Gastroesophageal Reflux Disease, Heartburn, Regurgitation
Conditions
Keywords
GERD treatment, Acid and non-acid Reflux, Heartburn, Regurgitation, Add-on treatment to PPI
Brief summary
This study is being carried out to see whether AZD3355 is an effective treatment as an add-on to PPI therapy in patients with Gastroesophageal Reflux Disease (GERD) with a partial response to PPI and to compare this with Proton Pump Inhibitor (PPI) treatment alone. Another goal of the study is to examine which of the investigated doses of AZD3355 is optimal for treatment of these patients. This study will also measure levels of drug in the blood and see how well it is tolerated.
Interventions
DRUGlesogaberan (AZD3355)
60 mg, oral, capsules, bid for 4 w
DRUGPlacebo
oral,capsules, bid for 4 w
Sponsors
AstraZeneca
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
* Provision of informed consent prior to any study specific procedures * Have at least 6 months history of GERD * Continuously treated during the last 4 weeks before enrolment with daily optimized unchanged PPI therapy for any GERD indication
Exclusion criteria
* Patients that have not experienced any GERD symptom improvement at all during PPI treatment * Prior surgery of the upper gastrointestinal tract. * Subject who have any of the following conditions or diseases: Heart disease, Angina, Seizure disorders such as epilepsy, Congestive Heart Failure (CHF), Liver disease such as Cirrhosis or Hepatitis, Kidney disease, Lung disease or lung cancer, Cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Change in GERD Symptoms Corresponding to at Least Three More Days of Not More Than Mild Symptoms on Average Per Week During Treatment (Approximately 4 Weeks) Than During Baseline (the 7 Days Before Randomisation) | The 7 days before randomisation (baseline) and during 26-30 days of treatment | Symptom intensity rated by participants twice daily on a six-graded Likert scale (Did not have; Very mild; Mild; Moderate; Moderately severe; Severe) using an electronic Reflux Symptom Questionnaire diary. (GERD = Gastroesophageal Reflux Disease) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline to Treatment Period in Percent Days With at Most Mild GERD Symptoms. | The 7 days before randomisation (baseline) and during 26-30 days of treatment | Symptom intensity rated by participants twice daily on a six-graded Likert scale (Did not have; Very mild; Mild; Moderate; Moderately severe; Severe) using an electronic Reflux Symptom Questionnaire diary (GERD = Gastroesophageal Reflux Disease) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AZD3355 60 mg PPI+AZD3355 60 mg twice daily (bid) | 134 |
| AZD3355 120 mg PPI+AZD3355 120 mg twice daily (bid) | 125 |
| AZD3355 180 mg PPI+AZD3355 180 mg twice daily (bid) | 136 |
| AZD3355 240 mg PPI+AZD3355 240 mg twice daily (bid) | 126 |
| Placebo PPI+Placebo | 140 |
| Total | 661 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 6 | 8 | 5 | 4 |
| Overall Study | Developed study-specific withdrawal crit | 2 | 0 | 3 | 0 | 1 |
| Overall Study | Eligibility criteria not fulfilled | 4 | 0 | 4 | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 4 | 2 | 0 | 0 |
| Overall Study | Patient moved | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 | 2 |
| Overall Study | Randomized in error | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 5 | 3 | 4 | 9 |
| Overall Study | Wrong drug dispensed | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | AZD3355 60 mg | AZD3355 120 mg | AZD3355 180 mg | AZD3355 240 mg | Placebo | Total |
|---|---|---|---|---|---|---|
| Age Continuous | 47.4 years STANDARD_DEVIATION 12.3 | 46.1 years STANDARD_DEVIATION 13.5 | 48.0 years STANDARD_DEVIATION 12.3 | 48.5 years STANDARD_DEVIATION 12.1 | 48.3 years STANDARD_DEVIATION 12 | 47.7 years STANDARD_DEVIATION 12.4 |
| Sex: Female, Male Female | 84 Participants | 75 Participants | 75 Participants | 75 Participants | 67 Participants | 376 Participants |
| Sex: Female, Male Male | 50 Participants | 50 Participants | 61 Participants | 51 Participants | 73 Participants | 285 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / — | 12 / — | 16 / — | 20 / — | 9 / — |
| serious Total, serious adverse events | 0 / — | 0 / — | 0 / — | 1 / — | 1 / — |
Outcome results
Primary
Number of Participants With a Change in GERD Symptoms Corresponding to at Least Three More Days of Not More Than Mild Symptoms on Average Per Week During Treatment (Approximately 4 Weeks) Than During Baseline (the 7 Days Before Randomisation)
Symptom intensity rated by participants twice daily on a six-graded Likert scale (Did not have; Very mild; Mild; Moderate; Moderately severe; Severe) using an electronic Reflux Symptom Questionnaire diary. (GERD = Gastroesophageal Reflux Disease)
Time frame: The 7 days before randomisation (baseline) and during 26-30 days of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD3355 60 mg | Number of Participants With a Change in GERD Symptoms Corresponding to at Least Three More Days of Not More Than Mild Symptoms on Average Per Week During Treatment (Approximately 4 Weeks) Than During Baseline (the 7 Days Before Randomisation) | 28 Participants |
| AZD3355 120 mg | Number of Participants With a Change in GERD Symptoms Corresponding to at Least Three More Days of Not More Than Mild Symptoms on Average Per Week During Treatment (Approximately 4 Weeks) Than During Baseline (the 7 Days Before Randomisation) | 32 Participants |
| AZD3355 180 mg | Number of Participants With a Change in GERD Symptoms Corresponding to at Least Three More Days of Not More Than Mild Symptoms on Average Per Week During Treatment (Approximately 4 Weeks) Than During Baseline (the 7 Days Before Randomisation) | 32 Participants |
| AZD3355 240 mg | Number of Participants With a Change in GERD Symptoms Corresponding to at Least Three More Days of Not More Than Mild Symptoms on Average Per Week During Treatment (Approximately 4 Weeks) Than During Baseline (the 7 Days Before Randomisation) | 33 Participants |
| Placebo | Number of Participants With a Change in GERD Symptoms Corresponding to at Least Three More Days of Not More Than Mild Symptoms on Average Per Week During Treatment (Approximately 4 Weeks) Than During Baseline (the 7 Days Before Randomisation) | 25 Participants |
Secondary
Absolute Change From Baseline to Treatment Period in Percent Days With at Most Mild GERD Symptoms.
Symptom intensity rated by participants twice daily on a six-graded Likert scale (Did not have; Very mild; Mild; Moderate; Moderately severe; Severe) using an electronic Reflux Symptom Questionnaire diary (GERD = Gastroesophageal Reflux Disease)
Time frame: The 7 days before randomisation (baseline) and during 26-30 days of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD3355 60 mg | Absolute Change From Baseline to Treatment Period in Percent Days With at Most Mild GERD Symptoms. | 10.7 Percent |
| AZD3355 120 mg | Absolute Change From Baseline to Treatment Period in Percent Days With at Most Mild GERD Symptoms. | 17.2 Percent |
| AZD3355 180 mg | Absolute Change From Baseline to Treatment Period in Percent Days With at Most Mild GERD Symptoms. | 11.9 Percent |
| AZD3355 240 mg | Absolute Change From Baseline to Treatment Period in Percent Days With at Most Mild GERD Symptoms. | 12.5 Percent |
| Placebo | Absolute Change From Baseline to Treatment Period in Percent Days With at Most Mild GERD Symptoms. | 0 Percent |