Esophageal Hypersensitivity Study in Patients With Gastroesophageal Reflux Disease (GERD)

Study Overview
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Brief Summary
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The purpose of the study is to compare sensitivity of visceral pain in the esophagus using different pain stimuli.

Official Title
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A Phase IIa, Double-blind, Randomized, 2-way Cross-over Study to Evaluate the Effect of a Single Dose of AZD1386 95 mg Compared to Placebo in a Multimodal Experimental Pain Model on Esophageal Sensitivity in GERD Patients With a Partial Response to PPI Treatment

Conditions
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Sensitivity in Esophagus

Intervention / Treatment
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* Drug: AZD1386
* Drug: Placebo to AZD1386


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed informed consent form BMI 18.5-35.0, inclusive Continuous PPI treatment for GERD during the last 4 weeks Exclusion Criteria: Patients that have not experienced any GERD symptoms improvement at all after PPI treatment Unstable or clinically significant disorders including cardiovascular, respiratory, renal, hepatic, metabolic, psychiatric, other gastrointestinal and esophageal disorders besides GERD 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: First AZD1386, then washout, then placebo<br> | Drug: AZD1386<br>* 95 mg, oral solution, single dose<br>Drug: Placebo to AZD1386<br>* Placebo, oral solution, single dose<br>|
| Experimental: First placebo, then washout, then AZD1386<br> | Drug: AZD1386<br>* 95 mg, oral solution, single dose<br>Drug: Placebo to AZD1386<br>* Placebo, oral solution, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 1.5 Hours Post-Dose. | A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Heat stimuli were applied by recirculation of heated water in the bag. Prior to recirculation the bag is filled with 7mL to ensure adequate mucosal contact. Water was heated up to a maximum of 63° C and the stimulation was continued until VAS 7 was reached. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain | 1.5 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 0.5 Hours Post Dose | A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Heat stimuli were applied by recirculation of heated water in the bag. Prior to recirculation the bag is filled with 7mL to ensure adequate mucosal contact. Water was heated up to a maximum of 63° C and the stimulation was continued until VAS 7 was reached. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain | 0.5 hours post dose | 
| Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 2.5 Hours Post Dose | A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Heat stimuli were applied by recirculation of heated water in the bag. Prior to recirculation the bag is filled with 7mL to ensure adequate mucosal contact. Water was heated up to a maximum of 63° C and the stimulation was continued until VAS 7 was reached. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain | 2.5 hours post dose | 
| Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 0.5 Hours Post Dose | A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Volume change in the bag was recorded continuously at each level of the visual analogue scale (VAS) and up to VAS7 (Volume at Visual Analogue Scale 7). The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain | 0.5 hours post dose | 
| Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 1.5 Hours Post-Dose | A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Volume change in the bag was recorded continuously at each level of the visual analogue scale (VAS) and up to VAS7 (Volume at Visual Analogue Scale 7). The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain | 1.5 hours post dose | 
| Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 2.5 Hours Post-Dose. | A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Volume change in the bag was recorded continuously at each level of the visual analogue scale (VAS) and up to VAS7 (Volume at Visual Analogue Scale 7). The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain | 2.5 hours post dose | 
| Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation 0.5 Hours Post Dose | A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES) and stimulations were performed at approximately 8 cm above the LES. The intensity of the stimuli is increased steadily in steps of 0.5 to 1 mA and the intensity corresponding to the VAS levels 1, 3, 5 and 7 were recorded. The current will be increased until the patient report moderate pain (VAS 7) or max 80 mA. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain | 0.5 hours post dose | 
| Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation at 1.5 Hours Post Dose | A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES) and stimulations were performed at approximately 8 cm above the LES. The intensity of the stimuli is increased steadily in steps of 0.5 to 1 mA and the intensity corresponding to the VAS levels 1, 3, 5 and 7 were recorded. The current will be increased until the patient report moderate pain (VAS 7) or max 80 mA. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain | 1.5 hours post dose | 
| Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation at 2.5 Hours Post Dose | A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES) and stimulations were performed at approximately 8 cm above the LES. The intensity of the stimuli is increased steadily in steps of 0.5 to 1 mA and the intensity corresponding to the VAS levels 1, 3, 5 and 7 were recorded. The current will be increased until the patient report moderate pain (VAS 7) or max 80 mA. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain | 2.5 hours post dose | 
| AUCt | Area under the plasma concentration curve from time zero to the last quantifiable concentration | 0 to 4 hours post dose | 
| Cmax | Maximum plasma concentration | 0 to 4 hours post dose | 
| Tmax | Time of maximum plasma concentration | 0 to 4 hours post dose | 
| SBP | Supine Systolic Blood Pressure at 1.5 hours post dose | 1.5 hours post dose | 
| DBP | Supine Diastolic Blood Pressure at 1.5 hours post dose | 1.5 hours post dose | 
| Pulse | Supine Pulse at 1.5 hours post dose | 1.5 hours post dose | 
| QTcF | QT interval corrected for heart rate using Fredericia formula(QTcF) at 1.5 hours post dose | 1.5 hours post dose | 
| Body Temperature | Oral Body Temperature at 1.5 hours post dose | 1.5 hours post dose | 
| Clinically Relevant Change of Laboratory Variables | Number of participants with clinically relevant change of laboratory variables(clinical chemistry, haematology and urinalysis parameters) | Pre-entry to follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GERD, patient, esophagus, pain