TLESR-impedance Study in Patients

This study has been completed.

Sponsor:

Information provided by:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT00743444

First received: August 26, 2008

Last updated: May 10, 2011

Last verified: May 2011

History of Changes

Results First Received: March 16, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Crossover Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
Condition:	Reflux Episodes
Interventions:	Drug: AZD3355 Drug: Placebo

Participant Flow

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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

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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 [units: years] Mean ± Standard Deviation	51.6 ± 10.2
Gender [units: Participants]
Female	11
Male	16

Outcome Measures

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1. Primary:

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 Title	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:

Total Number Reflux Episodes 0-24 Hours Post First Dose [ Time Frame: 0-24 hours ]

Measure Type	Secondary
Measure Title	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:

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 Title	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

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Gerard Lynch
Organization: AstraZeneca
e-mail: ClinicalTrialTransparency@astrazeneca.com

No publications provided by AstraZeneca

Publications automatically indexed to this study:

Boeckxstaens GE, Beaumont H, Mertens V, Denison H, Ruth M, Adler J, Silberg DG, Sifrim D. Effects of lesogaberan on reflux and lower esophageal sphincter function in patients with gastroesophageal reflux disease. Gastroenterology. 2010 Aug;139(2):409-17. Epub 2010 May 5.

Responsible Party:	Debra Silberg, MD PhD, Medical Science Director, AZD3355, AstraZeneca Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00743444 History of Changes
Other Study ID Numbers:	D9120C00020
Study First Received:	August 26, 2008
Results First Received:	March 16, 2011
Last Updated:	May 10, 2011
Health Authority:	Belgium: Federal Agency for Medicinal Products and Health Products

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