Gastroesophageal Reflux Disease
Conditions
Keywords
GERD, Gastroesophageal reflux disease, SPD557, Proton pump inhibitors
Brief summary
The purpose of this trial is to investigate the pharmacodynamic effect on reflux parameters of SPD557 tablets (0.5 mg t.i.d., on top of PPI treatment) in patients with Gastroesophageal Reflux Disease (GERD) with persistent symptoms despite taking a stable dose of proton pump inhibitors. Additionally the effect on symptoms will be explored and safety and tolerability will be evaluated.
Interventions
DRUGSPD557
0.5 mg tablet t.i.d. for 4 weeks on top of stable PPI treatment
DRUGplacebo
matching placebo tablet t.i.d. for 4 weeks on top of stable PPI treatment
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Written ICF signed voluntarily before the first trial related activity. 2. Subjects with a history of GERD symptoms (i.e., heartburn and/or regurgitation) during the last 6 months 3. Subjects on a stable dose of PPIs, compliant for at least 6 weeks prior to screening. 4. ≥3 days per week with heartburn and/or regurgitation symptoms of at least moderate severity and a minimum of 25 liquid containing reflux events over 24h (pH/MII monitoring).
Exclusion criteria
1. Subjects with prior endoscopic anti-reflux procedure or major GI surgery or subjects with major GI disorders. 2. Presence of severe and clinically uncontrolled cardiovascular, liver or lung disease, neurologic, cancer or AIDS. 3. Alarm symptoms suggestive of malignancies or organic disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Number of Liquid-containing Reflux Events (pH/MII Monitoring) at 4 Weeks | Baseline and 4 weeks | This is used to characterize gastric reflux events. The measurements were made over a 24-hour period at baseline and again at week 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Number of Days With Heartburn and/or Regurgitation at 4 Weeks | Baseline and 4 weeks | — |
| Change From Baseline in the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) Questionnaire at 4 Weeks | Baseline and 4 weeks | The PAGI-SYM contains 20 items and the scores range from 0 (no symptoms)-5 (very severe symptoms) for each item with a total score of 0-100. Higher scores indicate more severe gastrointestinal symptoms. |
Countries
Belgium, France, Germany, Netherlands, Switzerland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SPD557 0.5 mg tablet t.i.d. for 4 weeks in addition to stable proton pump inhibitor (PPI) treatment | 34 |
| Placebo Matching placebo tablet t.i.d. for 4 weeks in addition to stable PPI treatment | 31 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Did not want second pH/MII monitoring | 1 | 1 |
| Overall Study | Not meeting inclusion/exclusion criteria | 0 | 1 |
Baseline characteristics
| Characteristic | SPD557 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 43.8 years STANDARD_DEVIATION 16.04 | 45.8 years STANDARD_DEVIATION 14.5 | 44.8 years STANDARD_DEVIATION 15.24 |
| Age, Customized Between 18 and 70 years inclusive | 34 Participants | 31 Participants | 65 Participants |
| Region of Enrollment Belgium | 8 Participants | 7 Participants | 15 Participants |
| Region of Enrollment France | 13 Participants | 13 Participants | 26 Participants |
| Region of Enrollment Germany | 4 Participants | 4 Participants | 8 Participants |
| Region of Enrollment Netherlands | 2 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Switzerland | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment United Kingdom | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Female | 19 Participants | 17 Participants | 36 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 34 | 16 / 31 |
| serious Total, serious adverse events | 0 / 34 | 0 / 31 |
Outcome results
Primary
Change From Baseline in the Number of Liquid-containing Reflux Events (pH/MII Monitoring) at 4 Weeks
This is used to characterize gastric reflux events. The measurements were made over a 24-hour period at baseline and again at week 4.
Time frame: Baseline and 4 weeks
Population: Pharmacodynamics Population (PD) defined as all randomized subjects with at least 1 administration of the investigational product and with both a baseline and post-baseline PD assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD557 | Change From Baseline in the Number of Liquid-containing Reflux Events (pH/MII Monitoring) at 4 Weeks | -17.9 Number of Reflux Events | Standard Deviation 59.88 |
| Placebo | Change From Baseline in the Number of Liquid-containing Reflux Events (pH/MII Monitoring) at 4 Weeks | -13.7 Number of Reflux Events | Standard Deviation 37.58 |
p-value: 0.86995% CI: [-19.054, 16.149]ANCOVA
Secondary
Change From Baseline in the Number of Days With Heartburn and/or Regurgitation at 4 Weeks
Time frame: Baseline and 4 weeks
Population: Pharmacodynamics Population (PD) defined as all randomized subjects with at least 1 administration of the investigational product and with both a baseline and post-baseline PD assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD557 | Change From Baseline in the Number of Days With Heartburn and/or Regurgitation at 4 Weeks | -0.90 Number of days | Standard Deviation 1.434 |
| Placebo | Change From Baseline in the Number of Days With Heartburn and/or Regurgitation at 4 Weeks | -0.88 Number of days | Standard Deviation 1.61 |
p-value: 0.48795% CI: [-0.495, 1.024]ANCOVA
Secondary
Change From Baseline in the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) Questionnaire at 4 Weeks
The PAGI-SYM contains 20 items and the scores range from 0 (no symptoms)-5 (very severe symptoms) for each item with a total score of 0-100. Higher scores indicate more severe gastrointestinal symptoms.
Time frame: Baseline and 4 weeks
Population: Pharmacodynamics Population (PD) defined as all randomized subjects with at least 1 administration of the investigational product and with both a baseline and post-baseline PD assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD557 | Change From Baseline in the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) Questionnaire at 4 Weeks | -0.41 Units on a scale | Standard Deviation 0.943 |
| Placebo | Change From Baseline in the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) Questionnaire at 4 Weeks | -0.37 Units on a scale | Standard Deviation 0.76 |
p-value: 0.63795% CI: [-0.501, 0.326]ANCOVA