TLESR-impedance Study in Patients

Study Overview
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Brief Summary
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The purpose of the study is to compare frequency and content of reflux episodes in patients with gastroesophageal reflux disease.

Official Title
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A Double-blind, Placebo Controlled, Randomized, Two Centre Phase IIA Pharmacodynamic Cross-over Study to Assess the Effect of AZD3355, 65 mg Bid, on Transient Lower Esophageal Sphincter Relaxations (TLESRs) in GERD Patients With an Incomplete Response to PPI Treatment

Conditions
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Reflux Episodes

Intervention / Treatment
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* Drug: AZD3355
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written consent GERD patients, age 18-70 years, females must be postmenopausal or surgically sterilised 6 months history of GERD and incomplete response to PPI treatment Exclusion Criteria: Insufficient symptom burden of the reflux disease evaluated by questionnaires S-creatinine >1.2 times upper limit of normal History of heart disease Prior surgery of the upper GI tract

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD3355 | Drug: AZD3355<br>* 65 mg capsules, oral, 3 single doses<br>* Other names: Lesogaberan;|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* capsules, oral, 3 single doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Transient Lower Esophageal Sphincter Relaxations (TLESRs) 0-3 Hours Post Meal, Post Third Dose | The number of relaxations for each patient in each period was determined from manometric tracings according to previously published criteria (R.H. Holloway, R. Penagini and A.C. Ireland, Criteria for objective definition of transient lower esophageal sphincter relaxation, Am J Physiol 268 (1995), pp. G128-G133). The analysis of the number of TLESRs was based on an analysis of variance (ANOVA) for log-transformed data. The 95% level confidence interval (CI) limits were transformed back to the original scale to give CIs for the geometric mean for each treatment. | 0-3 hours post meal, post third dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number Reflux Episodes 0-24 Hours Post First Dose | Number of reflux episodes assessed during the 24-hour ambulatory impedance-pH recording. | 0-24 hours | 
| Area Under the Plasma Concentration vs. Time Curve (AUCtau) During 0-12 Hours Post First Dose Calculated by the Log/Linear Trapezoidal Method. | The AUCtau was calculated for each patient in the period with AZD3355 treatment by the Log-Linear Trapezoidal Method. The descriptive geometric mean of the individual AUCtau values is reported here. | 0-12 hours post first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GERD, transient lower esophageal sphincter relaxations (TLESRs), reflux