Pharmacokinetics of Immediate-Release vs. Delayed-Release Omeprazole in Gastroparesis

Study Overview
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Brief Summary
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The purpose of this study is to compare the blood drug levels of two prescribed medications, immediate-release omeprazole 40 mg powder and delayed-release omeprazole 40 mg capsule to determine which drug is better absorbed in patients with a slow stomach emptying (gastroparesis). Delayed-release omeprazole has a protective coating to prevent the drug omeprazole from being neutralized by stomach acid. Immediate-release omeprazole has sodium bicarbonate (antacid) which neutralizes the stomach acid, eliminating the need for a protective coating. Immediate-release omeprazole suspension may have a more rapid pharmacokinetic profile and greater overall drug absorption in gastroparesis.

Detailed Description
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Hypothesis: Immediate-release omeprazole suspension may have a more rapid pharmacokinetic profile and greater overall drug absorption in gastroparesis. This will result in shorter time to maximal drug concentration, greater maximal concentration, and greater total area under the curve of the concentration vs. time plot. Primary Objective: To compare the pharmacokinetics of omeprazole between immediate-release suspension and delayed-release capsules in patients with heartburn associated with gastroparesis. Study design: randomized, open-labeled, crossover treatment for 7 days with 10-14 days washout. Pharmacokinetic studies will be performed after 7 days on study drug.

Official Title
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Pharmacokinetics of Immediate-Release vs. Delayed-Release Omeprazole in Patients With Heartburn Associated With Gastroparesis

Conditions
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Gastroparesis, Gastroesophageal Reflux Disease

Intervention / Treatment
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* Drug: Immediate-release omeprazole
* Drug: Delayed-release omeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms of heartburn >2 days per week off antireflux therapy, defined by a burning feeling rising from the stomach or lower chest up towards the neck Symptoms of gastroparesis >1 month in duration, defined by nausea, vomiting, bloating, dyspepsia, early satiety, or effortless regurgitation. Prior abnormal 4-hour gastric emptying scan within the past 3 years Exclusion Criteria: History of esophageal or gastric surgery Severe gastroparesis with any of the following: vomiting with dehydration requiring IV hydration, hospitalization, weight loss >10 % pre-illness weight, requiring feeding jejunostomy tubes Presence of gastric electrical stimulator Symptoms of retching with vomiting more than 2 days per week Diagnosis of diabetes Disorders of small bowel motility (such as pseudo-obstruction or dumping syndrome) Disorders of small bowel absorption Diagnosis of gastric outlet, small bowel or colon mechanical obstruction Diagnosis of acid hypersecretory syndrome Disorders affecting proton pump inhibitor metabolism (such as liver failure) Known allergy or side effects to proton pump inhibitor Non-ambulatory patients: bed-ridden, nursing home resident, etc. Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate-release omeprazole release first<br>subjects receive immediate release omeprazole for 7 days then delayed release for 7 days | Drug: Immediate-release omeprazole<br>* Immediate-release omeprazole 40 mg qam for 7 days<br>Drug: Delayed-release omeprazole<br>* Delayed-release omeprazole 40 mg qam for 7 days<br>|
| Experimental: Delayed-release omeprazole first<br>subjects receive delayed release omeprazole for 7 days then immediate release for 7 days | Drug: Immediate-release omeprazole<br>* Immediate-release omeprazole 40 mg qam for 7 days<br>Drug: Delayed-release omeprazole<br>* Delayed-release omeprazole 40 mg qam for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Maximal Omeprazole Concentration (Tmax) | Time to max concentration for Immediate release vs. Delayed release omeprazole | 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 and 300 min after the study drug was ingested on day 7 of treatment | 
| Maximal Concentration of Omerazole | Maximal concentration of immediate-release vs. delayed-release omeprazole | 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 and 300 min after the study drug was ingested on day 7 of treatment | 
| Area Under the Curve for Omeprazole Plasma Concentration | The area under the curve for omeprazole concentration-time curve for immediate release and delayed release omeprazole. | 0 to 5 hrs after the study drug was ingested on treatment day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastroparesis, Gastroesophageal reflux disease, heartburn