Open Label Transdermal Granisetron to Relieve Chronic Nausea and Emesis

Open Label Transdermal Granisetron to Relieve Chronic Nausea and Emesis and to Reduce Medical Utilization in Patients With Gastroparesis

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

Study Overview

• Status: Withdrawn
• Conditions: Gastroparesis
• Intervention / Treatment: Drug: Granisetron

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

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patch arm; 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	Drug: Granisetron; transdermal sancuso patch; Other Names: sancuso patch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 weeks

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: Kyowa Kirin, Inc.
• Investigators: Principal Investigator: John M Wo, MD, Indiana University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2019
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: August 1, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Actual): February 14, 2022
• Last Update Submitted That Met QC Criteria: February 11, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neurologic Manifestations; Gastrointestinal Diseases; Stomach Diseases; Paralysis; Gastroparesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Serotonin Agents; Serotonin Antagonists; Granisetron
• Other Study ID Numbers: 1706966663

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No