myrbetriq</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. English-speaking women&#xD;
&#xD;
          2. Age: 18 and 89 years&#xD;
&#xD;
          3. Pain related urinary frequency or urgency associated with &gt;70% of voids. With a&#xD;
             minimum of 7 pain motivated voids in 24 hours.&#xD;
&#xD;
          4. Bladder capacity: &gt; 300 ml&#xD;
&#xD;
          5. Urinary frequency: 10 or more voids in 24/hours on voiding diary&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Severe Liver disease: Child-Pugh class c&#xD;
&#xD;
          2. Severe Kidney disease: GFR&lt;30&#xD;
&#xD;
          3. Elevated blood pressure &gt; 160/95 (in package insert bp &gt;180/110)&#xD;
&#xD;
          4. Pregnant, will become pregnant, or are nursing during the study&#xD;
&#xD;
          5. History of recurrent urinary tract infection: 3 or more culture proven urinary tract&#xD;
             infections in the past 12 months. An active urinary tract infection.&#xD;
&#xD;
          6. Tachycardia: pulse &gt; 100, or any other history of arrhythmia&#xD;
&#xD;
          7. Intense urge: bladder volumes of &lt;150 ml on cystometry&#xD;
&#xD;
          8. Presently on study drug mirabegron; patient must be willing to participate in a 30 day&#xD;
             washout period to be eligible for inclusion&#xD;
&#xD;
          9. Medications: metoprolol, desipramine, digoxin, propafenone, thioridazine, flecainide,&#xD;
             warfarin&#xD;
&#xD;
         10. Pain medications: no dose changes in narcotic or non-steroidal medications while on&#xD;
             study. Patient must be on a stable medication dose for at least 30 days prior to the&#xD;
             screening visit.&#xD;
&#xD;
         11. Neurogenic pain medications such as gabapentin or amitriptyline: no dose changes while&#xD;
             on study. Patient must be on a stable medication dose for at least 30 days prior to&#xD;
             the screening visit.&#xD;
&#xD;
         12. Anticholinergic medications for incontinence: no dose changes while on study. Patient&#xD;
             must be on a stable medication dose for at least 30 days prior to the screening visit.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tova S Ablove, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University at Buffalo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vanessa Barnabei, MD PHD</last_name>
    <role>Study Chair</role>
    <affiliation>University at Buffalo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UBMD Obstetrics and Gynecology</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14222</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>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. doi: 10.1067/mob.2002.125704. No abstract available.</citation>
    <PMID>12114899</PMID>
  </reference>
  <reference>
    <citation>Aizawa N, Homma Y, Igawa Y. Effects of mirabegron, a novel beta3-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.</citation>
    <PMID>22981677</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>19816919</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>23231848</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>23072271</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1016/j.eururo.2006.09.019. Epub 2006 Oct 2.</citation>
    <PMID>17049716</PMID>
  </reference>
  <reference>
    <citation>Michel MC. beta-Adrenergic Receptor Subtypes in the Urinary Tract. Handb Exp Pharmacol. 2011;(202):307-18. doi: 10.1007/978-3-642-16499-6_15.</citation>
    <PMID>21290233</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>21396778</PMID>
  </reference>
  <reference>
    <citation>Milsom I, Abrams P, Cardozo L, Roberts RG, Thuroff 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. doi: 10.1046/j.1464-410x.2001.02228.x. Erratum In: BJU Int 2001 Nov;88(7):807.</citation>
    <PMID>11412210</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1007/s00345-002-0301-4. Epub 2002 Nov 15.</citation>
    <PMID>12811491</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1016/s0090-4295(01)01639-9.</citation>
    <PMID>12007524</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>October 19, 2020</last_update_submitted>
  <last_update_submitted_qc>October 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>State University of New York at Buffalo</investigator_affiliation>
    <investigator_full_name>Tova Ablove</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>bladder pain</keyword>
  <keyword>urinary frequency</keyword>
  <keyword>urinary urgency</keyword>
  <keyword>mirabegron</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystitis, Interstitial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mirabegron</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02981459
org study id: 030-586061
nct id: NCT02981459
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
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
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The number of pain motivated voids per 24 hours.
time frame: 12 weeks
measure: The mean change from baseline to end of study in the daily average number of voids
time frame: 12 weeks
measure: The Mean change in global urinary symptoms based upon scores from the Urgency Severity and Impact Questionnaire (USIQ)
time frame: 12 weeks
measure: The mean change in the Patient Perception of Bladder Condition (PPBC)
time frame: 12 weeks
arm group label: Mirabegron 25 mg or 50 mg
arm group type: Experimental
intervention type: Drug
intervention name: Mirabegron
description: daily mirabegron 25mg with the option to increase dose based on symptoms to 50mg daily after 4 weeks
arm group label: Mirabegron 25 mg or 50 mg
other name: Myrbetriq
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 89 Years
healthy volunteers: No
last name: Tova S Ablove, MD
role: Principal Investigator
affiliation: University at Buffalo
last name: Vanessa Barnabei, MD PHD
role: Study Chair
affiliation: University at Buffalo
facility: 
country: United States
citation: 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. doi: 10.1067/mob.2002.125704. No abstract available.
PMID: 12114899
citation: Aizawa N, Homma Y, Igawa Y. Effects of mirabegron, a novel beta3-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.
PMID: 22981677
citation: 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.
PMID: 19816919
citation: 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.
PMID: 23231848
citation: 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.
PMID: 23072271
citation: 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. doi: 10.1016/j.eururo.2006.09.019. Epub 2006 Oct 2.
PMID: 17049716
citation: Michel MC. beta-Adrenergic Receptor Subtypes in the Urinary Tract. Handb Exp Pharmacol. 2011;(202):307-18. doi: 10.1007/978-3-642-16499-6_15.
PMID: 21290233
citation: 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.
PMID: 21396778
citation: Milsom I, Abrams P, Cardozo L, Roberts RG, Thuroff 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. doi: 10.1046/j.1464-410x.2001.02228.x. Erratum In: BJU Int 2001 Nov;88(7):807.
PMID: 11412210
citation: 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. doi: 10.1007/s00345-002-0301-4. Epub 2002 Nov 15.
PMID: 12811491
citation: 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. doi: 10.1016/s0090-4295(01)01639-9.
PMID: 12007524
responsible party type: Principal Investigator
investigator affiliation: State University of New York at Buffalo
investigator full name: Tova Ablove
investigator title: Principal Investigator
mesh term: Cystitis, Interstitial
mesh term: Mirabegron
sharing ipd: No