Domperidone in Treating Patients With Gastrointestinal Disorders

Study Overview
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Brief Summary
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This phase III trial studies how well domperidone works in treating patients with gastrointestinal disorders. Domperidone may help control chronic gastrointestinal disorders and their symptoms, such as pain, bloating, and nausea and vomiting, by stimulating contraction of the stomach to increase its ability to empty itself of food.

Detailed Description
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PRIMARY OBJECTIVES: I. To provide treatment with domperidone to patients >= 16 years of age where, according to the investigators' judgment, a prokinetic effect is needed for the relief of gastrointestinal (GI) motility disorders. OUTLINE: Patients receive domperidone orally (PO) thrice daily (TID) or four times daily (QID). Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for at least 30 days.

Official Title
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Treatment Protocol for the Compassionate Use of Domperidone

Conditions
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Digestive System Disorder, Dyspepsia, Esophagitis, Gastroesophageal Reflux Disease, Gastroparesis, Heartburn, Nausea and Vomiting

Intervention / Treatment
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* Drug: Domperidone
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with GI disorders who have failed standard therapy Symptoms or manifestations of: a) gastroparesis; b) refractory gastroesophageal reflux disease (GERD) including persistent esophagitis, refractory heartburn, reflux-related laryngitis, and respiratory symptoms; or c) severe dyspepsia Completion of a comprehensive evaluation, including clinical history and physical examination, to eliminate other causes of their symptoms Patient has signed the informed consent document agreeing to the use of the study drug, domperidone White blood cell (WBC) with differential greater than 3,000/ml Alkaline phosphatase less than 1.5 x upper limit of normal Alanine aminotransferase (ALT) less than 2 x upper limit of normal Aspartate aminotransferase (AST) less than 2 x upper limit of normal Bilirubin less than or equal to 2 x upper limit of normal Blood urea nitrogen (BUN) less than 2 x upper limit of normal Creatinine less than 1.5 x upper limit of normal Stable hemoglobin greater than or equal to 8.0 g/dl Potassium between range of 3.0 to 5.5 Magnesium level between 1.6-2.6 mg Exclusion Criteria: Patients with the following cardiac diagnoses: ventricular tachycardia or fibrillation; Torsade des Pointes; clinically significant bradycardia; sinus node dysfunction; heart block; prolonged QTc interval (QTc > 450 milliseconds for males, QTc > 470 milliseconds for females); prior specific cardiovascular conditions of clinically significant valvular heart disease requiring medication, ischemic, or pulmonary heart disease; cardiomyopathy; history of heart failure Patients who are receiving antiarrhythmic medications with action on repolarization times (with prolongation of the QTc interval such as amiodarone, disopyramide, dofetilide, flecainide, ibutilide, quinidine, sotalol, dronedarone etc.) Patients who are receiving monoamine oxidase (MAO) inhibitors Patients with a history of or active liver failure Clinically significant electrolyte disorders including sodium < 130 or > 145 and/or potassium < 3.0 or > 5.5 and/or magnesium < 1.6 or > 2.6 GI hemorrhage or obstruction experienced within the previous 6 weeks Presence of a prolactinoma (prolactin-releasing pituitary tumor) Pregnant or breast-feeding female (women of childbearing potential [WOCBP], defined as not post-menopausal for 12 months or without previous surgical sterilization, must have a negative urine pregnancy test within 30 days of the first administration of domperidone and must either commit to continued abstinence from heterosexual intercourse or use an effective method of birth control during the course of the study) Known allergy to domperidone

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (domperidone)<br>Patients receive domperidone PO TID or QID. Treatment continues in the absence of disease progression or unacceptable toxicity. | Drug: Domperidone<br>* Given PO<br>* Other names: R 33,812;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attenuation of symptoms associated with disorder(s) of gastrointestinal motility, measured by change in Gastroparesis Cardinal Symptom Index (GSCI) score from baseline | Scale ranges from 0 meaning None to 5 meaning Very Severe. Patients will be classified as either new or continuing at the baseline visit. A new patient will have a response if he/she has a 25% reduction in GCSI at 8 weeks. A continuing patient will already have early benefit to treatment so will have a response if the GCSI score does not increase more than 20% over baseline at 8 weeks. Summary statistics including number (n), mean, standard deviation, median, minimum, and maximum will be computed. Bayesian 95% credible intervals will be computed. | Baseline to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in patients' self-report of symptoms | Summary statistics including n, mean, standard deviation, median, minimum, and maximum will be computed. Bayesian 95% credible intervals will be computed. | Baseline to 30 days after completion of study treatment | 
| Incidence of toxicities assessed according to the Common Terminology Criteria for Adverse Events version 4.0 | Summary statistics including n, mean, standard deviation, median, minimum, and maximum will be computed. Bayesian 95% credible intervals will be computed. Patient adverse events will be tabulated by symptom, grade, and relationship to study drug. | Up to 30 days after completion of study treatment |