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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01019928
First received: November 20, 2009
Last updated: October 10, 2012
Last verified: October 2012
  Purpose

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


Condition Intervention Phase
Sensitivity in Esophagus
Drug: AZD1386
Drug: Placebo to AZD1386
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 1.5 Hours Post-Dose. [ Time Frame: 1.5 hours post dose ] [ Designated as safety issue: No ]

    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:
  • Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 0.5 Hours Post Dose [ Time Frame: 0.5 hours post dose ] [ Designated as safety issue: No ]

    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 [ Time Frame: 2.5 hours post dose ] [ Designated as safety issue: No ]

    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 [ Time Frame: 0.5 hours post dose ] [ Designated as safety issue: No ]

    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 [ Time Frame: 1.5 hours post dose ] [ Designated as safety issue: No ]

    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. [ Time Frame: 2.5 hours post dose ] [ Designated as safety issue: No ]

    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 [ Time Frame: 0.5 hours post dose ] [ Designated as safety issue: No ]

    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 [ Time Frame: 1.5 hours post dose ] [ Designated as safety issue: No ]

    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 [ Time Frame: 2.5 hours post dose ] [ Designated as safety issue: No ]

    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 [ Time Frame: 0 to 4 hours post dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration curve from time zero to the last quantifiable concentration

  • Cmax [ Time Frame: 0 to 4 hours post dose ] [ Designated as safety issue: No ]
    Maximum plasma concentration

  • Tmax [ Time Frame: 0 to 4 hours post dose ] [ Designated as safety issue: No ]
    Time of maximum plasma concentration

  • SBP [ Time Frame: 1.5 hours post dose ] [ Designated as safety issue: Yes ]
    Supine Systolic Blood Pressure at 1.5 hours post dose

  • DBP [ Time Frame: 1.5 hours post dose ] [ Designated as safety issue: Yes ]
    Supine Diastolic Blood Pressure at 1.5 hours post dose

  • Pulse [ Time Frame: 1.5 hours post dose ] [ Designated as safety issue: Yes ]
    Supine Pulse at 1.5 hours post dose

  • QTcF [ Time Frame: 1.5 hours post dose ] [ Designated as safety issue: Yes ]
    QT interval corrected for heart rate using Fredericia formula(QTcF) at 1.5 hours post dose

  • Body Temperature [ Time Frame: 1.5 hours post dose ] [ Designated as safety issue: Yes ]
    Oral Body Temperature at 1.5 hours post dose

  • Clinically Relevant Change of Laboratory Variables [ Time Frame: Pre-entry to follow-up ] [ Designated as safety issue: Yes ]
    Number of participants with clinically relevant change of laboratory variables(clinical chemistry, haematology and urinalysis parameters)


Enrollment: 14
Study Start Date: November 2009
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: First AZD1386, then washout, then placebo Drug: AZD1386
95 mg, oral solution, single dose
Drug: Placebo to AZD1386
Placebo, oral solution, single dose
Experimental: First placebo, then washout, then AZD1386 Drug: AZD1386
95 mg, oral solution, single dose
Drug: Placebo to AZD1386
Placebo, oral solution, single dose

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01019928

Locations
Denmark
Research Site
Århus C, Denmark
Sweden
Research Site
Goteborg, Vastra Gotaland, Sweden
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Marie Sundin AstraZeneca R&D Mölndal, Sweden
Principal Investigator: Peter Funch-Jensen,, MD, PhD Aarhus Hospital, Dept of Surgical Gastroenterology, Aarhus, Denmark
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01019928     History of Changes
Other Study ID Numbers: D9127C00002, 2008-007420-26
Study First Received: November 20, 2009
Results First Received: January 27, 2012
Last Updated: October 10, 2012
Health Authority: Denmark: Danish Medicines Agency
Sweden: Medical Products Agency

Keywords provided by AstraZeneca:
GERD
patient
esophagus
pain

Additional relevant MeSH terms:
Gastroesophageal Reflux
Hypersensitivity
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 24, 2014