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Open Label Transdermal Granisetron to Relieve Chronic Nausea and Emesis

Primary Purpose

Gastroparesis

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Granisetron
Sponsored by
Indiana University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastroparesis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Documented delayed gastric emptying by 4-hr gastric scintigraphy using the standard protocol within 12 months.6
  2. Symptoms of gastroparesis for >3 months
  3. No upper gastrointestinal obstruction by upper endoscopy, barium radiograph, or CT scan.
  4. Gastroparesis Cardinal Symptom Index Nausea-Vomiting (GCSI-N/V) subscale score of >2.0 during a 2-week run-in period.

Exclusion Criteria:

  • 1. Baseline ECG with QTc >450ms in men or >470ms in women 2. Prolong QT syndrome 3. History of Torsade's de pointes, ventricular tachycardia, cardiomyopathy or implanted cardiac defibrillator 4. Use of cardiovascular antiarrhythmic medications 5. Strong CYP1A1 and CYP3A4 inhibitors that will inhibit metabolism of 5-HT3 antagonists

    1. CYP1A1 Inhibitors: pifithrin, ethinyl estradiol, fluvoxamine (Luvox®), mexiletine, miconazole, oltipraz , perazine, rofecoxib, aminobenzotriazole, isoniazid, lidocaine, zileuton (Zyflo®)
    2. CYP3A strong inhibitors: boceprevir, cobicistat (Tybost®), conivaptan (Vaprisol®), danoprevir and ritonavir, elvitegravir and ritonavir, grapefruit juice, indinavir and ritonavir, itraconazole (Onmel®, Sporanox®), ketoconazole, lopinavir and ritonavir (Kaletra®), paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), posaconazole (Noxafil®), ritonavir (Norvir®), saquinavir and ritonavir), tipranavir and ritonavir, troleandomycin, voriconazole (Vfend®), clarithromycin (Biaxin®), diltiazem (Cardizem®, Cartia®, Dilacor®, Dilt-CD®, Diltia XT®, Taztia XT®, Tiazac®), idelalisib (Zydelig®), nefazodone (Serzone®), nelfinavir (Viracept®) 6. Serotonergic drugs that may increase the risk of serotonin syndrome
    1. Selective serotonin reuptake inhibitors (SSRIs)
    2. Selective norepinephrine reuptake inhibitors (SNRIs)
    3. Others: monoamine oxidase inhibitors: selegiline (Emsam®), isocarboxazid (Marplan®), pheneizine (Nardil®), tranylcypromine (Parnate®), mirtazapine (Remeron®), fentanyl (Sublimaze®), lithium (Eskalith®, Lithobid®), tramadol (ConZip®, Rybix®, Ryzolt®, Ultram®), intravenous methylene blue 7. Any comorbid condition that may prohibit enrollment 8. Other causes of nausea identified by the investigators other than gastroparesis 9. Any contraindications for 5HT3 receptor antagonists 10. Non-ambulatory patients: bed-ridden, nursing home resident, etc. 11. Pregnancy 12. Unable to give own informed consent 13. Prisoners

Sites / Locations

  • Indiana University

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Patch arm

Arm 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

Outcomes

Primary Outcome Measures

Number of participants with improvement in chronic nausea and emesis.
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.

Secondary Outcome Measures

Number of participants with reduced medical utilization for gastroparesis.
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.

Full Information

First Posted
October 31, 2018
Last Updated
February 11, 2022
Sponsor
Indiana University
Collaborators
Kyowa Kirin, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04501211
Brief Title
Open Label Transdermal Granisetron to Relieve Chronic Nausea and Emesis
Official Title
Open Label Transdermal Granisetron to Relieve Chronic Nausea and Emesis and to Reduce Medical Utilization in Patients With Gastroparesis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Abandoned due to limited resources
Study Start Date
January 1, 2019 (Anticipated)
Primary Completion Date
December 31, 2020 (Anticipated)
Study Completion Date
December 31, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indiana University
Collaborators
Kyowa Kirin, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To determine the efficacy of open -label transdermal patch on chronic nausea and emesis in patients with gastroparesis
Detailed Description
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastroparesis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Patch arm
Arm Type
Other
Arm 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(s)
Granisetron
Other Intervention Name(s)
sancuso patch
Intervention Description
transdermal sancuso patch
Primary Outcome Measure Information:
Title
Number of participants with improvement in chronic nausea and emesis.
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.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Number of participants with reduced medical utilization for gastroparesis.
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.
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Documented delayed gastric emptying by 4-hr gastric scintigraphy using the standard protocol within 12 months.6 Symptoms of gastroparesis for >3 months No upper gastrointestinal obstruction by upper endoscopy, barium radiograph, or CT scan. Gastroparesis Cardinal Symptom Index Nausea-Vomiting (GCSI-N/V) subscale score of >2.0 during a 2-week run-in period. Exclusion Criteria: 1. Baseline ECG with QTc >450ms in men or >470ms in women 2. Prolong QT syndrome 3. History of Torsade's de pointes, ventricular tachycardia, cardiomyopathy or implanted cardiac defibrillator 4. Use of cardiovascular antiarrhythmic medications 5. Strong CYP1A1 and CYP3A4 inhibitors that will inhibit metabolism of 5-HT3 antagonists CYP1A1 Inhibitors: pifithrin, ethinyl estradiol, fluvoxamine (Luvox®), mexiletine, miconazole, oltipraz , perazine, rofecoxib, aminobenzotriazole, isoniazid, lidocaine, zileuton (Zyflo®) CYP3A strong inhibitors: boceprevir, cobicistat (Tybost®), conivaptan (Vaprisol®), danoprevir and ritonavir, elvitegravir and ritonavir, grapefruit juice, indinavir and ritonavir, itraconazole (Onmel®, Sporanox®), ketoconazole, lopinavir and ritonavir (Kaletra®), paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), posaconazole (Noxafil®), ritonavir (Norvir®), saquinavir and ritonavir), tipranavir and ritonavir, troleandomycin, voriconazole (Vfend®), clarithromycin (Biaxin®), diltiazem (Cardizem®, Cartia®, Dilacor®, Dilt-CD®, Diltia XT®, Taztia XT®, Tiazac®), idelalisib (Zydelig®), nefazodone (Serzone®), nelfinavir (Viracept®) 6. Serotonergic drugs that may increase the risk of serotonin syndrome Selective serotonin reuptake inhibitors (SSRIs) Selective norepinephrine reuptake inhibitors (SNRIs) Others: monoamine oxidase inhibitors: selegiline (Emsam®), isocarboxazid (Marplan®), pheneizine (Nardil®), tranylcypromine (Parnate®), mirtazapine (Remeron®), fentanyl (Sublimaze®), lithium (Eskalith®, Lithobid®), tramadol (ConZip®, Rybix®, Ryzolt®, Ultram®), intravenous methylene blue 7. Any comorbid condition that may prohibit enrollment 8. Other causes of nausea identified by the investigators other than gastroparesis 9. Any contraindications for 5HT3 receptor antagonists 10. Non-ambulatory patients: bed-ridden, nursing home resident, etc. 11. Pregnancy 12. Unable to give own informed consent 13. Prisoners
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John M Wo, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Open Label Transdermal Granisetron to Relieve Chronic Nausea and Emesis

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