Gastroesophageal Reflux
Conditions
Keywords
Non-Erosive Gastroesophageal Reflux Disease, GERD, heartburn, sleep disturbance, nocturnal Reflux
Brief summary
The purpose of this study is to determine whether Dexlansoprazole once daily (QD) is effective in treating patients with night heartburn.
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.
Interventions
DRUGDexlansoprazole
30 mg capsule, orally, once daily for 4 weeks
DRUGPlacebo
1 capsule, orally, once daily for 4 weeks
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
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 details
Subjects eligible for entry into the Treatment Period were randomized into one of two, once-daily (QD) treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo capsules, orally, once daily for up to 4 weeks. | 153 |
| Dexlansoprazole 30 mg QD Dexlansoprazole 30 mg, capsules, orally, once daily for up to 4 weeks. | 152 |
| Total | 305 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Failed Inclusion/Exclusion Criteria | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Placed on Excluded Drugs | 1 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Dexlansoprazole 30 mg QD | Placebo |
|---|---|---|---|
| Age Continuous | 44.2 years STANDARD_DEVIATION 11.87 | 44.6 years STANDARD_DEVIATION 11.29 | 43.9 years STANDARD_DEVIATION 12.45 |
| Age, Customized 45 to <65 years | 151 participants | 75 participants | 76 participants |
| Age, Customized <45 years | 150 participants | 75 participants | 75 participants |
| Age, Customized >=65 years | 4 participants | 2 participants | 2 participants |
| Number of Days with Night Heartburn 0-3 days | 13 participants | 3 participants | 10 participants |
| Number of Days with Night Heartburn 4-5 days | 74 participants | 38 participants | 36 participants |
| Number of Days with Night Heartburn 6-7 days | 218 participants | 111 participants | 107 participants |
| Number of Nights with Sleep Disturbances Related to Gastroesophageal Reflux Disease (GERD) Symptoms 0-3 Nights | 73 participants | 33 participants | 40 participants |
| Number of Nights with Sleep Disturbances Related to Gastroesophageal Reflux Disease (GERD) Symptoms 4-5 Nights | 100 participants | 47 participants | 53 participants |
| Number of Nights with Sleep Disturbances Related to Gastroesophageal Reflux Disease (GERD) Symptoms 6-7 Nights | 132 participants | 72 participants | 60 participants |
| Region of Enrollment United States | 305 participants | 152 participants | 153 participants |
| Sex: Female, Male Female | 195 Participants | 97 Participants | 98 Participants |
| Sex: Female, Male Male | 110 Participants | 55 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 153 | 7 / 152 |
| serious Total, serious adverse events | 1 / 153 | 0 / 152 |
Outcome results
Primary
Median Percentage of Nights Without Heartburn Over 4 Weeks as Assessed by Daily Diary.
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
Population: 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 | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Median Percentage of Nights Without Heartburn Over 4 Weeks as Assessed by Daily Diary. | 35.7 Percentage of nights | Inter-Quartile Range 30 |
| Dexlansoprazole 30 mg QD | Median Percentage of Nights Without Heartburn Over 4 Weeks as Assessed by Daily Diary. | 73.1 Percentage of nights | Inter-Quartile Range 35 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
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.
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
Population: 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 | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo | 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. | 47.9 Percentage of participants | 29.9 |
| Dexlansoprazole 30 mg QD | 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. | 69.7 Percentage of participants | 29.6 |
p-value: <0.001Fisher Exact
Secondary
Percent of Subjects With Relief of Night Time Heartburn Over the Last 7 Days of Treatment as Assessed by Daily Diary.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Subjects With Relief of Night Time Heartburn Over the Last 7 Days of Treatment as Assessed by Daily Diary. | 19.6 Percentage of participants |
| Dexlansoprazole 30 mg QD | Percent of Subjects With Relief of Night Time Heartburn Over the Last 7 Days of Treatment as Assessed by Daily Diary. | 47.5 Percentage of participants |
p-value: <0.001Fisher Exact