A Study of Dexlansoprazole Modified Release Formulation to Treat Night Heartburn

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00627016
• Collaborator: (none)
• Enrollment: 305
• Locations: 43
• Arms: 2
• Duration (Months): 12
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether Dexlansoprazole once daily (QD) is effective in treating patients with night heartburn.

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

Detailed Description

This 4 week study of Dexlansoprazole (TAK-390MR) will be conducted by approximately 50 investigators in the United States in patients suffering from night heartburn.

Study Design

• Study Type: Interventional
• Actual Enrollment: 305 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Multicenter, Randomized, Double-Blind, Parallel Group, Placebo Controlled Trial to Evaluate the Efficacy of TAK-390MR (30 mg QD) Compared to Placebo on Relief of Nocturnal Heartburn in Subjects With Symptomatic Gastroesophageal Reflux Disease (GERD)
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexlansoprazole 30 mg QD	Drug: Dexlansoprazole; 30 mg capsule, orally, once daily for 4 weeks; Other Names: TAK-390 T-168390 TAK-390MR Kapidex Dexilant
Placebo Comparator: Placebo	Drug: Placebo; 1 capsule, orally, once daily for 4 weeks

Outcome Measures

Primary Outcome Measures

1. Median Percentage of Nights Without Heartburn Over 4 Weeks as Assessed by Daily Diary. [4 Weeks]

   Percentage calculated by the number of heartburn-free nights out of the total number of nights during the treatment period with a diary entry indicating presence or absence of nighttime heartburn in subjects who had ≥1 diary entry indicating presence or absence of nighttime heartburn, as indicated by the subject's daily diary. Subjects indicate the presence (Yes/No) of nocturnal heartburn symptoms in a Daily Electronic Diary. Nights missing diary results were excluded from the numerator and denominator.

Secondary Outcome Measures

1. Percent of Subjects With Relief of Night Time Heartburn Over the Last 7 Days of Treatment as Assessed by Daily Diary. [Last 7 days of treatment]

   Relief of nighttime heartburn was defined as 6 of 7 nights with no heartburn and at most 1 night with mild heartburn; lack of relief of nighttime heartburn was defined as 2 or more out of 7 nights with heartburn, or 1 night with at least moderate heartburn. Subjects indicate the presence and severity (mild, moderate, severe, or very severe) of nocturnal heartburn in a Daily Electronic Diary. The percentage was calculated as the number of subjects with relief of nighttime heartburn divided by the number of subjects whose relief status could be determined.

2. Percentage of Participants With Relief of Gastro-Esophageal Reflux Disease (GERD) Associated Sleep Disturbances Over the Last 7 Days of Treatment as Assessed by Daily Diary. [Last 7 days of treatment]

   Relief of GERD-associated sleep disturbance was defined as 6 of 7 nights with no GERD associated sleep disturbances; lack of relief of GERD-associated sleep disturbance was defined as 2 or more out of 7 nights with GERD-associated sleep disturbance. Subjects indicate the presence (Yes/No) of GERD associated sleep disturbance in a Daily Electronic Diary. The percentage was calculated as the number of subjects with relief of GERD-associated sleep disturbance divided by the number of subjects whose relief status could be determined.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

• History of nocturnal heartburn and GERD associated sleep disturbances prior to screening.

• Meets both of the following criteria: 1) nocturnal heartburn severity of moderate, severe, or very severe on at least 3 of 7 nights and; 2) GERD related sleep disturbances on at least 3 of 7 nights.

• Subjects must have history of symptomatic GERD prior to screening with GERD symptoms that were responsive to acid-suppressive therapy.

Exclusion Criteria:

• Erosive esophagitis visualized during the screening endoscopy.

• Allergy to any proton pump inhibitor drug (lansoprazole, omeprazole, rabeprazole, pantoprazole, esomeprazole), any component of Dexlansoprazole, or Gelusil/antacid.

• Active gastric or duodenal ulcers within 30 days prior to randomization.

• Upper gastrointestinal bleeding within 6 months prior to randomization.

• Co-existing diseases affecting the esophagus (eg, eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal infection, and/or Barrett's esophagus).

• History of radiation therapy or cryotherapy to the esophagus, caustic or physiochemical trauma such as sclerotherapy to the esophagus.

• Subject requiring dilation for esophageal strictures and/or strictures preventing passage of the endoscope during the screening endoscopy. Schatzki's ring (a ring of mucosal tissue near the lower esophageal sphincter) is acceptable.

• Has another condition that could be the primary cause of the subject's sleep disturbance.

• Evidence of uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality (other than the disease being studied) which may impact the ability of the subject to participate or potentially confound the trial results.

• Diagnosis of cancer (except basal cell carcinoma) within 5 years of screening.

• Has a condition likely to require surgery during the study.

• Currently diagnosed with acquired immunodeficiency syndrome (AIDS).

• Abnormal clinical laboratory values.

• History of alcoholism or drug addiction.

• Subject who works the night shift.

• Subject who is planning to travel beyond 3 time zones during the study.

• Chronic use (more than 12 doses/month) of non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX 2) inhibitors within 30 days prior to randomization or anticipated use during the study.

• Use of the following medications during the 14 days prior to randomization or anticipated use during the study: proton pump inhibitors, sucralfate, misoprostol, corticosteroids, prokinetics, anticoagulant therapy, antiseizure medications (other than stable doses), psychotropic medications (other than stable doses), narcotic medications (occasional use allowed), bisphosphonates.

• Use of sleep medications, first generation antihistamines, benzodiazepines, modified cyclic antidepressants, antianxiety medications or drugs with significant anticholinergic effects such as tricyclic antidepressants or drugs with central nervous system effects that could mask perception of symptoms (eg, selective-serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors). However, subjects who remain on a stable regimen and dose of these medications during the 90 days prior to randomization and who agree to maintain the same regimen and dose during the trial will qualify. Also, short term use of anticholinergics for trial related procedures is not exclusionary. Second generation antihistamines are not excluded.

• Use of histamine (H2) receptor antagonists or antacids (except for trial supplied Gelusil) during the screening period or anticipated use during the treatment period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Tucson	Arizona	United States
2		Anaheim	California	United States
3		Garden Grove	California	United States
4		Lancaster	California	United States
5		Oakland	California	United States
6		San Diego	California	United States
7		Sherwood	California	United States
8		Westlake Village	California	United States
9		Jupiter	Florida	United States
10		Miami	Florida	United States
11		New Smyrna Beach	Florida	United States
12		Ocala	Florida	United States
13		Saint Petersburg	Florida	United States
14		Zephyrhills	Florida	United States
15		Moline	Illinois	United States
16		Clive	Iowa	United States
17		Wichita	Kansas	United States
18		Metairie	Louisiana	United States
19		Prince Frederick	Maryland	United States
20		Jefferson City	Missouri	United States
21		Egg Harbor Town	New Jersey	United States
22		Great Neck	New York	United States
23		Greensboro	North Carolina	United States
24		Harrisburg	North Carolina	United States
25		Winston-Salem	North Carolina	United States
26		Mogadore	Ohio	United States
27		Oklahoma City	Oklahoma	United States
28		Portland	Oregon	United States
29		Duncansville	Pennsylvania	United States
30		Bristol	Tennessee	United States
31		Chattanooga	Tennessee	United States
32		Johnson City	Tennessee	United States
33		Kingsport	Tennessee	United States
34		Nashville	Tennessee	United States
35		El Paso	Texas	United States
36		Fort Worth	Texas	United States
37		Houston	Texas	United States
38		Odessa	Texas	United States
39		San Antonio	Texas	United States
40		Ogden	Utah	United States
41		Norfolk	Virginia	United States
42		Spokane	Washington	United States
43		Monroe	Wisconsin	United States

Sponsors and Collaborators

• Takeda

Investigators

• Study Chair: Medical Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Dexilant Package Insert

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00627016
• Other Study ID Numbers: T-GD07-170; U1111-1113-9537
• First Posted: Feb 29, 2008
• Last Update Posted: Apr 28, 2011
• Last Verified: Apr 1, 2011

• Keywords provided by , ,: Non-Erosive Gastroesophageal Reflux Disease; GERD; heartburn; sleep disturbance; nocturnal Reflux
• Additional relevant MeSH terms: Gastroesophageal Reflux; Esophagitis, Peptic; Heartburn; Dexlansoprazole; Lansoprazole

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled at 33 investigative sites in the United States from 07 March 2008 to 20 March 2009.
Pre-assignment Detail	Subjects eligible for entry into the Treatment Period were randomized into one of two, once-daily (QD) treatment groups.

Arm/Group Title	Placebo	Dexlansoprazole 30 mg QD
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole 30 mg, capsules, orally, once daily for up to 4 weeks.
Period Title: Overall Study
STARTED	153	152
COMPLETED	147	146
NOT COMPLETED	6	6

Baseline Characteristics

Arm/Group Title	Placebo	Dexlansoprazole 30 mg QD	Total
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole 30 mg, capsules, orally, once daily for up to 4 weeks.	Total of all reporting groups
Overall Participants	153	152	305
Age, Customized (participants) [Number]
<45 years	75 49%	75 49.3%	150 49.2%
45 to <65 years	76 49.7%	75 49.3%	151 49.5%
>=65 years	2 1.3%	2 1.3%	4 1.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.9 (12.45)	44.6 (11.29)	44.2 (11.87)
Sex: Female, Male (Count of Participants)
Female	98 64.1%	97 63.8%	195 63.9%
Male	55 35.9%	55 36.2%	110 36.1%
Region of Enrollment (participants) [Number]
United States	153 100%	152 100%	305 100%
Number of Days with Night Heartburn (participants) [Number]
0-3 days	10 6.5%	3 2%	13 4.3%
4-5 days	36 23.5%	38 25%	74 24.3%
6-7 days	107 69.9%	111 73%	218 71.5%
Number of Nights with Sleep Disturbances Related to Gastroesophageal Reflux Disease (GERD) Symptoms (participants) [Number]
0-3 Nights	40 26.1%	33 21.7%	73 23.9%
4-5 Nights	53 34.6%	47 30.9%	100 32.8%
6-7 Nights	60 39.2%	72 47.4%	132 43.3%

Outcome Measures

1. Primary Outcome

Title	Median Percentage of Nights Without Heartburn Over 4 Weeks as Assessed by Daily Diary.
Description	Percentage calculated by the number of heartburn-free nights out of the total number of nights during the treatment period with a diary entry indicating presence or absence of nighttime heartburn in subjects who had ≥1 diary entry indicating presence or absence of nighttime heartburn, as indicated by the subject's daily diary. Subjects indicate the presence (Yes/No) of nocturnal heartburn symptoms in a Daily Electronic Diary. Nights missing diary results were excluded from the numerator and denominator.
Time Frame	4 Weeks

Outcome Measure Data

Analysis Population Description

Analysis was conducted on intent-to-treat subjects (randomized subjects who received at least 1 dose of study drug) who completed at least 1 diary entry for nighttime heartburn during treatment.

Arm/Group Title	Placebo	Dexlansoprazole 30 mg QD
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole 30 mg, capsules, orally, once daily for up to 4 weeks.
Measure Participants	153	151
Median (Inter-Quartile Range) [Percentage of nights]	35.7 (30.0)	73.1 (35.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dexlansoprazole 30 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance for the comparison of the primary endpoint was determined at 0.05 level.
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Percent of Subjects With Relief of Night Time Heartburn Over the Last 7 Days of Treatment as Assessed by Daily Diary.
Description	Relief of nighttime heartburn was defined as 6 of 7 nights with no heartburn and at most 1 night with mild heartburn; lack of relief of nighttime heartburn was defined as 2 or more out of 7 nights with heartburn, or 1 night with at least moderate heartburn. Subjects indicate the presence and severity (mild, moderate, severe, or very severe) of nocturnal heartburn in a Daily Electronic Diary. The percentage was calculated as the number of subjects with relief of nighttime heartburn divided by the number of subjects whose relief status could be determined.
Time Frame	Last 7 days of treatment

Outcome Measure Data

Analysis Population Description

Analysis was conducted on intent-to-treat subjects (randomized subjects who received at least 1 dose of study drug) who had sufficient diary data to allow for determination of relief status.

Arm/Group Title	Placebo	Dexlansoprazole 30 mg QD
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole 30 mg, capsules, orally, once daily for up to 4 weeks.
Measure Participants	148	141
Number [Percentage of participants]	19.6 12.8%	47.5 31.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dexlansoprazole 30 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance was only declared if the primary endpoint was statistically significant at 0.05 level. The multiplicity between the two secondary endpoints was adjusted by Hommel-Simes method to maintain the overall 0.05 level.
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Percentage of Participants With Relief of Gastro-Esophageal Reflux Disease (GERD) Associated Sleep Disturbances Over the Last 7 Days of Treatment as Assessed by Daily Diary.
Description	Relief of GERD-associated sleep disturbance was defined as 6 of 7 nights with no GERD associated sleep disturbances; lack of relief of GERD-associated sleep disturbance was defined as 2 or more out of 7 nights with GERD-associated sleep disturbance. Subjects indicate the presence (Yes/No) of GERD associated sleep disturbance in a Daily Electronic Diary. The percentage was calculated as the number of subjects with relief of GERD-associated sleep disturbance divided by the number of subjects whose relief status could be determined.
Time Frame	Last 7 days of treatment

Outcome Measure Data

Analysis Population Description

Analysis was conducted on intent-to-treat subjects (randomized subjects who received at least 1 dose of study drug) who had sufficient diary data to allow for determination of relief status.

Arm/Group Title	Placebo	Dexlansoprazole 30 mg QD
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.	Dexlansoprazole 30 mg, capsules, orally, once daily for up to 4 weeks.
Measure Participants	144	142
Number [Percentage of participants]	47.9 (29.9) 31.3%	69.7 (29.6) 45.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dexlansoprazole 30 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance was only declared if the primary endpoint was statistically significant at 0.05 level. The multiplicity between the two secondary endpoints was adjusted by Hommel-Simes method to maintain the overall 0.05 level.
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Adverse events summarized were reported after the first dose of study drug and no more than 30 days after the last dose.
Adverse Event Reporting Description	Most frequent events are those High Level Terms occurring in at least 5 % of subjects in at least one treatment group.
Arm/Group Title	Placebo		Dexlansoprazole 30 mg QD
Arm/Group Description	Placebo capsules, orally, once daily for up to 4 weeks.		Dexlansoprazole 30 mg, capsules, orally, once daily for up to 4 weeks.
All Cause Mortality
	Placebo		Dexlansoprazole 30 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Dexlansoprazole 30 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/153 (0.7%)		0/152 (0%)
Pregnancy, puerperium and perinatal conditions
Abortions Spontaneous	1/153 (0.7%)	1	0/152 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Dexlansoprazole 30 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/153 (2%)		7/152 (4.6%)
Infections and infestations
Upper Respiratory Tract Infections	3/153 (2%)		7/152 (4.6%)

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 at all study sites. 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.