Double-blind Comparative Study of E3810 Tablets (10 or 20 mg b.i.d.) to Evaluate Efficacy and Safety in Patients With Refractory Reflux Esophagitis

• Sponsor: Eisai Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00770913
• Collaborator: (none)
• Enrollment: 337
• Locations: 54
• Arms: 3
• Duration (Months): 17
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of E3810 tablets in patients with Proton Pump Inhibitor-resistant reflux esophagitis.

Condition or Disease	Intervention/Treatment	Phase
Refractory Reflux Esophagitis	Drug: E3810; Drug: E3810; Drug: E3810	Phase 2/Phase 3

Detailed Description

This is a multicenter, randomized, double-blinded study. The efficacy with E3810 20 mg once daily is compared with E3810 20 mg twice daily and 10 mg twice daily using endoscopic recovery. The frequency of adverse event, etc., will be compared among 3 groups for safety assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 337 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Double-blind Comparative Study of E3810 Tablets (10 or 20 mg b.i.d.) to Evaluate Efficacy and Safety in Patients With Refractory Reflux Esophagitis
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1	Drug: E3810; 20 mg taken orally, once a day for 8 weeks.; Other Names: Aciphex
Experimental: 2	Drug: E3810; 10 mg, taken orally, twice a day for 8 weeks.; Other Names: Aciphex
Experimental: 3	Drug: E3810; 20 mg taken orally, twice a day for 8 weeks.; Other Names: Aciphex

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Healing Demonstrated Via Upper Gastrointestinal Endoscopy (Modified Los Angeles Classification: Grade N) [8 weeks]

   Grade N indicates a normal appearance of lower esophageal mucosa

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who have mucosal breaks (erosions, ulcers) on endoscopy and are diagnosed with reflux esophagitis.

• Proton Pump Inhibitor standard dose-resistant reflux esophagitis.

• Patients who are 20 years and older when informed consent is obtained.

Exclusion Criteria:

• Patients with a concurrent severe illness, serious heart disease, comorbid severe disease such as hematology, kidney disease, or liver disease.

• Patients with malignancy.

• Patients who are taking another trial drug or the interval between the end of treatment and screening is less than 12 weeks.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Nagakute	Aichi	Japan
2		Nagoya	Aichi	Japan
3		Abiko	Chiba	Japan
4		Kashiwa	Chiba	Japan
5		Yachiyo	Chiba	Japan
6		Chikushino	Fukuoka	Japan
7		Omuta	Fukuoka	Japan
8		Tagawa	Fukuoka	Japan
9		Koriyama	Fukushima	Japan
10		Hashima	Gifu	Japan
11		Maebashi	Gunma	Japan
12		Asahikawa	Hokkaido	Japan
13		Sapporo	Hokkaido	Japan
14		Itami	Hyogo	Japan
15		Nishinomiya	Hyogo	Japan
16		Hitachi	Ibaraki	Japan
17		Takamatsu	Kagawa	Japan
18		Kirishima	Kagoshima	Japan
19		Kawasaki	Kanagawa	Japan
20		Yokohama	Kanagawa	Japan
21		Ishinomaki	Miyagi	Japan
22		Yamatokoriyama	Nara	Japan
23		Beppu	Oita	Japan
24		Hirakata	Osaka	Japan
25		Karatsu	Saga	Japan
26		Kusatsu	Shiga	Japan
27		Izumo	Shimane	Japan
28		Matsue	Shimane	Japan
29		Fujieda	Shizuoka	Japan
30		Hamamatsu	Shizuoka	Japan
31		Shimada	Shizuoka	Japan
32		Ohtawara	Tochigi	Japan
33		Bunkyo	Tokyo	Japan
34		Itabashi	Tokyo	Japan
35		Setagaya	Tokyo	Japan
36		Shinagawa	Tokyo	Japan
37		Shinjuku	Tokyo	Japan
38		Hofu	Yamaguchi	Japan
39		Shimonoseki	Yamaguchi	Japan
40		Akita		Japan
41		Fukuoka		Japan
42		Gifu		Japan
43		Hiroshima		Japan
44		Kagoshima		Japan
45		Kouchi		Japan
46		Kumamoto		Japan
47		Kyoto		Japan
48		Nagasaki		Japan
49		Oita		Japan
50		Okayama		Japan
51		Osaka		Japan
52		Saga		Japan
53		Shizuoka		Japan
54		Yamagata		Japan

Sponsors and Collaborators

• Eisai Co., Ltd.

Investigators

• Study Director: Tomoki Kubota, New Product Development Dept., Clinical Research Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eisai Co., Ltd.
• ClinicalTrials.gov Identifier: NCT00770913
• Other Study ID Numbers: E3810-J081-304
• First Posted: Oct 10, 2008
• Last Update Posted: Apr 18, 2012
• Last Verified: Jun 1, 2010

• Keywords provided by Eisai Co., Ltd.: reflux esophagitis; rabeprazole; GERD; Japan
• Additional relevant MeSH terms: Gastroesophageal Reflux; Esophagitis; Esophagitis, Peptic; Rabeprazole

Study Results

Participant Flow

Recruitment Details	This study was recruited at 71 centers in Japan during the period of 17-Oct-2008 to 12-Nov-2009.
Pre-assignment Detail	There was no run-in phase before assignment to E3810 treatment groups in this study.

Arm/Group Title	E3810 20 mg Once Daily	E3810 10 mg Twice Daily	E3810 20 mg Twice Daily
Arm/Group Description	E3810 20mg once daily orally for 8 weeks	E3810 10mg twice daily orally for 8 weeks	E3810 20mg twice daily orally for 8 weeks
Period Title: Overall Study
STARTED	113	111	113
COMPLETED	102	103	100
NOT COMPLETED	11	8	13

Baseline Characteristics

Arm/Group Title	E3810 20 mg Once Daily	E3810 10 mg Twice Daily	E3810 20 mg Twice Daily	Total
Arm/Group Description	E3810 20mg once daily orally for 8 weeks	E3810 10mg twice daily orally for 8 weeks	E3810 20mg twice daily orally for 8 weeks	Total of all reporting groups
Overall Participants	110	111	111	332
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.5 (13.9)	65.5 (13.3)	66.6 (13.8)	65.5 (13.6)
Sex: Female, Male (Count of Participants)
Female	53 48.2%	59 53.2%	62 55.9%	174 52.4%
Male	57 51.8%	52 46.8%	49 44.1%	158 47.6%
Race/Ethnicity, Customized (participants) [Number]
Asian	110 100%	111 100%	111 100%	332 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Healing Demonstrated Via Upper Gastrointestinal Endoscopy (Modified Los Angeles Classification: Grade N)
Description	Grade N indicates a normal appearance of lower esophageal mucosa
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

The primary analysis was on the full analysis set (FAS) population.

Arm/Group Title	E3810 20 mg Once Daily	E3810 10 mg Twice Daily	E3810 20 mg
Arm/Group Description	E3810 20 mg once daily orally for 8 weeks	E3810 10 mg twice daily orally for 8 weeks	E3810 20 mg twice daily orally for 8 weeks
Measure Participants	113	111	113
Number [Percentage of Participants]	58.8 53.5%	78.4 70.6%	77.0 69.4%

Adverse Events

Adverse Event Reporting Description	The safety population includes all participants who took at least one dose of the assigned intervention. No.of Participants Analyzed: 113, 111, 113.Participants affected/at risk: 112, 111, 114. The drug was incorrectly prescribed. It should have been 20mg twice daily, but 20mg once daily was mistakenly prescribed despite of correct allocation.
Arm/Group Title	E3810 20 mg Once Daily		E3810 10 mg Twice Daily		E3810 20 mg
Arm/Group Description	E3810 20 mg once daily orally for 8 weeks		E3810 10 mg twice daily orally for 8 weeks		E3810 20 mg twice daily orally for 8 weeks
All Cause Mortality
	E3810 20 mg Once Daily		E3810 10 mg Twice Daily		E3810 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	E3810 20 mg Once Daily		E3810 10 mg Twice Daily		E3810 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/112 (2.7%)		6/111 (5.4%)		5/114 (4.4%)
Cardiac disorders
Cardiac failure	0/112 (0%)		1/111 (0.9%)		0/114 (0%)
Coronary artery stenosis	0/112 (0%)		0/111 (0%)		1/114 (0.9%)
Infections and infestations
Cellulitis	0/112 (0%)		0/111 (0%)		1/114 (0.9%)
Gastroenteritis	0/112 (0%)		1/111 (0.9%)		1/114 (0.9%)
Injury, poisoning and procedural complications
Tendon rupture	0/112 (0%)		1/111 (0.9%)		0/114 (0%)
Metabolism and nutrition disorders
Dehydration	0/112 (0%)		0/111 (0%)		1/114 (0.9%)
Musculoskeletal and connective tissue disorders
Back pain	1/112 (0.9%)		0/111 (0%)		0/114 (0%)
Chondrocalcinosis pyrophosphate	0/112 (0%)		0/111 (0%)		1/114 (0.9%)
Nervous system disorders
Intracranial aneurysm	1/112 (0.9%)		0/111 (0%)		0/114 (0%)
Putamen haemorrhage	0/112 (0%)		1/111 (0.9%)		0/114 (0%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	0/112 (0%)		1/111 (0.9%)		0/114 (0%)
Pneumothorax	1/112 (0.9%)		0/111 (0%)		0/114 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	0/112 (0%)		1/111 (0.9%)		0/114 (0%)
Vascular disorders
Aortic aneurysm	0/112 (0%)		0/111 (0%)		1/114 (0.9%)
Other (Not Including Serious) Adverse Events
	E3810 20 mg Once Daily		E3810 10 mg Twice Daily		E3810 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/112 (24.1%)		25/111 (22.5%)		20/114 (17.5%)
Gastrointestinal disorders
Constipation	2/112 (1.8%)		3/111 (2.7%)		5/114 (4.4%)
Diarrhoea	2/112 (1.8%)		5/111 (4.5%)		1/114 (0.9%)
Infections and infestations
Nasopharyngitis	8/112 (7.1%)		7/111 (6.3%)		4/114 (3.5%)
Investigations
Alanine aminotransferase increased	3/112 (2.7%)		0/111 (0%)		0/114 (0%)
Blood thyroid stimulating hormone increased	3/112 (2.7%)		7/111 (6.3%)		7/114 (6.1%)
Blood triglycerides increased	5/112 (4.5%)		1/111 (0.9%)		1/114 (0.9%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	4/112 (3.6%)		2/111 (1.8%)		2/114 (1.8%)

Limitations/Caveats

In the Participant flow section, there is only one "Reason for Not Completed" per participant reported, even if there were multiple reasons.

More Information

Certain Agreements

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

There is NOT 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.