ERADICATE Hp2 - Treating Helicobacter Pylori With RHB-105 Compared to Active Comparator
Condition: Helicobacter Pylori Infection; Dyspepsia
MeSH terms: Infections; Dyspepsia
Intervention: RHB-105; Active Comparator
Intervention description: The intended dose of RHB-105 (12.5 mg rifabutin, 250 mg amoxicillin, and 10 mg omeprazole capsules) 4 capsules every eight hours, is equivalent to a total daily dose of:
Rifabutin 150 mg
Amoxicillin 3000 mg
Omeprazole 120 mg
One 50mg Riboflavin tablet to be taken once daily to maintain the blind.; The intended dose of the Active Comparator (250 mg amoxicillin, and 10 mg omeprazole capsules) 4 capsules every eight hours, equivalent to a total daily dose of:
Amoxicillin 3000 mg
Omeprazole 120 mg
One 50mg Riboflavin tablet to be taken once daily to maintain the blind.
Intervention MeSH terms: Amoxicillin; Rifabutin; Omeprazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 455.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

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 against an active
      comparator.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be ages 18 - 70, inclusive; non-Asian males and females (This population has been
             demonstrated to have significantly elevated omeprazole levels as per the prescriber
             information for other omeprazole products). A person having origins in any of the
             original peoples of the Far East, Southeast Asia, or the Indian subcontinent,
             including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the
             Philippine Islands, Thailand, and Vietnam should be considered Asian, and forr this
             study Asian is defined as having at least one Asian grandparent (Shektar et al, 2014,
             FDA Guidance for Industry 2016);

          2. Positive for H. pylori by 13C Urea Breath Test (UBT) and confirmed positive via
             gastric biopsy for campylobacter-like organism (CLO) Rapid Urease Test, or H. pylori
             culture or histology;

          3. 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);

          4. Females must not be pregnant or lactating and:

               1. at no risk of pregnancy for one of the following reasons: postmenopausal for at
                  least one year from the date of informed consent, status post hysterectomy or
                  tubal ligation, OR

               2. are prepared to and agree to use of an intrauterine device (IUD) or practice
                  double method birth control (barrier plus spermicide) from screening through to
                  30 days post-end of-treatment (EOT); Acceptable double contraceptive methods
                  include barrier (condoms or diaphragms) plus spermicide

               3. Hormonal contraceptives (birth control pills and hormone implants) are not
                  acceptable contraception methods under this protocol;

          5. Males must be surgically sterilized or are prepared to and agree to practice double
             method (barrier plus spermicide) birth control from screening through to 30 days
             post-EOT;

          6. Agree to refrain from consuming alcohol from 1 week prior to screening to Test of
             Cure/Visit 5;

          7. Agree to refrain from taking antacids from screening through day 15 and for at least
             24 hours prior to Test of Cure/Visit 5 and if applicable at least 24 hours prior to
             Visit 8/Test of Cure;

          8. Agree to refrain from taking H2 blockers at least 24 hours prior to screening 13C UBT
             and at least 24 hours prior to Test of Cure/Visit 5 and if applicable at least 24
             hours prior to Visit 8/Test of Cure;

          9. Agree to refrain from taking sucralfate from one week prior to screening through Test
             of Cure/Visit5;

         10. Agree to refrain from taking bismuth containing medications such as Pepto-BismolTM or
             other proton pump inhibitors (PPIs) from two weeks prior to screening through Test of
             Cure/Visit 5;

         11. Agrees to refrain from consuming grapefruit, or any other food or supplement known to
             significantly affect CYP3A4 or CYP2C19 activity from screening to day 15;

         12. Provide written informed consent to participate as shown by a signature of subject on
             the consent form.

        Exclusion Criteria:

          1. Have alarm symptoms/signs (including unexplained anemia [iron deficiency], melena /
             hematemesis, anorexia, dysphagia, jaundice, weight loss);

          2. Have received prior H. pylori eradication therapy;

          3. Use of antibiotics in the 4 weeks immediately prior to screening 13C UBT;

          4. Use of any proton pump inhibitors (PPIs) or bismuth-containing medications (such as
             Pepto-BismolTM) within the 2 weeks immediately prior to screening 13C UBT;

          5. Use of any of the following medications within seven days prior screening: alfentanil,
             allopurinol, amlodipine, anti-herpes agents, anti-retroviral agents, apixaban,
             aprepitant, aripiprazole, astemizole, atorvastatin, boceprevir, buspirone,
             carbamazepine, cisapride, citalopram dosed greater than 20 mg /d, clomipramine,
             clopidogrel and other oral anticoagulants, colchicine, dapsone, dihydroergotamine,
             digoxin, diltiazem, ergotamine, felodipine, fluconazole, gleevec, hormonal
             contraceptives that are not exclusively norethindrone or norgestrel, imipramine,
             itraconazole, ketoconazole, latuda, lovastatin, mycophenolate mofetil, nifedipine,
             nisoldipine, nitrendipine, phenytoin, pimozide, probenecid, proguanil, quinine,
             roflumilast, terfenadine and voriconazole;

          6. Use of amiodarone;

          7. Presence of more than two active gastric and/or duodenal ulcers;

          8. History of gastric outlet obstruction; or hypersecretory state (e.g., Zollinger
             Ellison Syndrome);

          9. History of esophageal or gastric surgery, except for simple closure of perforated
             ulcer;

         10. History of gastric cancer;

         11. History of malignancy within the past five years except for basal cell carcinoma of
             the skin or carcinoma in situ of the cervix that has been treated with no evidence of
             recurrence;

         12. Positive screening laboratory results for human immunodeficiency virus (HIV) antibody
             (HIV1 or HIV2), or hepatitis B surface antigen (HBs Ag), or hepatitis C antibody (HCV
             Ab), unless patient has documented sustained viral response evidenced by prior and/or
             current absence of viral RNA at least 24 weeks after completing antiviral therapy;

         13. Current drug or alcohol abuse or history of drug or alcohol abuse in the past 5 years
             from screening;

         14. Known hypersensitivity or suspected history of hypersensitivity reactions to any of
             the study drugs or related drugs, including cephalosporins and penicillin;

         15. Clinical evidence of any disease that in the opinion of the investigator might
             interfere with the subject's ability to participate in the trial;

         16. History of QT prolongation (QTc greater than 450ms in males and 460ms in females), or
             ventricular arrhythmia, including torsades de pointes;

         17. Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) >3x Upper Limit of
             Normal (ULN), or Alkaline Phosphatase (APO4) >2x ULN, or Total Bilirubin >2x ULN.
             Subjects with confirmed diagnosis of Gilbert's Syndrome are excluded if Total
             Bilirubin > 2.5x ULN;

         18. Unable to communicate well with the Investigators and to comply with the study
             requirements;

         19. Involved in any other experimental drug or device protocol (outside of this RHB-105-02
             study) within the 4 weeks immediately prior to screening visit through end of study;

         20. Subjects with creatinine clearance less than 30 ml/min at screening via estimated
             Cockcroft-Gault (eCGF) formula: eCGF or estimated creatinine clearance = [140 - age in
             years] * weight (kg) / 72 * Serum Creatinine (mg/dl) [multiply estimated rate by 0.85
             for women], using actual body weight at screening.