<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/NCT04501211</url>
  </required_header>
  <id_info>
    <org_study_id>1706966663</org_study_id>
    <nct_id>NCT04501211</nct_id>
  </id_info>
  <brief_title>Open Label Transdermal Granisetron to Relieve Chronic Nausea and Emesis</brief_title>
  <official_title>Open Label Transdermal Granisetron to Relieve Chronic Nausea and Emesis and to Reduce Medical Utilization in Patients With Gastroparesis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kyowa Kirin, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Indiana University</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>
      To determine the efficacy of open -label transdermal patch on chronic nausea and emesis in&#xD;
      patients with gastroparesis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Gastroparesis is a chronic syndrome associated with a delay in stomach emptying. The clinical&#xD;
      presentation of gastroparesis is very heterogeneous but can generally categorized into&#xD;
      emesis-predominant, regurgitation-predominant and dyspeptic-predominant gastroparesis.&#xD;
&#xD;
      The underlying cause of nausea is very difficult to identify, and physician is often treat&#xD;
      nausea symptomatically with anti-nausea and anti-emetic medications.4, 5 Phenothiazine's such&#xD;
      as prochlorperazine (Compazine®), promethazine (Phenergan®), and trimethobenzamide (Tigan®)&#xD;
      have significant side effects and the potential of withdraw symptoms when these medications&#xD;
      are stopped. Serotonin (5- HT3) antagonists have central emetic effects and have been&#xD;
      utilized in acute chemotherapy-induced nausea and vomiting. Ondansetron, granisetron,&#xD;
      palonosetron, and dolasetron are currently available as 5- HT3 antagonists for nausea and&#xD;
      emesis. Oral dissolving and oral tablet formulation is suboptimal in outpatients with&#xD;
      frequent emesis. Transdermal formulation may be optimal for patients with prolong nausea and&#xD;
      vomiting, but data for chronic symptoms associated with gastroparesis is very limited.&#xD;
&#xD;
      An open-label, uncontrolled treatment pilot study with 2-week cycles of granisetron&#xD;
      transdermal patch for 24 weeks in patients with chronic nausea and vomiting associated with&#xD;
      gastroparesis&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Abandoned due to limited resources&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <phase>Phase 2</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>Number of participants with improvement in chronic nausea and emesis.</measure>
    <time_frame>24 weeks</time_frame>
    <description>Incidence of participants who benefitted from the use of the patch at the end of 2 weeks, 8 weeks, 16 weeks and 24 weeks as assessed by the Gastroparesis Cardinal Symptom Index Nausea-Vomiting (GCSI-N/V). Mean subscale scores will compared for improvement every 6 weeks.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with reduced medical utilization for gastroparesis.</measure>
    <time_frame>24 weeks</time_frame>
    <description>Incidence of participants who required less medical resources during treatment by comparing subject self-reports of medication usage, ER visits, home health therapy, and hospitalizations 12 weeks before, 12 weeks after, and 24 weeks after treatment with open label transdermal granisetron.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Gastroparesis</condition>
  <arm_group>
    <arm_group_label>Patch arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Transdermal Granisetron patch to be given for application for 24 weeks with 2 weeks on and one week off pattern for a total of 24 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Granisetron</intervention_name>
    <description>transdermal sancuso patch</description>
    <arm_group_label>Patch arm</arm_group_label>
    <other_name>sancuso patch</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Documented delayed gastric emptying by 4-hr gastric scintigraphy using the standard&#xD;
             protocol within 12 months.6&#xD;
&#xD;
          2. Symptoms of gastroparesis for &gt;3 months&#xD;
&#xD;
          3. No upper gastrointestinal obstruction by upper endoscopy, barium radiograph, or CT&#xD;
             scan.&#xD;
&#xD;
          4. Gastroparesis Cardinal Symptom Index Nausea-Vomiting (GCSI-N/V) subscale score of &gt;2.0&#xD;
             during a 2-week run-in period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Baseline ECG with QTc &gt;450ms in men or &gt;470ms in women 2. Prolong QT syndrome 3.&#xD;
             History of Torsade's de pointes, ventricular tachycardia, cardiomyopathy or implanted&#xD;
             cardiac defibrillator 4. Use of cardiovascular antiarrhythmic medications 5. Strong&#xD;
             CYP1A1 and CYP3A4 inhibitors that will inhibit metabolism of 5-HT3 antagonists&#xD;
&#xD;
               1. CYP1A1 Inhibitors: pifithrin, ethinyl estradiol, fluvoxamine (Luvox®),&#xD;
                  mexiletine, miconazole, oltipraz , perazine, rofecoxib, aminobenzotriazole,&#xD;
                  isoniazid, lidocaine, zileuton (Zyflo®)&#xD;
&#xD;
               2. CYP3A strong inhibitors: boceprevir, cobicistat (Tybost®), conivaptan&#xD;
                  (Vaprisol®), danoprevir and ritonavir, elvitegravir and ritonavir, grapefruit&#xD;
                  juice, indinavir and ritonavir, itraconazole (Onmel®, Sporanox®), ketoconazole,&#xD;
                  lopinavir and ritonavir (Kaletra®), paritaprevir and ritonavir and (ombitasvir&#xD;
                  and/or dasabuvir), posaconazole (Noxafil®), ritonavir (Norvir®), saquinavir and&#xD;
                  ritonavir), tipranavir and ritonavir, troleandomycin, voriconazole (Vfend®),&#xD;
                  clarithromycin (Biaxin®), diltiazem (Cardizem®, Cartia®, Dilacor®, Dilt-CD®,&#xD;
                  Diltia XT®, Taztia XT®, Tiazac®), idelalisib (Zydelig®), nefazodone (Serzone®),&#xD;
                  nelfinavir (Viracept®) 6. Serotonergic drugs that may increase the risk of&#xD;
                  serotonin syndrome&#xD;
&#xD;
               1. Selective serotonin reuptake inhibitors (SSRIs)&#xD;
&#xD;
               2. Selective norepinephrine reuptake inhibitors (SNRIs)&#xD;
&#xD;
               3. Others: monoamine oxidase inhibitors: selegiline (Emsam®), isocarboxazid&#xD;
                  (Marplan®), pheneizine (Nardil®), tranylcypromine (Parnate®), mirtazapine&#xD;
                  (Remeron®), fentanyl (Sublimaze®), lithium (Eskalith®, Lithobid®), tramadol&#xD;
                  (ConZip®, Rybix®, Ryzolt®, Ultram®), intravenous methylene blue 7. Any comorbid&#xD;
                  condition that may prohibit enrollment 8. Other causes of nausea identified by&#xD;
                  the investigators other than gastroparesis 9. Any contraindications for 5HT3&#xD;
                  receptor antagonists 10. Non-ambulatory patients: bed-ridden, nursing home&#xD;
                  resident, etc. 11. Pregnancy 12. Unable to give own informed consent 13.&#xD;
                  Prisoners&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John M Wo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Indiana University</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>October 31, 2018</study_first_submitted>
  <study_first_submitted_qc>August 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>February 11, 2022</last_update_submitted>
  <last_update_submitted_qc>February 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>John M. Wo</investigator_full_name>
    <investigator_title>Professor of Gastroenterology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastroparesis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Granisetron</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/NCT04501211
org study id: 1706966663
nct id: NCT04501211
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
To determine the efficacy of open -label transdermal patch on chronic nausea and emesis in
      patients with gastroparesis
Gastroparesis is a chronic syndrome associated with a delay in stomach emptying. The clinical
      presentation of gastroparesis is very heterogeneous but can generally categorized into
      emesis-predominant, regurgitation-predominant and dyspeptic-predominant gastroparesis.

      The underlying cause of nausea is very difficult to identify, and physician is often treat
      nausea symptomatically with anti-nausea and anti-emetic medications.4, 5 Phenothiazine's such
      as prochlorperazine (Compazine®), promethazine (Phenergan®), and trimethobenzamide (Tigan®)
      have significant side effects and the potential of withdraw symptoms when these medications
      are stopped. Serotonin (5- HT3) antagonists have central emetic effects and have been
      utilized in acute chemotherapy-induced nausea and vomiting. Ondansetron, granisetron,
      palonosetron, and dolasetron are currently available as 5- HT3 antagonists for nausea and
      emesis. Oral dissolving and oral tablet formulation is suboptimal in outpatients with
      frequent emesis. Transdermal formulation may be optimal for patients with prolong nausea and
      vomiting, but data for chronic symptoms associated with gastroparesis is very limited.

      An open-label, uncontrolled treatment pilot study with 2-week cycles of granisetron
      transdermal patch for 24 weeks in patients with chronic nausea and vomiting associated with
      gastroparesis
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with improvement in chronic nausea and emesis.
time frame: 24 weeks
description: Incidence of participants who benefitted from the use of the patch at the end of 2 weeks, 8 weeks, 16 weeks and 24 weeks as assessed by the Gastroparesis Cardinal Symptom Index Nausea-Vomiting (GCSI-N/V). Mean subscale scores will compared for improvement every 6 weeks.
measure: Number of participants with reduced medical utilization for gastroparesis.
time frame: 24 weeks
description: Incidence of participants who required less medical resources during treatment by comparing subject self-reports of medication usage, ER visits, home health therapy, and hospitalizations 12 weeks before, 12 weeks after, and 24 weeks after treatment with open label transdermal granisetron.
arm group label: Patch arm
arm group type: Other
description: Transdermal Granisetron patch to be given for application for 24 weeks with 2 weeks on and one week off pattern for a total of 24 weeks
intervention type: Drug
intervention name: Granisetron
description: transdermal sancuso patch
arm group label: Patch arm
other name: sancuso patch
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: John M Wo, MD
role: Principal Investigator
affiliation: Indiana University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Indiana University
investigator full name: John M. Wo
investigator title: Professor of Gastroenterology
mesh term: Gastroparesis
mesh term: Granisetron
sharing ipd: No