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

Phase 2

Completed

• Conditions: Sensitivity in Esophagus
• Interventions: Drug: AZD1386; Drug: Placebo to AZD1386

• Registration Number: NCT01019928
• Lead Sponsor: AstraZeneca

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11
• Study First Submitted: 2009-11-20
• Study First Submitted QC: 2009-11-24
• Study First Posted: 2009-11-25
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Results First Submitted: 2012-01-27
• Status Verified: 2012-10
• Results First Submitted QC: 2012-10-10
• Last Update Submitted: 2012-10-10
• Results First Posted: 2012-11-09
• Last Update Posted: 2012-11-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
First AZD1386, then washout, then placebo	AZD1386	-
First AZD1386, then washout, then placebo	Placebo to AZD1386	-
First placebo, then washout, then AZD1386	AZD1386	-
First placebo, then washout, then AZD1386	Placebo to AZD1386	-

Primary Outcome Measures

Name	Time	Method
Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 1.5 Hours Post-Dose.	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: 1. = vague perception of mild sensation; 2. = definite perception of mild sensation; 3. = vague perception of moderate sensation; 4. = definite perception of moderate sensation; For painful sensations the patients will use the scale from 5-10 anchored at: 5. = pain detection; 6. = slight pain; 7. = moderate pain; 8. = medium pain intensity; 9. = intense pain; 10. = unbearable pain

Secondary Outcome Measures

Name	Time	Method
Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 0.5 Hours Post Dose	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: 1. = vague perception of mild sensation; 2. = definite perception of mild sensation; 3. = vague perception of moderate sensation; 4. = definite perception of moderate sensation; For painful sensations the patients will use the scale from 5-10 anchored at: 5. = pain detection; 6. = slight pain; 7. = moderate pain; 8. = medium pain intensity; 9. = intense pain; 10. = unbearable pain
Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 2.5 Hours Post Dose	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: 1. = vague perception of mild sensation; 2. = definite perception of mild sensation; 3. = vague perception of moderate sensation; 4. = definite perception of moderate sensation; For painful sensations the patients will use the scale from 5-10 anchored at: 5. = pain detection; 6. = slight pain; 7. = moderate pain; 8. = medium pain intensity; 9. = intense pain; 10. = unbearable pain
Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 0.5 Hours Post Dose	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: 1. = vague perception of mild sensation; 2. = definite perception of mild sensation; 3. = vague perception of moderate sensation; 4. = definite perception of moderate sensation; For painful sensations the patients will use the scale from 5-10 anchored at: 5. = pain detection; 6. = slight pain; 7. = moderate pain; 8. = medium pain intensity; 9. = intense pain; 10. = unbearable pain
Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 1.5 Hours Post-Dose	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: 1. = vague perception of mild sensation; 2. = definite perception of mild sensation; 3. = vague perception of moderate sensation; 4. = definite perception of moderate sensation; For painful sensations the patients will use the scale from 5-10 anchored at: 5. = pain detection; 6. = slight pain; 7. = moderate pain; 8. = medium pain intensity; 9. = intense pain; 10. = unbearable pain
Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 2.5 Hours Post-Dose.	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: 1. = vague perception of mild sensation; 2. = definite perception of mild sensation; 3. = vague perception of moderate sensation; 4. = definite perception of moderate sensation; For painful sensations the patients will use the scale from 5-10 anchored at: 5. = pain detection; 6. = slight pain; 7. = moderate pain; 8. = medium pain intensity; 9. = intense pain; 10. = unbearable pain
Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation 0.5 Hours Post Dose	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: 1. = vague perception of mild sensation; 2. = definite perception of mild sensation; 3. = vague perception of moderate sensation; 4. = definite perception of moderate sensation; For painful sensations the patients will use the scale from 5-10 anchored at: 5. = pain detection; 6. = slight pain; 7. = moderate pain; 8. = medium pain intensity; 9. = intense pain; 10. = unbearable pain
Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation at 1.5 Hours Post Dose	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: 1. = vague perception of mild sensation; 2. = definite perception of mild sensation; 3. = vague perception of moderate sensation; 4. = definite perception of moderate sensation; For painful sensations the patients will use the scale from 5-10 anchored at: 5. = pain detection; 6. = slight pain; 7. = moderate pain; 8. = medium pain intensity; 9. = intense pain; 10. = unbearable pain
Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation at 2.5 Hours Post Dose	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: 1. = vague perception of mild sensation; 2. = definite perception of mild sensation; 3. = vague perception of moderate sensation; 4. = definite perception of moderate sensation; For painful sensations the patients will use the scale from 5-10 anchored at: 5. = pain detection; 6. = slight pain; 7. = moderate pain; 8. = medium pain intensity; 9. = intense pain; 10. = unbearable pain
AUCt	0 to 4 hours post dose	Area under the plasma concentration curve from time zero to the last quantifiable concentration
Cmax	0 to 4 hours post dose	Maximum plasma concentration
Tmax	0 to 4 hours post dose	Time of maximum plasma concentration
SBP	1.5 hours post dose	Supine Systolic Blood Pressure at 1.5 hours post dose
DBP	1.5 hours post dose	Supine Diastolic Blood Pressure at 1.5 hours post dose
Pulse	1.5 hours post dose	Supine Pulse at 1.5 hours post dose
QTcF	1.5 hours post dose	QT interval corrected for heart rate using Fredericia formula(QTcF) at 1.5 hours post dose
Body Temperature	1.5 hours post dose	Oral Body Temperature at 1.5 hours post dose
Clinically Relevant Change of Laboratory Variables	Pre-entry to follow-up	Number of participants with clinically relevant change of laboratory variables(clinical chemistry, haematology and urinalysis parameters)

Trial Locations

Locations (1)

Research Site; 🇸🇪 Goteborg, Vastra Gotaland, Sweden