A Study to Estimate Effect of 4 Different Doses of AZD3355 on Reflux Episodes, Which Patients With Gastroesophageal Reflux Disease (GERD) May Experience

Study Overview
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Brief Summary
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The purpose of the study is to estimate what effect 4 different doses of AZD3355 will have on the number of reflux episodes, in patients who have GERD and still experience symptoms despite proton pump inhibitor (PPI) treatment.

Official Title
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A Double-blind, Placebo Controlled, Randomised, Phase IIA Pharmacodynamic 4-way Cross-over Study to Estimate the Dose Response Relationship of AZD3355 on the Number of Reflux Episodes Assessed by Impedance/pH in Patients With GERD and a Partial Response to PPI Treatment

Conditions
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Gastroesophageal Reflux Disease

Intervention / Treatment
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* Drug: AZD3355
* Drug: AZD3355
* Drug: AZD3355
* Drug: AZD3355
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide informed consent History of GERD with persistent symptoms despite treatment with PPI Otherwise normal physical health Exclusion Criteria: History of GERD with symptoms that has not improved at all during treatment with PPI Prior surgery of the upper gastrointestinal tract History of significant heart disease, cardiovascular, respiratory, hepatic, renal, metabolic, psychiatric or gastrointestinal disorders besides GERD

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>AZD3355 30 mg | Drug: AZD3355<br>* 30 mg orally in the morning and 30 mg in the evening for 1 day<br>|
| Experimental: B<br>AZD3355 90 mg | Drug: AZD3355<br>* 90 mg orally in the morning and 90 mg in the evening for 1 day<br>|
| Experimental: C<br>AZD3355 120 mg | Drug: AZD3355<br>* 120 mg orally in the morning and 120 mg in the evening for 1 day<br>|
| Experimental: D<br>AZD3355 240 mg | Drug: AZD3355<br>* 240 mg orally in the morning and 240 mg in the evening for 1 day<br>|
| Placebo Comparator: E<br>Placebo | Drug: placebo<br>* Placebo capsules orally in the morning and placebo capsules in the evening for 1 day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Reflux Episodes During 24 Hours | Number of reflux episodes assessed during ambulatory impedance-pH recording (defined as starting with a drop in impedance to below 50% of baseline and ending when impedance recovers to above 50% of baseline) | Measured during 24 hours at 4 different visits with a 7-28 days interval between | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Acid Reflux Episodes | Number of reflux episodes as defined for the primary outcome measure with an intraesophageal pH <4 (or a drop of at least 1 pH unit if pH is already <4) lasting more than 5 s. | Measured during 24 hours at 4 different visits with a 7-28 days interval between | 
| Number of Weakly Acidic Reflux Episodes | Number of reflux episodes as defined for the primary outcome measure with an intraesophageal pH 4.0-6.5 lasting more than 5 s. | Measured during 24 hours at 4 different visits with a 7-28 days interval between | 
| Number of Weakly Alkaline Reflux Episodes | Number of reflux episodes as defined for the primary outcome measure with an intraesophageal pH ≥6.5 lasting more than 5 s. | Measured during 24 hours at 4 different visits with a 7-28 days interval between | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pH, GERD, lesogaberan, impedance, pharmacokinetics, safety, tolerability