TLESR-impedance study in patients

Study identifier:D9120C00020

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A double-blind, placebo controlled, randomized, two centre phase IIA pharmacodynamic cross-over study to assess the effect of AZD3355, 65 mg bid, on transient lower esophageal sphincter relaxations (TLESRs) in GERD patients with an incomplete response to PPI treatment

Medical condition

Reflux episodes

Phase

Phase 2

Healthy volunteers

Study drug

AZD3355, Placebo

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 70 Years

Date

Study Start Date: 01 Feb 2007

Primary Completion Date: 01 Feb 2008

Study Completion Date: 01 Feb 2008

Study design

Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind
Primary Purpose: Basic Science

Verification:

Verified 01 May 2011 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

No locations available

Arms	Assigned Interventions
Experimental: 1 AZD3355	Drug: AZD3355 65 mg capsules, oral, 3 single doses Other Name: Lesogaberan
Placebo Comparator: 2	Drug: Placebo capsules, oral, 3 single doses

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
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

Participant Flow for 3 periods

Period 1: First Intervention

	AZD3355 first, then Placebo	Placebo first, then AZD3355
STARTED	14	13
COMPLETED	14	12
NOT COMPLETED	0	1
Catheter placement problems	0	1

Period 2: Washout Period

	AZD3355 first, then Placebo	Placebo first, then AZD3355
STARTED	14	12
COMPLETED	14	11
NOT COMPLETED	0	1
Adverse Event	0	1

Period 3: Second Intervention

	AZD3355 first, then Placebo	Placebo first, then AZD3355
STARTED	14	11
COMPLETED	14	11
NOT COMPLETED	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Entire Study Population	Includes groups randomized to received Drug first and Placebo first.

Baseline Measures

	Entire Study Population
Number of Participants [units: Participants]	27
Age Continuous [units: years] Mean ± Standard Deviation	51.6 ± 10.2
Gender, Male/Female [units: Participants]
Female	11
Male	16

Outcome Measures

1. Primary Outcome Measure: Number of transient lower esophageal sphincter relaxations (TLESRs) 0-3 hours post meal, post third dose [ Time Frame: 0-3 hours post meal, post third dose ]

Measure Type	Primary
Measure Name	Number of transient lower esophageal sphincter relaxations (TLESRs) 0-3 hours post meal, post third dose
Measure Description	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.
Time Frame	0-3 hours post meal, post third dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
AZD3355	65 mg drug capsules, oral, 3 single doses
Placebo	placebo capsules, oral, 3 single doses

Measured Values

	AZD3355	Placebo
Number of Participants Analyzed [units:participants]	21	21
Number of transient lower esophageal sphincter relaxations (TLESRs) 0-3 hours post meal, post third dose [units: Relaxations] Geometric Mean (95% Confidence Interval)	11.6 (9.40 to 14.3)	15.5 (12.6 to 19.1)

No statistical analysis provided for Number of transient lower esophageal sphincter relaxations (TLESRs) 0-3 hours post meal, post third dose

2. Secondary Outcome Measure: Total number reflux episodes 0-24 hours post first dose [ Time Frame: 0-24 hours ]

Measure Type	Secondary
Measure Name	Total number reflux episodes 0-24 hours post first dose
Measure Description	Number of reflux episodes assessed during the 24-hour ambulatory impedance-pH recording.
Time Frame	0-24 hours
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
AZD3355	65 mg drug capsules, oral, 3 single doses
Placebo	placebo capsules, oral, 3 single doses

Measured Values

	AZD3355	Placebo
Number of Participants Analyzed [units:participants]	21	21
Total number reflux episodes 0-24 hours post first dose [units: Episodes] Geometric Mean (95% Confidence Interval)	30.6 (20.9 to 44.9)	50.5 (34.5 to 74.1)

No statistical analysis provided for Total number reflux episodes 0-24 hours post first dose

3. Secondary Outcome Measure: Area under the plasma concentration vs. time curve (AUCtau) during 0-12 hours post first dose calculated by the log/linear trapezoidal method. [ Time Frame: 0-12 hours post first dose ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration vs. time curve (AUCtau) during 0-12 hours post first dose calculated by the log/linear trapezoidal method.
Measure Description	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.
Time Frame	0-12 hours post first dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
AZD3355	65 mg drug capsules, oral, 3 single doses

Measured Values

	AZD3355
Number of Participants Analyzed [units:participants]	24
Area under the plasma concentration vs. time curve (AUCtau) during 0-12 hours post first dose calculated by the log/linear trapezoidal method. [units: μmol*hours / L] Geometric Mean (Standard Deviation)	7.16 (2.36)

No statistical analysis provided for Area under the plasma concentration vs. time curve (AUCtau) during 0-12 hours post first dose calculated by the log/linear trapezoidal method.

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
AZD3355	65 mg drug capsules, oral, 3 single doses
Placebo	placebo capsules, oral, 3 single doses

Serious Adverse Events

	AZD3355	Placebo
Total, serious adverse events
# participants affected / at risk	0/25 (0.00%)	0/27 (0.00%)

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
AZD3355	65 mg drug capsules, oral, 3 single doses
Placebo	placebo capsules, oral, 3 single doses