Open Label Transdermal Granisetron to Relieve Chronic Nausea and Emesis

Indiana University

Status and phase

Withdrawn

Phase 2

Conditions

Gastroparesis

Treatments

Drug: Granisetron

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04501211

1706966663

Details and patient eligibility

About

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

Full 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

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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
2. CYP1A1 Inhibitors: pifithrin, ethinyl estradiol, fluvoxamine (Luvox®), mexiletine, miconazole, oltipraz , perazine, rofecoxib, aminobenzotriazole, isoniazid, lidocaine, zileuton (Zyflo®)
3. 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