Investigate the effect of different doses of lesogaberan (AZD3355) as add-on to PPI in GERD patients with partial response to PPI

Study identifier:D9120C00019

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

Medical condition

Gastroesophageal Reflux Disease, Acid Reflux

Phase

Phase 2

Healthy volunteers

Study drug

lesogaberan (AZD3355), Placebo

Sex

All

Actual Enrollment

661

Study type

Interventional

Age

18 Years - 70 Years

Date

Study Start Date: 01 Oct 2009

Primary Completion Date: 01 Jul 2010

Study Completion Date: 01 Jul 2010

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2011 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Oklahoma City, OK, United States

Arms	Assigned Interventions
Experimental: 60 mg PPI+lesogaberan (AZD3355) 60 mg bid	Drug: lesogaberan (AZD3355) 60 mg, oral, capsules, bid for 4 w
Experimental: 120 mg PPI+lesogaberan (AZD3355) 120 mg bid	Drug: lesogaberan (AZD3355) 120 mg, oral, capsules, bid for 4 w
Experimental: 180 mg PPI+lesogaberan (AZD3355) 180 mg bid	Drug: lesogaberan (AZD3355) 180 mg, oral, capsules, bid for 4 w
Experimental: 240 mg PPI+lesogaberan (AZD3355) 240 mg bid	Drug: lesogaberan (AZD3355) 240 mg, oral, capsules, bid for 4 w
Placebo Comparator: Placebo PPI+ Placebo	Drug: Placebo oral,capsules, bid for 4 w

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

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 60 mg	PPI+AZD3355 60 mg twice daily (bid)
AZD3355 120 mg	PPI+AZD3355 120 mg twice daily (bid)
AZD3355 180 mg	PPI+AZD3355 180 mg twice daily (bid)
AZD3355 240 mg	PPI+AZD3355 240 mg twice daily (bid)
Placebo	PPI+Placebo

Participant Flow: Overall Study

	AZD3355 60 mg	AZD3355 120 mg	AZD3355 180 mg	AZD3355 240 mg	Placebo
STARTED	134	125	136	126	140
COMPLETED	121	109	114	114	122
NOT COMPLETED	13	16	22	12	18
Withdrawal by Subject	2	5	3	4	9
Eligibility criteria not fulfilled	4	0	4	1	0
Adverse Event	2	6	8	5	4
Protocol Violation	1	0	0	0	2
Developed study-specific withdrawal crit	2	0	3	0	1
Lost to Follow-up	1	4	2	0	0
Physician Decision	0	0	0	0	2
Patient moved	1	0	0	0	0
Wrong drug dispensed	0	1	0	0	0
Randomized in error	0	0	1	1	0
Lack of Efficacy	0	0	1	1	0

Baseline Characteristics

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

Reporting Groups

	Description
AZD3355 60 mg	PPI+AZD3355 60 mg twice daily (bid)
AZD3355 120 mg	PPI+AZD3355 120 mg twice daily (bid)
AZD3355 180 mg	PPI+AZD3355 180 mg twice daily (bid)
AZD3355 240 mg	PPI+AZD3355 240 mg twice daily (bid)
Placebo	PPI+Placebo

Baseline Measures

	AZD3355 60 mg	AZD3355 120 mg	AZD3355 180 mg	AZD3355 240 mg	Placebo	Total
Number of Participants [units: Participants]	134	125	136	126	140	661
Age Continuous [units: years] Mean ± Standard Deviation	47.4 ± 12.3	46.1 ± 13.5	48.0 ± 12.3	48.5 ± 12.1	48.3 ± 12.0	47.7 ± 12.4
Gender, Male/Female [units: Participants]
Female	84	75	75	75	67	376
Male	50	50	61	51	73	285

Outcome Measures

1. Primary Outcome Measure: Number of participants with a change in GERD symptoms corresponding to at least three more days of not more than mild symptoms on average per week during treatment (approximately 4 weeks) than during baseline (the 7 days before randomisation) [ Time Frame: The 7 days before randomisation (baseline) and during 26-30 days of treatment ]

Measure Type	Primary
Measure Name	Number of participants with a change in GERD symptoms corresponding to at least three more days of not more than mild symptoms on average per week during treatment (approximately 4 weeks) than during baseline (the 7 days before randomisation)
Measure Description	Symptom intensity rated by participants twice daily on a six-graded Likert scale (Did not have; Very mild; Mild; Moderate; Moderately severe; Severe) using an electronic Reflux Symptom Questionnaire diary. (GERD = Gastroesophageal Reflux Disease)
Time Frame	The 7 days before randomisation (baseline) and during 26-30 days of treatment
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
AZD3355 60 mg	PPI+AZD3355 60 mg twice daily (bid)
AZD3355 120 mg	PPI+AZD3355 120 mg twice daily (bid)
AZD3355 180 mg	PPI+AZD3355 180 mg twice daily (bid)
AZD3355 240 mg	PPI+AZD3355 240 mg twice daily (bid)
Placebo	PPI+Placebo

Measured Values

	AZD3355 60 mg	AZD3355 120 mg	AZD3355 180 mg	AZD3355 240 mg	Placebo
Number of Participants Analyzed [units:participants]	134	125	136	126	140
Number of participants with a change in GERD symptoms corresponding to at least three more days of not more than mild symptoms on average per week during treatment (approximately 4 weeks) than during baseline (the 7 days before randomisation) [units: Participants]	28	32	32	33	25

No statistical analysis provided for Number of participants with a change in GERD symptoms corresponding to at least three more days of not more than mild symptoms on average per week during treatment (approximately 4 weeks) than during baseline (the 7 days before randomisation)

2. Secondary Outcome Measure: Absolute change from baseline to treatment period in percent days with at most mild GERD symptoms. [ Time Frame: The 7 days before randomisation (baseline) and during 26-30 days of treatment ]

Measure Type	Secondary
Measure Name	Absolute change from baseline to treatment period in percent days with at most mild GERD symptoms.
Measure Description	Symptom intensity rated by participants twice daily on a six-graded Likert scale (Did not have; Very mild; Mild; Moderate; Moderately severe; Severe) using an electronic Reflux Symptom Questionnaire diary (GERD = Gastroesophageal Reflux Disease)
Time Frame	The 7 days before randomisation (baseline) and during 26-30 days of treatment
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
AZD3355 60 mg	PPI+AZD3355 60 mg twice daily (bid)
AZD3355 120 mg	PPI+AZD3355 120 mg twice daily (bid)
AZD3355 180 mg	PPI+AZD3355 180 mg twice daily (bid)
AZD3355 240 mg	PPI+AZD3355 240 mg twice daily (bid)
Placebo	PPI+Placebo

Measured Values

	AZD3355 60 mg	AZD3355 120 mg	AZD3355 180 mg	AZD3355 240 mg	Placebo
Number of Participants Analyzed [units:participants]	132	117	133	123	135
Absolute change from baseline to treatment period in percent days with at most mild GERD symptoms. [units: Percent] Median (Inter-Quartile Range)	10.7 (0 to 35.7)	17.2 (0 to 46.4)	11.9 (0 to 40.9)	12.5 (0 to 47.1)	0 (0 to 30.8)

No statistical analysis provided for Absolute change from baseline to treatment period in percent days with at most mild GERD symptoms.

Serious Adverse Events

Time Frame	No text entered.
Additional Description	As a consequence of the definition of the analysis set for efficacy analysis and safety analysis respectively, one patient was included in the 120 mg group for efficacy analyses and in the 60 mg group for safety analyses.

Reporting Groups

	Description
AZD3355 60 mg	PPI+AZD3355 60 mg twice daily (bid)
AZD3355 120 mg	PPI+AZD3355 120 mg twice daily (bid)
AZD3355 180 mg	PPI+AZD3355 180 mg twice daily (bid)
AZD3355 240 mg	PPI+AZD3355 240 mg twice daily (bid)
Placebo	PPI+Placebo

Serious Adverse Events

AZD3355 60 mg

AZD3355 120 mg

AZD3355 180 mg

AZD3355 240 mg

Placebo

Total, serious adverse events

# participants affected / at risk

0/---

1/---

General disorders

Non-Cardiac Chest Pain¹,^†

# participants affected / at risk

0/---

1/---

0/---

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

Metastatic Gastric Cancer¹,^†

# participants affected / at risk

0/---

1/---

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	As a consequence of the definition of the analysis set for efficacy analysis and safety analysis respectively, one patient was included in the 120 mg group for efficacy analyses and in the 60 mg group for safety analyses.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
AZD3355 60 mg	PPI+AZD3355 60 mg twice daily (bid)
AZD3355 120 mg	PPI+AZD3355 120 mg twice daily (bid)
AZD3355 180 mg	PPI+AZD3355 180 mg twice daily (bid)
AZD3355 240 mg	PPI+AZD3355 240 mg twice daily (bid)
Placebo	PPI+Placebo

Other Adverse Events

AZD3355 60 mg

AZD3355 120 mg

AZD3355 180 mg

AZD3355 240 mg

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

13/---

12/---

16/---

20/---

9/---

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

5/---

7/---

6/---

10/---

1/---

Nervous system disorders

Paraesthesia¹

# participants affected / at risk

8/---

5/---

10/---

11/---

8/---

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0
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: 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:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=428&filename=CSP-D9120C00019.pdf
Download
CSR-D9120C00019.pdf
Download
CSP-D9120C00019.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Investigators

Principal Investigator

Debra Silberg

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=428&filename=CSP-D9120C00019.pdf

CSR-D9120C00019.pdf

CSP-D9120C00019.pdf

Trial Results Summaries