Dyspepsia, Helicobacter Pylori Infection
Conditions
Keywords
Helicobacter pylori, H. pylori, Dyspepsia
Brief summary
The test and treat strategy for treating dyspeptic patients who are H. pylori positive is rapidly becoming the standard of care. This study will test the effectiveness of RHB-105, a new triple therapy to treat H. pylori infection in dyspeptic patients.
Detailed description
This is a, randomized, double-blind, placebo-controlled study of RHB-105 in adult subjects complaining of epigastric discomfort that have been screened and found to be positive for H. pylori infection via 13C Urea Breath Test (UBT) and either fecal antigen test or CLO test. Eligible subjects will be randomized in a ratio of 1:2 between placebo arm (n=30) and the active arm (RHB-105) (n=60). Subjects will receive study drug for 14 consecutive days. Eradication of H. pylori infection will be determined based on 13C UBT conducted between 28 to 56 days after completion of study drug therapy. Subjects will be unblinded upon 13C UBT analysis. This will provide timely active therapy to all subjects enrolled in this study. Subjects in the placebo arm will be entitled to receive standard-of-care as prescribed by the treating physician following un-blinding. Eradication failures (13C UBT-positive) in the active study drug arm will undergo upper endoscopy with sampling for culture and sensitivity testing (to rifabutin, amoxicillin, clarithromycin, and metronidazole). Culture and sensitivity directed therapy as prescribed by the treating physician will be offered to these subjects.
Interventions
DRUGRHB-105
The intended dose is RHB-105 (12.5 mg rifabutin, 250 mg amoxicillin, and 10 mg omeprazole capsules) 4 capsules every eight hours, equivalent to a total daily dose of: * Rifabutin 150 mg * Amoxicillin 3000 mg * Omeprazole 120 mg Subjects will take study drug every 8 hours with food for 14 consecutive days.
DRUGPlacebo
Subjects will take 4 placebo capsules every 8 hours with food for 14 days.
Sponsors
RedHill Biopharma Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Be ≥18 years of age and ≤ 65 years 2. Have symptoms consistent with dyspepsia of at least two weeks duration (defined as recurrent pain or discomfort centered in the upper abdomen, often with a relation to meals) 3. Be positive for H. pylori by 13C Urea Breath Test (UBT) and also by fecal antigen test 4. Be informed of the nature of the study and provide written informed consent before any study specific procedures are performed (or have a legally authorized representative sign consent)
Exclusion criteria
1. Have alarm symptoms/signs (including unexplained anemia \[iron deficiency), melena / hematemesis, anorexia, dysphagia, jaundice, weight loss) 2. Have taken antibiotics in the 4 weeks prior to screening 3. Have taken bismuth containing medications such as peptobismol in the 4 weeks prior to screening 4. Have a history of any previous esophageal or gastric surgery, except for simple closure of perforated ulcer 5. Have a history of gastric outlet obstruction 6. Have a history of hypersecretory state such as Zollinger-Ellison Syndrome 7. Have a history of gastric cancer 8. Have the presence of active gastric and duodenal ulcers or presence of 3 or more active ulcers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Occurrence of H. Pylori Eradication as Confirmed Via 13C UBT Testing | 28-56 days after completion of treatment | Modified intent-to-treat (mITT) population analyzed included all participants whok received at least 1 dose of study drug and underwent a 13C Urea Breath Test (UBT) at Visit 4. Participants with negative test results were to be considered treatment successes. Patients who tested positive for H. pylori infection, and those with indeterminate, not assessable, or missing results were to be considered treatment failures. The statistical hypothesis that the active treatment is superior to 70% was to be tested against the alternative hypothesis that the active treatment is statistically indistinguishable or less than 70% effective using a one-sample Z-test. |
Other
| Measure | Time frame | Description |
|---|---|---|
| H. Pylori Eradication | 28-56 days after completion of SOC treatment | The occurrence of H. pylori eradication in Placebo and Active Drug Eradication Failure Patients treated with Standard of Care (SOC) treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RHB-105 RHB-105 is an 'all-in-one' combination oral capsule consisting of 2 different antibiotics and a proton pump inhibitor combined in a single capsule.
Total daily dose of: Rifabutin 150 mg, Amoxicillin 3000 mg and Omeprazole 120 mg. | 77 |
| Placebo Capsules that look like the RHB-105 product but contain no active ingredient. | 41 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 6 | 7 |
| Overall Study | Poor compliance | 5 | 0 |
| Overall Study | Randomized by mistake | 1 | 0 |
| Overall Study | Safety issue | 0 | 1 |
| Overall Study | Study drug discontinued | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | RHB-105 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 46.2 years STANDARD_DEVIATION 10.56 | 45.8 years STANDARD_DEVIATION 9.52 | 46 years STANDARD_DEVIATION 10.18 |
| Sex: Female, Male Female | 28 Participants | 16 Participants | 44 Participants |
| Sex: Female, Male Male | 49 Participants | 25 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 77 | 17 / 41 |
| serious Total, serious adverse events | 1 / 77 | 1 / 41 |
Outcome results
Primary
The Occurrence of H. Pylori Eradication as Confirmed Via 13C UBT Testing
Modified intent-to-treat (mITT) population analyzed included all participants whok received at least 1 dose of study drug and underwent a 13C Urea Breath Test (UBT) at Visit 4. Participants with negative test results were to be considered treatment successes. Patients who tested positive for H. pylori infection, and those with indeterminate, not assessable, or missing results were to be considered treatment failures. The statistical hypothesis that the active treatment is superior to 70% was to be tested against the alternative hypothesis that the active treatment is statistically indistinguishable or less than 70% effective using a one-sample Z-test.
Time frame: 28-56 days after completion of treatment
Population: The mITT Population included all subjects who received at least 1 dose of randomized study treatment and underwent a 13C UBT test at Visit 4. This population consisted in 66 subjects in the RHB-105 group and 37 subjects in the placebo group.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RHB-105 | The Occurrence of H. Pylori Eradication as Confirmed Via 13C UBT Testing | H. pylori eradication success | 59 Participants |
| RHB-105 | The Occurrence of H. Pylori Eradication as Confirmed Via 13C UBT Testing | H. pylori eradication failure | 7 Participants |
| Placebo | The Occurrence of H. Pylori Eradication as Confirmed Via 13C UBT Testing | H. pylori eradication success | 1 Participants |
| Placebo | The Occurrence of H. Pylori Eradication as Confirmed Via 13C UBT Testing | H. pylori eradication failure | 36 Participants |
p-value: 0.001One-sample Z-test, RHB-105 subjects only
Other Pre-specified
H. Pylori Eradication
The occurrence of H. pylori eradication in Placebo and Active Drug Eradication Failure Patients treated with Standard of Care (SOC) treatment
Time frame: 28-56 days after completion of SOC treatment
Population: Eradication Failure Subjects at Visit 4 were treated with standard of care therapy by the investigator and performed a 13C Urea Breath Test at Visit 8 to confirm H. pylori eradication. This population included 27 subjects in the placebo group and 4 subjects in the active drug eradication failure subjects.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RHB-105 | H. Pylori Eradication | H. pylori eradication success | 17 Participants |
| RHB-105 | H. Pylori Eradication | H. pylori eradication failure | 10 Participants |
| Placebo | H. Pylori Eradication | H. pylori eradication success | 2 Participants |
| Placebo | H. Pylori Eradication | H. pylori eradication failure | 2 Participants |