Investigate the Effect of Different Doses of Lesogaberan (AZD3355) as add-on to PPI in GERD Patients With Partial Response to PPI

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01005251
• Collaborator: (none)
• Enrollment: 661
• Location: 1
• Arms: 5
• Duration (Months): 9
• Patients Per Site Per Month: 73.7

Study Details

Study Description

Brief Summary

This study is being carried out to see whether AZD3355 is an effective treatment as an add-on to PPI therapy in patients with Gastroesophageal Reflux Disease (GERD) with a partial response to PPI and to compare this with Proton Pump Inhibitor (PPI) treatment alone. Another goal of the study is to examine which of the investigated doses of AZD3355 is optimal for treatment of these patients. This study will also measure levels of drug in the blood and see how well it is tolerated.

Condition or Disease	Intervention/Treatment	Phase
Gastroesophageal Reflux Disease; Heartburn; Regurgitation	Drug: lesogaberan (AZD3355); Drug: lesogaberan (AZD3355); Drug: lesogaberan (AZD3355); Drug: lesogaberan (AZD3355); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 661 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. 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) [The 7 days before randomisation (baseline) and during 26-30 days of treatment]

   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)

Secondary Outcome Measures

1. Absolute Change From Baseline to Treatment Period in Percent Days With at Most Mild GERD Symptoms. [The 7 days before randomisation (baseline) and during 26-30 days of treatment]

   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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures

• Have at least 6 months history of GERD

• Continuously treated during the last 4 weeks before enrolment with daily optimized unchanged PPI therapy for any GERD indication

Exclusion Criteria:

• Patients that have not experienced any GERD symptom improvement at all during PPI treatment

• Prior surgery of the upper gastrointestinal tract.

• Subject who have any of the following conditions or diseases: Heart disease, Angina, Seizure disorders such as epilepsy, Congestive Heart Failure (CHF), Liver disease such as Cirrhosis or Hepatitis, Kidney disease, Lung disease or lung cancer, Cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Oklahoma City	Oklahoma	United States

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Debra Silberg, MD, AstraZeneca
• Principal Investigator: Nicholas Shaheen, MD, MPH, UNC Hospitals, 4141Chapel Hill, NC 27599 USA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01005251
• Other Study ID Numbers: D9120C00019
• First Posted: Oct 30, 2009
• Last Update Posted: Apr 25, 2011
• Last Verified: Mar 1, 2011

• Keywords provided by , ,: GERD treatment; Acid and non-acid Reflux; Heartburn; Regurgitation; Add-on treatment to PPI
• Additional relevant MeSH terms: Gastroesophageal Reflux; Heartburn; Lesogaberan

Study Results

Participant Flow

Arm/Group Title	AZD3355 60 mg	AZD3355 120 mg	AZD3355 180 mg	AZD3355 240 mg	Placebo
Arm/Group Description	PPI+AZD3355 60 mg twice daily (bid)	PPI+AZD3355 120 mg twice daily (bid)	PPI+AZD3355 180 mg twice daily (bid)	PPI+AZD3355 240 mg twice daily (bid)	PPI+Placebo
Period Title: Overall Study
STARTED	134	125	136	126	140
COMPLETED	121	109	114	114	122
NOT COMPLETED	13	16	22	12	18

Baseline Characteristics

Arm/Group Title	AZD3355 60 mg	AZD3355 120 mg	AZD3355 180 mg	AZD3355 240 mg	Placebo	Total
Arm/Group Description	PPI+AZD3355 60 mg twice daily (bid)	PPI+AZD3355 120 mg twice daily (bid)	PPI+AZD3355 180 mg twice daily (bid)	PPI+AZD3355 240 mg twice daily (bid)	PPI+Placebo	Total of all reporting groups
Overall Participants	134	125	136	126	140	661
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.4 (12.3)	46.1 (13.5)	48.0 (12.3)	48.5 (12.1)	48.3 (12.0)	47.7 (12.4)
Sex: Female, Male (Count of Participants)
Female	84 62.7%	75 60%	75 55.1%	75 59.5%	67 47.9%	376 56.9%
Male	50 37.3%	50 40%	61 44.9%	51 40.5%	73 52.1%	285 43.1%

Outcome Measures

1. Primary Outcome

Title	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)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD3355 60 mg	AZD3355 120 mg	AZD3355 180 mg	AZD3355 240 mg	Placebo
Arm/Group Description	PPI+AZD3355 60 mg twice daily (bid)	PPI+AZD3355 120 mg twice daily (bid)	PPI+AZD3355 180 mg twice daily (bid)	PPI+AZD3355 240 mg twice daily (bid)	PPI+Placebo
Measure Participants	134	125	136	126	140
Number [Participants]	28 20.9%	32 25.6%	32 23.5%	33 26.2%	25 17.9%

2. Secondary Outcome

Title	Absolute Change From Baseline to Treatment Period in Percent Days With at Most Mild GERD Symptoms.
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD3355 60 mg	AZD3355 120 mg	AZD3355 180 mg	AZD3355 240 mg	Placebo
Arm/Group Description	PPI+AZD3355 60 mg twice daily (bid)	PPI+AZD3355 120 mg twice daily (bid)	PPI+AZD3355 180 mg twice daily (bid)	PPI+AZD3355 240 mg twice daily (bid)	PPI+Placebo
Measure Participants	132	117	133	123	135
Median (Inter-Quartile Range) [Percent]	10.7	17.2	11.9	12.5	0

Adverse Events

Adverse Event Reporting 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.
Arm/Group Title	AZD3355 60 mg		AZD3355 120 mg		AZD3355 180 mg		AZD3355 240 mg		Placebo
Arm/Group Description	PPI+AZD3355 60 mg twice daily (bid)		PPI+AZD3355 120 mg twice daily (bid)		PPI+AZD3355 180 mg twice daily (bid)		PPI+AZD3355 240 mg twice daily (bid)		PPI+Placebo
All Cause Mortality
	AZD3355 60 mg		AZD3355 120 mg		AZD3355 180 mg		AZD3355 240 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	AZD3355 60 mg		AZD3355 120 mg		AZD3355 180 mg		AZD3355 240 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/ (NaN)		0/ (NaN)		0/ (NaN)		1/ (NaN)		1/ (NaN)
General disorders
Non-Cardiac Chest Pain	0/135 (0%)		0/124 (0%)		0/136 (0%)		1/126 (0.8%)		0/140 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic Gastric Cancer	0/135 (0%)		0/124 (0%)		0/136 (0%)		0/126 (0%)		1/140 (0.7%)
Other (Not Including Serious) Adverse Events
	AZD3355 60 mg		AZD3355 120 mg		AZD3355 180 mg		AZD3355 240 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/ (NaN)		12/ (NaN)		16/ (NaN)		20/ (NaN)		9/ (NaN)
Gastrointestinal disorders
Diarrhoea	5/135 (3.7%)		7/124 (5.6%)		6/136 (4.4%)		10/126 (7.9%)		1/140 (0.7%)
Nervous system disorders
Paraesthesia	8/135 (5.9%)		5/124 (4%)		10/136 (7.4%)		11/126 (8.7%)		8/140 (5.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.