Efficacy and Safety of Dexlansoprazole Modified Release Formulation to Treat Heartburn

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00251745
• Collaborator: (none)
• Enrollment: 908
• Locations: 95
• Arms: 3
• Duration (Months): 5
• Patients Per Site: 9.6
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy and safety of daily treatment with Dexlansoprazole modified release (MR) (60 mg or 90 mg once daily [QD]) compared to placebo QD in relief of daytime and nighttime heartburn over 4 weeks in subjects with gastroesophageal reflux disease (GERD).

Condition or Disease	Intervention/Treatment	Phase
Gastroesophageal Reflux Disease	Drug: Dexlansoprazole MR; Drug: Dexlansoprazole MR; Drug: Placebo	Phase 3

Detailed Description

This is a Phase 3, randomized, double-blind, multicenter, placebo-controlled, 3-arm study with a 4 week treatment period. This study will compare the efficacy of daily Dexlansoprazole MR (60 mg and 90 mg) with that of placebo when administered orally as a single daily dose in the morning, before breakfast. The study is designed to evaluate symptom relief in subjects with symptomatic non-erosive GERD. Approximately 450 subjects will be enrolled at approximately 120 U.S. and potentially ex U.S. sites. The study consists of two periods; a screening period, which will last a minimum of 7 days and a maximum of 21 days, and a treatment period, which will last 4 weeks.

Because the development plan for Dexlansoprazole MR was revised, the results of 2 identical studies, T-GD04-082 (this posting, NCT00241745) and T-GD04-083 (NCT00251758), were combined and analyzed as a single larger study referred to as study T-GD04-082. A total of 908 subjects were included in the combined analysis; 416 subjects were enrolled into Study T-GD04-082 and 492 subjects were enrolled into Study T-GD04-083.

Study Design

• Study Type: Interventional
• Actual Enrollment: 908 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study to Evaluate the Efficacy and Safety of Dexlansoprazole MR (60 mg Once-Daily (QD) and 90 mg QD) Compared to Placebo on Symptom Relief in Subjects With Symptomatic Non-Erosive Gastroesophageal Reflux Disease (GERD)
• Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: May 1, 2006
• Actual Study Completion Date: May 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexlansoprazole MR 60 mg QD	Drug: Dexlansoprazole MR; Dexlansoprazole MR 60 mg, capsules, orally, once daily for 4 weeks.; Other Names: TAK-390MR Kapidex Dexilant
Experimental: Dexlansoprazole MR 90 mg QD	Drug: Dexlansoprazole MR; Dexlansoprazole MR 90 mg, capsules, orally, once daily for 4 weeks.; Other Names: TAK-390MR Kapidex Dexilant
Placebo Comparator: Placebo	Drug: Placebo; Dexlansoprazole placebo-matching capsules, orally, once daily for 4 weeks.

Outcome Measures

Primary Outcome Measures

1. Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median [4 weeks]

   The percentage was calculated as the days that were heartburn-free out of the total number of days for which either a daytime or nighttime result was marked.

2. Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean [4 weeks]

   The percentage was calculated as the days that were heartburn-free out of the total number of days for which either a daytime or nighttime result was marked.

Secondary Outcome Measures

1. Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median [4 weeks]

   The percentage was calculated as the nights that were heartburn-free out of the total number of days for which a nighttime result was marked.

2. Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean [4 weeks]

   The percentage was calculated as the nights that were heartburn-free out of the total number of days for which a nighttime result was marked.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects with Non-Erosive Gastroesophageal Reflux Disease identifying their main symptom as heartburn.

• History of episodes of heartburn for 6 months or longer prior to screening.

• History of episodes of heartburn for 4 or more days during the 7 days prior to Day -1 as recorded in the electronic diary.

Exclusion Criteria:

• Use of prescription or non-prescription proton pump inhibitors (PPIs), histamine (H2) receptor antagonists, sucralfate, misoprostol or prokinetics throughout the study·

• Use of antacids (except for study supplied Gelusil®).

• Use of drugs with significant anticholinergic effects.

• Need for continuous anticoagulant (blood thinner) therapy.

• Endoscopic Barrett's esophagus and/or definite dysplastic changes in the esophagus.

• History of dilatation of esophageal strictures, other than a Schatzki's ring (a ring of mucosal tissue near the lower esophageal sphincter).

• Current or historical evidence of Zollinger-Ellison syndrome or other hypersecretory condition.

• History of gastric, duodenal or esophageal surgery except simple oversew of an ulcer.

• Acute upper gastrointestinal (UGI) hemorrhage within 4 weeks of the screening endoscopy.

• Erosive Esophagitis seen on endoscopy during study screening.

• Co-existing diseases affecting the esophagus.

• Abnormal laboratory values that suggest significant clinical disease.

• Known acquired immunodeficiency syndrome (AIDS)

• Females pregnant or lactating.

• History of Alcohol abuse.

• History of Cancer within 3 years prior to screening.

• Chronic (>12 doses per month) use of nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclo-oxygenase-2 (COX-2) inhibitors

• Subjects who, in the opinion of the investigator, are unable to comply with the requirements of the study or are unsuitable for any reason.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Alabaster	Alabama	United States
2		Birmingham	Alabama	United States
3		Huntsville	Alabama	United States
4		Scottsdale	Arizona	United States
5		Tucson	Arizona	United States
6		Anaheim	California	United States
7		Chula Vista	California	United States
8		Fullerton	California	United States
9		Garden Grove	California	United States
10		Irvine	California	United States
11		Lancaster	California	United States
12		Long Beach	California	United States
13		Los Angeles	California	United States
14		Mission Hills	California	United States
15		Palm Springs	California	United States
16		Redwood City	California	United States
17		San Diego	California	United States
18		San Luis Obispo	California	United States
19		San Marino	California	United States
20		Boulder	Colorado	United States
21		Colorado Springs	Colorado	United States
22		Lone Tree	Colorado	United States
23		Wheat Ridge	Colorado	United States
24		Waterbury	Connecticut	United States
25		Boynton Beach	Florida	United States
26		Jacksonsville	Florida	United States
27		Jupiter	Florida	United States
28		Kissimmee	Florida	United States
29		Lakeland	Florida	United States
30		New Port Richey	Florida	United States
31		Atlanta	Georgia	United States
32		Honolulu	Hawaii	United States
33		Arlington Heights	Illinois	United States
34		Chicago	Illinois	United States
35		Hines	Illinois	United States
36		Oak Park	Illinois	United States
37		Rockford	Illinois	United States
38		Clive	Iowa	United States
39		Dubuque	Iowa	United States
40		Newton	Kansas	United States
41		Shawnee Mission	Kansas	United States
42		Topeka	Kansas	United States
43		Metairie	Louisiana	United States
44		Shreveport	Louisiana	United States
45		Hollywood	Maryland	United States
46		Lutherville	Maryland	United States
47		Troy	Michigan	United States
48		Chaska	Minnesota	United States
49		Jackson	Mississippi	United States
50		Mexico	Missouri	United States
51		Saint Louis	Missouri	United States
52		Washington	Missouri	United States
53		Omaha	Nebraska	United States
54		Pahrump	Nevada	United States
55		New Brunswick	New Jersey	United States
56		Binghamton	New York	United States
57		Brooklyn	New York	United States
58		Great Neck	New York	United States
59		Rochester	New York	United States
60		Charlotte	North Carolina	United States
61		Elkin	North Carolina	United States
62		Greensboro	North Carolina	United States
63		Hickory	North Carolina	United States
64		Salisbury	North Carolina	United States
65		Statesville	North Carolina	United States
66		Winston Salem	North Carolina	United States
67		Cincinnati	Ohio	United States
68		Mayfield Heights	Ohio	United States
69		Warren	Ohio	United States
70		Oklahoma City	Oklahoma	United States
71		Portland	Oregon	United States
72		Beaver Falls	Pennsylvania	United States
73		Duncansville	Pennsylvania	United States
74		Lansdale	Pennsylvania	United States
75		Bristol	Tennessee	United States
76		Chattanooga	Tennessee	United States
77		Hermitage	Tennessee	United States
78		Nashville	Tennessee	United States
79		Austin	Texas	United States
80		Beaumont	Texas	United States
81		Bryan	Texas	United States
82		Corsicana	Texas	United States
83		El Paso	Texas	United States
84		Fort Worth	Texas	United States
85		Houston	Texas	United States
86		San Antonio	Texas	United States
87		Bountiful	Utah	United States
88		Ogden	Utah	United States
89		Salt Lake City	Utah	United States
90		West Jordan	Utah	United States
91		Chesapeake	Virginia	United States
92		Danville	Virginia	United States
93		Spokane	Washington	United States
94		Milwaukee	Wisconsin	United States
95		Monroe	Wisconsin	United States

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• For the Dexilant Package Insert refer to this link

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00251745
• Other Study ID Numbers: T-GD04-082; U1111-1114-0144
• First Posted: Nov 10, 2005
• Last Update Posted: Apr 28, 2011
• Last Verified: Apr 1, 2011

• Keywords provided by , ,: Non-Erosive Gastroesophageal Reflux Disease (GERD); Heartburn
• Additional relevant MeSH terms: Gastroesophageal Reflux; Esophagitis, Peptic; Dexlansoprazole; Lansoprazole

Study Results

Participant Flow

Recruitment Details	Subjects enrolled at 157 sites in the United States (75 in Study T-GD04-082 [this posting, NCT00251745] and 82 in Study T-GD04-083 [NCT00251758]; date of first dose: 07 December 2005; date of last procedure: 23 May 2006).
Pre-assignment Detail	Subjects with endoscopically documented normal esophageal mucosa were enrolled in Dexlansoprazole Modified Release (MR) or Placebo once daily (QD) treatment group; subjects were instructed that lifestyle or behavioral modifications designed to treat their symptoms of Gastroesophageal Reflux Disease (GERD) should not be altered throughout the study.

Arm/Group Title	Placebo QD	Dexlansoprazole MR 60 mg QD	Dexlansoprazole MR 90 mg QD
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 4 weeks.
Period Title: Overall Study
STARTED	292	312	304
COMPLETED	264	285	277
NOT COMPLETED	28	27	27

Baseline Characteristics

Arm/Group Title	Placebo QD	Dexlansoprazole MR 60 mg QD	Dexlansoprazole MR 90 mg QD	Total
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 4 weeks.	Total of all reporting groups
Overall Participants	292	312	304	908
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.0 (13.60)	48.0 (13.55)	46.7 (13.64)	47.9 (13.61)
Age, Customized (participants) [Number]
<45 years	107 36.6%	125 40.1%	135 44.4%	367 40.4%
45 - <65 years	146 50%	155 49.7%	139 45.7%	440 48.5%
≥65 years	39 13.4%	32 10.3%	30 9.9%	101 11.1%
Sex: Female, Male (Count of Participants)
Female	216 74%	214 68.6%	213 70.1%	643 70.8%
Male	76 26%	98 31.4%	91 29.9%	265 29.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 1%	3 1%	8 2.6%	14 1.5%
Asian	9 3.1%	12 3.8%	7 2.3%	28 3.1%
Native Hawaiian or Other Pacific Islander	1 0.3%	3 1%	0 0%	4 0.4%
Black or African American	34 11.6%	46 14.7%	41 13.5%	121 13.3%
White	240 82.2%	246 78.8%	245 80.6%	731 80.5%
More than one race	5 1.7%	1 0.3%	3 1%	9 1%
Unknown or Not Reported	0 0%	1 0.3%	0 0%	1 0.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	60 20.5%	58 18.6%	61 20.1%	179 19.7%
Not Hispanic or Latino	232 79.5%	254 81.4%	243 79.9%	729 80.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median
Description	The percentage was calculated as the days that were heartburn-free out of the total number of days for which either a daytime or nighttime result was marked.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Analysis was conducted on an intent-to-treat (ITT) population that included all randomized subjects who received at least 1 dose of study drug and completed at least 1 diary entry for heartburn during treatment. All ITT populations excluded subjects with confirmed Barrett's esophagus and/or definite dysplastic changes.

Arm/Group Title	Placebo QD	Dexlansoprazole MR 60 mg QD	Dexlansoprazole MR 90 mg QD
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 4 weeks.
Measure Participants	290	306	298
Median (Inter-Quartile Range) [percentage of days]	17.0	45.7	52.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo QD, Dexlansoprazole MR 60 mg QD
	Comments	The comparison between the two treatment groups was made using Wilcoxon rank-sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.00001
	Comments	The overall 0.0025 level of significance for the multiple comparisons of each dexlansoprazole MR dose to placebo was controlled using Hochberg's method.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo QD, Dexlansoprazole MR 90 mg QD
	Comments	The comparison between the two treatment groups was made using Wilcoxon rank-sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.00001
	Comments	The overall 0.0025 level of significance for the multiple comparisons of each dexlansoprazole MR dose to placebo was controlled using Hochberg's method.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole MR 60 mg QD, Dexlansoprazole MR 90 mg QD
	Comments	The comparison between the two treatment groups was made using Wilcoxon rank-sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.15505
	Comments	Statistical significance was determined at 0.0025 level without adjustment for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean
Description	The percentage was calculated as the days that were heartburn-free out of the total number of days for which either a daytime or nighttime result was marked.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Analysis was conducted on an intent-to-treat (ITT) population that included all randomized subjects who received at least 1 dose of study drug and completed at least 1 diary entry for heartburn during treatment. All ITT populations excluded subjects with confirmed Barrett's esophagus and/or definite dysplastic changes.

Arm/Group Title	Placebo QD	Dexlansoprazole MR 60 mg QD	Dexlansoprazole MR 90 mg QD
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 4 weeks.
Measure Participants	290	306	298
Mean (Standard Deviation) [percentage of days]	24.9 (25.7)	44.8 (33.8)	49.1 (34.2)

3. Secondary Outcome

Title	Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median
Description	The percentage was calculated as the nights that were heartburn-free out of the total number of days for which a nighttime result was marked.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Analysis was conducted on an ITT population (all randomized subjects who received at least 1 dose of study drug and completed at least 1 diary entry for heartburn during treatment), but excluded subjects without any morning diary entries on Day 1 or later.

Arm/Group Title	Placebo QD	Dexlansoprazole MR 60 mg QD	Dexlansoprazole MR 90 mg QD
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 4 weeks.
Measure Participants	290	306	298
Median (Inter-Quartile Range) [percentage of days]	51.0	72.3	76.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo QD, Dexlansoprazole MR 60 mg QD
	Comments	The comparison between the two treatment groups was made using Wilcoxon rank-sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.00001
	Comments	The overall 0.0025 level of significance for the multiple comparisons of each dexlansoprazole MR dose to placebo was controlled using Hochberg's method.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo QD, Dexlansoprazole MR 90 mg QD
	Comments	The comparison between the two treatment groups was made using Wilcoxon rank-sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.00001
	Comments	The overall 0.0025 level of significance for the multiple comparisons of each dexlansoprazole MR dose to placebo was controlled using Hochberg's method.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole MR 60 mg QD, Dexlansoprazole MR 90 mg QD
	Comments	The comparison between the two treatment groups was made using Wilcoxon rank-sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.38740
	Comments	Statistical significance was determined at 0.0025 level without adjustment for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean
Description	The percentage was calculated as the nights that were heartburn-free out of the total number of days for which a nighttime result was marked.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Analysis was conducted on an ITT population (all randomized subjects who received at least 1 dose of study drug and completed at least 1 diary entry for heartburn during treatment), but excluded subjects without any morning diary entries on Day 1 or later.

Arm/Group Title	Placebo QD	Dexlansoprazole MR 60 mg QD	Dexlansoprazole MR 90 mg QD
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 4 weeks.
Measure Participants	290	306	298
Mean (Standard Deviation) [percentage of days]	49.6 (34.1)	62.0 (34.5)	64.4 (34.6)

Adverse Events

Arm/Group Title	Placebo QD		Dexlansoprazole MR 60 mg QD		Dexlansoprazole MR 90 mg QD
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.		Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 4 weeks.		Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 4 weeks.
All Cause Mortality
	Placebo QD		Dexlansoprazole MR 60 mg QD		Dexlansoprazole MR 90 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo QD		Dexlansoprazole MR 60 mg QD		Dexlansoprazole MR 90 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/ (NaN)		2/ (NaN)		1/ (NaN)
Hepatobiliary disorders
Cholecystitis and Cholelithiasis	0/292 (0%)		0/312 (0%)		1/304 (0.3%)
Injury, poisoning and procedural complications
Non-site Specific Injuries Not Elsewhere Classified (NEC)	0/292 (0%)		1/312 (0.3%)		0/304 (0%)
Poisoning and Toxicity	0/292 (0%)		1/312 (0.3%)		0/304 (0%)
Other (Not Including Serious) Adverse Events
	Placebo QD		Dexlansoprazole MR 60 mg QD		Dexlansoprazole MR 90 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/ (NaN)		55/ (NaN)		54/ (NaN)
Gastrointestinal disorders
Diarrhoea (Excl Infective)	13/292 (4.5%)		15/312 (4.8%)		8/304 (2.6%)
Gastrointestinal and Abdominal Pains (Excl Oral and Throat)	12/292 (4.1%)		23/312 (7.4%)		15/304 (4.9%)
Nausea and Vomiting Symptoms	10/292 (3.4%)		15/312 (4.8%)		9/304 (3%)
Infections and infestations
Upper Respiratory Tract Infections	4/292 (1.4%)		11/312 (3.5%)		24/304 (7.9%)
Nervous system disorders
Headaches NEC	15/292 (5.1%)		13/312 (4.2%)		11/304 (3.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.