Trial Outcomes & Findings for Esophageal Hypersensitivity Study in Patients With Gastroesophageal Reflux Disease (GERD) (NCT NCT01019928)

NCT ID: NCT01019928

Last Updated: 2012-11-09

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 14 participants
• Primary outcome timeframe: 1.5 hours post dose
• Results posted on: 2012-11-09

Participant Flow

A total of 30 patients were enrolled, 16 of these patients were NOT randomized for the following reasons: Voluntary discontinuation by patient = 3 Incorrect enrollment (did not meet inclusion/excl criteria) = 13

14 patients were randomised, 1 patient received placebo in the first treatment period without any events, but had an SAE prior to receiving AZD1386 in the second period and was withdrawn. 13 randomised patients completed the study, but one of these patients was incorrectly enrolled and excluded from the per-protocol analysis set.

Participant milestones

Measure	First AZD1386, Then Washout, Then Placebo	First Placebo, Then Washout, Then AZD1386
Period 1 STARTED	7	7
Period 1 COMPLETED	7	7
Period 1 NOT COMPLETED	0	0
Period 2 STARTED	7	7
Period 2 COMPLETED	7	6
Period 2 NOT COMPLETED	0	1
Period 3 STARTED	7	6
Period 3 COMPLETED	7	6
Period 3 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AZD1386 95 mg n=7 Participants	Placebo n=7 Participants	Total n=14 Participants Total of all reporting groups
Age Continuous Age (years)	54.9 years STANDARD_DEVIATION 15.0 • n=5 Participants	54.7 years STANDARD_DEVIATION 17.4 • n=7 Participants	54.8 years STANDARD_DEVIATION 16.2 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	AZD1386 95 mg n=12 Participants	Placebo n=13 Participants
Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 1.5 Hours Post-Dose.	84.0 seconds Interval 36.0 to 146.0	86.9 seconds Interval 29.0 to 127.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	AZD1386 95 mg n=12 Participants	Placebo n=13 Participants
Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 0.5 Hours Post Dose	86.0 seconds Interval 41.0 to 157.0	87.8 seconds Interval 31.0 to 132.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	AZD1386 95 mg n=12 Participants	Placebo n=13 Participants
Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 2.5 Hours Post Dose	85.5 seconds Interval 39.0 to 150.0	77.0 seconds Interval 24.0 to 125.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	AZD1386 95 mg n=12 Participants	Placebo n=13 Participants
Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 0.5 Hours Post Dose	16.2 ml Interval 8.0 to 37.0	15.1 ml Interval 6.0 to 41.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	AZD1386 95 mg n=12 Participants	Placebo n=13 Participants
Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 1.5 Hours Post-Dose	15.0 ml Interval 8.0 to 24.0	16.7 ml Interval 8.0 to 30.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	AZD1386 95 mg n=11 Participants	Placebo n=13 Participants
Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 2.5 Hours Post-Dose.	15.4 ml Interval 6.0 to 29.0	15.2 ml Interval 5.0 to 38.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	AZD1386 95 mg n=12 Participants	Placebo n=12 Participants
Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation 0.5 Hours Post Dose	16.7 mA Interval 9.0 to 31.0	16.7 mA Interval 9.0 to 40.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	AZD1386 95 mg n=12 Participants	Placebo n=12 Participants
Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation at 1.5 Hours Post Dose	16.7 mA Interval 8.0 to 30.0	15.8 mA Interval 8.0 to 37.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	AZD1386 95 mg n=11 Participants	Placebo n=12 Participants
Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation at 2.5 Hours Post Dose	16.2 mA Interval 8.0 to 31.0	14.8 mA Interval 8.0 to 28.0

SECONDARY outcome

Timeframe: 0 to 4 hours post dose

Area under the plasma concentration curve from time zero to the last quantifiable concentration

Outcome measures

Measure	AZD1386 95 mg n=12 Participants	Placebo
AUCt	5899 nmol*h/L Interval 4735.0 to 7349.0	—

SECONDARY outcome

Timeframe: 0 to 4 hours post dose

Maximum plasma concentration

Outcome measures

Measure	AZD1386 95 mg n=12 Participants	Placebo
Cmax	2361 nmol/L Interval 1859.0 to 3000.0	—

SECONDARY outcome

Timeframe: 0 to 4 hours post dose

Time of maximum plasma concentration

Outcome measures

Measure	AZD1386 95 mg n=12 Participants	Placebo
Tmax	1.0 hours Interval 0.5 to 2.5	—

SECONDARY outcome

Timeframe: 1.5 hours post dose

Supine Systolic Blood Pressure at 1.5 hours post dose

Outcome measures

Measure	AZD1386 95 mg n=13 Participants	Placebo n=14 Participants
SBP	145.8 mmHg Standard Deviation 10.3	139.7 mmHg Standard Deviation 12.7

SECONDARY outcome

Timeframe: 1.5 hours post dose

Supine Diastolic Blood Pressure at 1.5 hours post dose

Outcome measures

Measure	AZD1386 95 mg n=13 Participants	Placebo n=14 Participants
DBP	81.4 mmHg Standard Deviation 8.1	80.0 mmHg Standard Deviation 7.3

SECONDARY outcome

Timeframe: 1.5 hours post dose

Supine Pulse at 1.5 hours post dose

Outcome measures

Measure	AZD1386 95 mg n=13 Participants	Placebo n=14 Participants
Pulse	67.8 beats/min Standard Deviation 12.9	62.2 beats/min Standard Deviation 9.4

SECONDARY outcome

Timeframe: 1.5 hours post dose

QT interval corrected for heart rate using Fredericia formula(QTcF) at 1.5 hours post dose

Outcome measures

Measure	AZD1386 95 mg n=13 Participants	Placebo n=14 Participants
QTcF	409.6 ms Standard Deviation 19.0	414.3 ms Standard Deviation 17.3

SECONDARY outcome

Timeframe: 1.5 hours post dose

Oral Body Temperature at 1.5 hours post dose

Outcome measures

Measure	AZD1386 95 mg n=13 Participants	Placebo n=14 Participants
Body Temperature	37.2 degrees Celsius Standard Deviation 0.4	36.8 degrees Celsius Standard Deviation 0.3

SECONDARY outcome

Timeframe: Pre-entry to follow-up

Number of participants with clinically relevant change of laboratory variables(clinical chemistry, haematology and urinalysis parameters)

Outcome measures

Measure	AZD1386 95 mg n=13 Participants	Placebo n=14 Participants
Clinically Relevant Change of Laboratory Variables	0 Participants	0 Participants

Adverse Events

AZD1386 95 mg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	AZD1386 95 mg n=13 participants at risk	Placebo n=14 participants at risk
Cardiac disorders ECG, atrial fibrillation	0.00% 0/13	7.1% 1/14

Other adverse events

Measure	AZD1386 95 mg n=13 participants at risk	Placebo n=14 participants at risk
General disorders Feeling Cold	53.8% 7/13	0.00% 0/14
General disorders Chills	7.7% 1/13	0.00% 0/14
General disorders Feeling Of Body Temperature Change	7.7% 1/13	0.00% 0/14
General disorders Pain	0.00% 0/13	7.1% 1/14
General disorders Hypoaesthesia Oral	23.1% 3/13	0.00% 0/14
Gastrointestinal disorders Dyspepsia	0.00% 0/13	7.1% 1/14
Gastrointestinal disorders Nausea	7.7% 1/13	0.00% 0/14
Gastrointestinal disorders Oesophageal Disorder	7.7% 1/13	0.00% 0/14
Gastrointestinal disorders Vomiting	7.7% 1/13	0.00% 0/14
Investigations Body Temperature Increased	30.8% 4/13	0.00% 0/14
Nervous system disorders Ageusia	7.7% 1/13	0.00% 0/14
Nervous system disorders Burning Sensation	7.7% 1/13	0.00% 0/14
Nervous system disorders Dysgeusia	7.7% 1/13	0.00% 0/14
Nervous system disorders Headache	7.7% 1/13	0.00% 0/14
Nervous system disorders Paraesthesia	7.7% 1/13	0.00% 0/14
Respiratory, thoracic and mediastinal disorders Throat Irritation	15.4% 2/13	0.00% 0/14
Injury, poisoning and procedural complications Arthropod Sting	7.7% 1/13	0.00% 0/14
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	7.7% 1/13	0.00% 0/14
General disorders Peripheral Coldness	7.7% 1/13	0.00% 0/14

Additional Information

Gerard Lynch

AstraZeneca

Phone: +44 1625 518062

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60