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Trial Outcomes & Findings for TLESR-impedance Study in Patients (NCT NCT00743444)

NCT ID: NCT00743444

Last Updated: 2013-07-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

0-3 hours post meal, post third dose

Results posted on

2013-07-22

Participant Flow

42 patients in 2 countries were enrolled in the study. 27 patients were randomised to treatment. 2 patients discontinued prematurely, 1 due to low Lower Esophageal Sphincter Pressure (LESP)/catheter placement problems, and 1 due to nausea/vomiting. Thus, 25 patients completed the study, 10 in Belgium and 15 in the Netherlands.

Participant milestones

Participant milestones
Measure
AZD3355 First, Then Placebo
65 mg drug or placebo capsules, oral, 3 single doses
Placebo First, Then AZD3355
65 mg drug or placebo capsules, oral, 3 single doses
First Intervention
STARTED
14
13
First Intervention
COMPLETED
14
12
First Intervention
NOT COMPLETED
0
1
Washout Period
STARTED
14
12
Washout Period
COMPLETED
14
11
Washout Period
NOT COMPLETED
0
1
Second Intervention
STARTED
14
11
Second Intervention
COMPLETED
14
11
Second Intervention
NOT COMPLETED
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
AZD3355 First, Then Placebo
65 mg drug or placebo capsules, oral, 3 single doses
Placebo First, Then AZD3355
65 mg drug or placebo capsules, oral, 3 single doses
First Intervention
Catheter placement problems
0
1
Washout Period
Adverse Event
0
1

Baseline Characteristics

TLESR-impedance Study in Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Entire Study Population
n=27 Participants
Includes groups randomized to received Drug first and Placebo first.
Age Continuous
51.6 years
STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male
Female
11 Participants
n=5 Participants
Sex: Female, Male
Male
16 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 0-3 hours post meal, post third dose

Population: Per Protocol Analysis Set (PP). From the safety analysis set with 27 patients, the PP excludes 2 patients since they discontinued prematurely from the study. Additionally, 4 patients were excluded from the primary analysis; 1 due to catheter placement problems, 1 due to error in dose administration, 1 due to low LESP, 1 due to multiple swallowing.

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.

Outcome measures

Outcome measures
Measure
AZD3355
n=21 Participants
65 mg drug capsules, oral, 3 single doses
Placebo
n=21 Participants
placebo capsules, oral, 3 single doses
Number of Transient Lower Esophageal Sphincter Relaxations (TLESRs) 0-3 Hours Post Meal, Post Third Dose
11.6 Relaxations
Interval 9.4 to 14.3
15.5 Relaxations
Interval 12.6 to 19.1

SECONDARY outcome

Timeframe: 0-24 hours

Population: Per Protocol Analysis Set (PP). From the safety analysis set with 27 patients, the PP excludes 2 patients since they discontinued prematurely from the study. Additionally, 4 patients were excluded from this analysis; 1 due to catheter placement problems, 1 due to error in dose administration, 2 due to insufficient impedance/pH recording time.

Number of reflux episodes assessed during the 24-hour ambulatory impedance-pH recording.

Outcome measures

Outcome measures
Measure
AZD3355
n=21 Participants
65 mg drug capsules, oral, 3 single doses
Placebo
n=21 Participants
placebo capsules, oral, 3 single doses
Total Number Reflux Episodes 0-24 Hours Post First Dose
30.6 Episodes
Interval 20.9 to 44.9
50.5 Episodes
Interval 34.5 to 74.1

SECONDARY outcome

Timeframe: 0-12 hours post first dose

Population: Per Protocol Analysis Set (PP). From the safety analysis set with 27 patients, the PP excludes 2 patients since they discontinued prematurely from the study. Additionally, 1 patient was excluded from the pharmacokinetic analysis due to error in dose administration at dose 2.

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.

Outcome measures

Outcome measures
Measure
AZD3355
n=24 Participants
65 mg drug capsules, oral, 3 single doses
Placebo
placebo capsules, oral, 3 single doses
Area Under the Plasma Concentration vs. Time Curve (AUCtau) During 0-12 Hours Post First Dose Calculated by the Log/Linear Trapezoidal Method.
7.16 μmol*hours / L
Standard Deviation 2.36
—

Adverse Events

AZD3355

Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
AZD3355
n=25 participants at risk
65 mg drug capsules, oral, 3 single doses
Placebo
n=27 participants at risk
placebo capsules, oral, 3 single doses
Gastrointestinal disorders
Abdominal Distension
12.0%
3/25
3.7%
1/27
Gastrointestinal disorders
Nausea
8.0%
2/25
18.5%
5/27
Infections and infestations
Nasopharyngitis
4.0%
1/25
7.4%
2/27
Nervous system disorders
Dizziness
12.0%
3/25
3.7%
1/27
Nervous system disorders
Headache
32.0%
8/25
40.7%
11/27
Nervous system disorders
Paraesthesia
20.0%
5/25
11.1%
3/27
Skin and subcutaneous tissue disorders
Hyperhidrosis
0.00%
0/25
7.4%
2/27
Vascular disorders
Hot Flush
12.0%
3/25
3.7%
1/27
Gastrointestinal disorders
Flatulence
8.0%
2/25
3.7%
1/27
General disorders
Feeling Hot
8.0%
2/25
3.7%
1/27

Additional Information

Gerard Lynch

AstraZeneca

Results disclosure agreements

  • Principal investigator is a sponsor employee There is an agreement between PI and Sponsor (AZ) or its agents that restricts the PI's right to discuss/publish trial results after the trial is completed. The PI agrees to collaborate in good faith with AZ with regards to content and formation of any publication or disclosure to be made by PI and to pay due consideration to opinions offered by AZ.
  • Publication restrictions are in place

Restriction type: OTHER