Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants with persisting symptoms of Gastroesophageal Reflux Disease (GORD) despite previous treatment with a full dose proton pump inhibitor were enrolled across the Argentina (6 sites), Chile (3 sites) Colombia (9 sites) and Venezuela (2 sites).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All participants received 8-weeks open label esomeprazole treatment.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Participant Flow for 2 periods

Period 1: Screening

	Esomeprazole 40mg, daily
STARTED	337
COMPLETED	317^[1]
NOT COMPLETED	20
Protocol Violation	12
Withdrawal by Subject	5
Lost to Follow-up	2
Unconfirmed pregnancy	1

[1]	20 participants were screening failure.

Period 2: Open Label

	Esomeprazole 40mg, daily
STARTED	317^[1]
Safety Analysis	317
Full Analysis	311
Per Protocol	301
COMPLETED	301^[2]
NOT COMPLETED	16
Lost to Follow-up	7
Withdrawal by Subject	5
Protocol Violation	4

[1]	Full analysis performed in 311
[2]	16 patients discontinued after randomization

Baseline Characteristics

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

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Baseline Measures

	Esomeprazole 40mg, daily
Number of Participants [units: Participants]	311
Age Continuous ^[1] [units: Years] Mean ± Standard Deviation	42.7 ± 14.3
Gender, Male/Female ^[2] [units: Participants]
Female	212
Male	99

Outcome Measures

1. Primary Outcome Measure: Change in Frequency of days with Heartburn from baseline to 8 weeks of treatment [ Time Frame: At Baseline and 8 weeks ]

Measure Type	Primary
Measure Name	Change in Frequency of days with Heartburn from baseline to 8 weeks of treatment
Measure Description	Reported frequency of days with heartburn at week 8 - reported frequency of days with heartburn at baseline
Time Frame	At Baseline and 8 weeks
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.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Measured Values

	Esomeprazole 40mg, daily
Number of Participants Analyzed [units:participants]	311
Change in Frequency of days with Heartburn from baseline to 8 weeks of treatment [units: Days per week with symptoms] Mean (Standard Deviation)	-3.44 (2.35)

No statistical analysis provided for Change in Frequency of days with Heartburn from baseline to 8 weeks of treatment

2. Secondary Outcome Measure: Change in Frequency of days with Heartburn from baseline to 4 weeks of treatment [ Time Frame: At Baseline and 4 weeks ]

Measure Type	Secondary
Measure Name	Change in Frequency of days with Heartburn from baseline to 4 weeks of treatment
Measure Description	Reported frequency of days with heartburn at week 4 - reported frequency of days with heartburn at baseline.
Time Frame	At Baseline and 4 weeks
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.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Measured Values

	Esomeprazole 40mg, daily
Number of Participants Analyzed [units:participants]	311
Change in Frequency of days with Heartburn from baseline to 4 weeks of treatment [units: Days per week with symptoms] Mean (Standard Deviation)	-3.08 (2.32)

No statistical analysis provided for Change in Frequency of days with Heartburn from baseline to 4 weeks of treatment

3. Secondary Outcome Measure: Change in Severity of Heartburn from baseline to 8 weeks of treatment [ Time Frame: At Baseline and 8 weeks ]

Measure Type	Secondary
Measure Name	Change in Severity of Heartburn from baseline to 8 weeks of treatment
Measure Description	Reported severity of heartburn at week 8 on RDQ - reported severity of heartburn at baseline on RDQ RDQ: Reflux Disease Questionnaire - by AstraZeneca LLP, 2000, values from "None" to "Severe". Four dimensions are defined for the RDQ – heartburn, regurgitation, GORD dimension and dyspepsia: stomach. Scores for each dimension are range from 0 to 5 for frequency (not present to daily) and/or severity (not present to severe).
Time Frame	At Baseline and 8 weeks
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.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Measured Values

	Esomeprazole 40mg, daily
Number of Participants Analyzed [units:participants]	311
Change in Severity of Heartburn from baseline to 8 weeks of treatment [units: Units of scale] Mean (Standard Deviation)	-1.56 (1.01)

No statistical analysis provided for Change in Severity of Heartburn from baseline to 8 weeks of treatment

4. Secondary Outcome Measure: Change in Severity of Heartburn from baseline to 4 weeks of treatment [ Time Frame: At Baseline and 4 weeks ]

Measure Type	Secondary
Measure Name	Change in Severity of Heartburn from baseline to 4 weeks of treatment
Measure Description	Reported severity of heartburn at week 4 on RDQ - reported severity of heartburn at baseline on RDQ (RDQ: Reflux Disease Questionnaire - by AstraZeneca LLP, 2000, values from "None" to "Severe". Four dimensions are defined for the RDQ – heartburn, regurgitation, GORD dimension and dyspepsia: stomach. Scores for each dimension are range from 0 to 5 for frequency (not present to daily) and/or severity (not present to severe).
Time Frame	At Baseline and 4 weeks
Safety Issue?	Yes

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.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Measured Values

	Esomeprazole 40mg, daily
Number of Participants Analyzed [units:participants]	311
Change in Severity of Heartburn from baseline to 4 weeks of treatment [units: Units on scale] Mean (Standard Deviation)	-1.34 (1.03)

No statistical analysis provided for Change in Severity of Heartburn from baseline to 4 weeks of treatment

5. Secondary Outcome Measure: Change in Frequency of days with Acid Regurgitation from baseline to 4 weeks of treatment. [ Time Frame: At Baseline and 4 weeks. ]

Measure Type	Secondary
Measure Name	Change in Frequency of days with Acid Regurgitation from baseline to 4 weeks of treatment.
Measure Description	Reported frequency of days with Acid regurgitation at week 4 - reported frequency of days with acid regurgitation at baseline. Four dimensions are defined for the Reflux Disease Questionnaire (RDQ) – heartburn, regurgitation, GORD dimension and dyspepsia: stomach. Scores for each dimension are range from 0 to 5 for frequency (not present to daily) and/or severity (not present to severe).
Time Frame	At Baseline and 4 weeks.
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.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Measured Values

	Esomeprazole 40mg, daily
Number of Participants Analyzed [units:participants]	311
Change in Frequency of days with Acid Regurgitation from baseline to 4 weeks of treatment. [units: Days per week with symptoms] Mean (Standard Deviation)	-2.95 (2.42)

No statistical analysis provided for Change in Frequency of days with Acid Regurgitation from baseline to 4 weeks of treatment.

6. Secondary Outcome Measure: Change in Frequency of days with Acid Regurgitation from baseline to 8 weeks of treatment. [ Time Frame: At Baseline and 8 weeks. ]

Measure Type	Secondary
Measure Name	Change in Frequency of days with Acid Regurgitation from baseline to 8 weeks of treatment.
Measure Description	Reported frequency of days with Acid regurgitation at week 8 - reported frequency of days with acid regurgitation at baseline. Four dimensions are defined for the Reflux Disease Questionnaire (RDQ) – heartburn, regurgitation, GORD dimension and dyspepsia: stomach. Scores for each dimension are range from 0 to 5 for frequency (not present to daily) and/or severity (not present to severe).
Time Frame	At Baseline and 8 weeks.
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.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Measured Values

	Esomeprazole 40mg, daily
Number of Participants Analyzed [units:participants]	311
Change in Frequency of days with Acid Regurgitation from baseline to 8 weeks of treatment. [units: Days per week with symptoms] Mean (Standard Deviation)	-3.28 (2.51)

No statistical analysis provided for Change in Frequency of days with Acid Regurgitation from baseline to 8 weeks of treatment.

7. Secondary Outcome Measure: Change in Frequency of Epigastric Pain after 4 weeks of treatment [ Time Frame: At Baseline and 4 weeks ]

Measure Type	Secondary
Measure Name	Change in Frequency of Epigastric Pain after 4 weeks of treatment
Measure Description	Reported frequency of days with Epigastric Pain at week 4 - reported frequency of days with Epigastric Pain at baseline. Four dimensions are defined for the Reflux Disease Questionnaire (RDQ) – heartburn, regurgitation, GORD dimension and dyspepsia: stomach. Scores for each dimension are range from 0 to 5 for frequency (not present to daily) and/or severity (not present to severe).
Time Frame	At Baseline and 4 weeks
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.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Measured Values

	Esomeprazole 40mg, daily
Number of Participants Analyzed [units:participants]	311
Change in Frequency of Epigastric Pain after 4 weeks of treatment [units: Days per week with pain] Mean (Standard Deviation)	-2.77 (2.5)

No statistical analysis provided for Change in Frequency of Epigastric Pain after 4 weeks of treatment

8. Secondary Outcome Measure: Change in Frequency of Epigastric Pain after 8 weeks of treatment [ Time Frame: At Baseline and 8 weeks ]

Measure Type	Secondary
Measure Name	Change in Frequency of Epigastric Pain after 8 weeks of treatment
Measure Description	Reported frequency of days with Epigastric Pain at week 8 - reported frequency of days with Epigastric Pain at baseline. Four dimensions are defined for the Reflux Disease Questionnaire (RDQ) – heartburn, regurgitation, GORD dimension and dyspepsia: stomach. Scores for each dimension were range from 0 to 5 for frequency (not present to daily) and severity (not present to severe).
Time Frame	At Baseline and 8 weeks
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.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Measured Values

	Esomeprazole 40mg, daily
Number of Participants Analyzed [units:participants]	311
Change in Frequency of Epigastric Pain after 8 weeks of treatment [units: Days per week with pain] Mean (Standard Deviation)	-3.16 (2.52)

No statistical analysis provided for Change in Frequency of Epigastric Pain after 8 weeks of treatment

9. Secondary Outcome Measure: Change in Severity of Epigastric Pain after 8 weeks of treatment [ Time Frame: At Baseline and 8 weeks ]

Measure Type	Secondary
Measure Name	Change in Severity of Epigastric Pain after 8 weeks of treatment
Measure Description	Reported severity of epigastric pain at week 8 on RDQ - reported severity of epigastric pain at baseline on RDQ (RDQ: Reflux Disease Questionnaire - by AstraZeneca LLP, 2000, values from "None" to "Severe". Four dimensions are defined for the RDQ – heartburn, regurgitation, GORD dimension and dyspepsia: stomach. Scores for each dimension are range from 0 to 5 for frequency (not present to daily) and/or severity (not present to severe).
Time Frame	At Baseline and 8 weeks
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.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Measured Values

	Esomeprazole 40mg, daily
Number of Participants Analyzed [units:participants]	311
Change in Severity of Epigastric Pain after 8 weeks of treatment [units: Units of scale] Mean (Standard Deviation)	-1.34 (1.1)

No statistical analysis provided for Change in Severity of Epigastric Pain after 8 weeks of treatment

10. Secondary Outcome Measure: Change in Severity of Epigastric Pain after 4 weeks of treatment [ Time Frame: At Baseline and 4 weeks ]

Measure Type	Secondary
Measure Name	Change in Severity of Epigastric Pain after 4 weeks of treatment
Measure Description	Reported severity of epigastric pain at week 4 on RDQ - reported severity of epigastric pain at baseline on RDQ (RDQ: Reflux Disease Questionnaire - by AstraZeneca LLP, 2000, values from "None" to "Severe". Four dimensions are defined for the RDQ – heartburn, regurgitation, GORD dimension and dyspepsia: stomach. Scores for each dimension are range from 0 to 5 for frequency (not present to daily) and/or severity (not present to severe).
Time Frame	At Baseline and 4 weeks
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.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Measured Values

	Esomeprazole 40mg, daily
Number of Participants Analyzed [units:participants]	311
Change in Severity of Epigastric Pain after 4 weeks of treatment [units: Units of scale] Mean (Standard Deviation)	-1.17 (1.1)

No statistical analysis provided for Change in Severity of Epigastric Pain after 4 weeks of treatment

11. Secondary Outcome Measure: Change in Severity of Acid Regurgitation after 8 weeks of treatment [ Time Frame: At Baseline and 8 weeks ]

Measure Type	Secondary
Measure Name	Change in Severity of Acid Regurgitation after 8 weeks of treatment
Measure Description	Reported severity of acid regurgitation at week 8 on RDQ - reported severity of acid regurgitation at baseline on RDQ (RDQ: Reflux Disease Questionnaire - by AstraZeneca LLP, 2000, values from "None" to "Severe". Four dimensions are defined for the RDQ – heartburn, regurgitation, GORD dimension and dyspepsia: stomach. Scores for each dimension are range from 0 to 5 for frequency (not present to daily) and/or severity (not present to severe).
Time Frame	At Baseline and 8 weeks
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.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Measured Values

	Esomeprazole 40mg, daily
Number of Participants Analyzed [units:participants]	311
Change in Severity of Acid Regurgitation after 8 weeks of treatment [units: Units of scale] Mean (Standard Deviation)	-1.51 (1.09)

No statistical analysis provided for Change in Severity of Acid Regurgitation after 8 weeks of treatment

12. Secondary Outcome Measure: Change in Severity of Acid Regurgitation after 4 weeks of treatment [ Time Frame: At Baseline and 4 weeks ]

Measure Type	Secondary
Measure Name	Change in Severity of Acid Regurgitation after 4 weeks of treatment
Measure Description	Reported severity of acid regurgitation at week 4 on RDQ - reported severity of acid regurgitation at baseline on RDQ (RDQ: Reflux Disease Questionnaire - by AstraZeneca LLP, 2000, values from "None" to "Severe". Four dimensions are defined for the RDQ – heartburn, regurgitation, GORD dimension and dyspepsia: stomach. Scores for each dimension are range from 0 to 5 for frequency (not present to daily) and/or severity (not present to severe).
Time Frame	At Baseline and 4 weeks
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.

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Measured Values

	Esomeprazole 40mg, daily
Number of Participants Analyzed [units:participants]	311
Change in Severity of Acid Regurgitation after 4 weeks of treatment [units: Units of scale] Mean (Standard Deviation)	-1.31 (1.06)

No statistical analysis provided for Change in Severity of Acid Regurgitation after 4 weeks of treatment

Serious Adverse Events

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

Reporting Groups

	Description
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Serious Adverse Events

Esomeprazole 40mg, daily

Total, serious adverse events

# participants affected / at risk

4/317 (1.26%)

Cardiac disorders

Dizziness / Hypotension / Tachycardia¹,^†

# participants affected / at risk

1/317 (0.32%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastric Cancer¹,^†

# participants affected / at risk

1/317 (0.32%)

Reproductive system and breast disorders

Vaginal haemorrhage¹,^†

# participants affected / at risk

1/317 (0.32%)

Reproductive system and breast disorders

Uterine Leiomyoma¹,^†

# participants affected / at risk

1/317 (0.32%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.0
2	Term from vocabulary,

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
Esomeprazole 40mg, daily	Open-label daily esomeprazole 40 mg, daily for 8 weeks

Other Adverse Events

Esomeprazole 40mg, daily

Total, other (not including serious) adverse events

# participants affected / at risk

16/317 (5.05%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

16/317 (5.05%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.0
2	Term from vocabulary,

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:

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:	[email protected]