Gastrointestinal Integrity After Naproxen + Rebamipide Versus Naproxen + Placebo
Condition: Gastrointestinal Lesions
Intervention: Rebamipide effervescent granules; Placebo effervescent granules; Naproxen tablet
Intervention description: Rebamipide effervescent granules 100mg (oral), twice daily for 7 days; Placebo effervescent granules (oral), twice daily for 7 days; Naproxen tablet 550mg (tablet), twice daily for 7 days
Intervention MeSH terms: Naproxen; Rebamipide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This is a double-blind, placebo-controlled, randomized, parallel trial to evaluate if
      rebamipide reduces the number of gastric events caused by naproxen. Sample size is 24
      participants (12 per treatment group), male or female, aged 18 years-old and above.

      Primary objective is to compare rebamipide effervescent granules 100 mg twice daily, plus
      naproxen (coated tablets) 550 mg twice daily to placebo plus naproxen 550 mg twice daily, for
      seven days, in reduction of gastric events caused by naproxen. Secondary objective is to
      evaluate safety and tolerability of rebamipide after multiple administrations.

      Participants will receive either rebamipide + naproxen or placebo + naproxen, as above,
      during 7 consecutive days, which will be accompanied by a follow-up visit.

      Gastric integrity will be assessed, before and after treatment, by endoscopy, with stomach
      biopsies and detection of H. pylori. Additionally, detection of occult blood in the stool
      will be performed, before and after treatment.

      From the above-mentioned biopsies, dosage of prostaglandin E2 and histopathological analysis
      will be performed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female study participants, aged 18 years-old and above; women cannot be
             pregnant or breastfeeding;

          -  Body mass index (BMI) greater than or equal to 19 and less than or equal to 28.75
             Kg/m2;

          -  Good health conditions or without significant diseases, according to best medical
             judgement, according to protocol requirements and study evaluations: medical history,
             blood pressure and heart rate measurements, physical examination, electrocardiogram
             (ECG) and screening laboratory tests;

          -  Ability to understand the nature and objectives of the trial, including risks and
             adverse events; willingness to cooperate with the researcher and proceed according to
             all study requirements, which shall be confirmed by Informed Consent Form signature.

        Exclusion Criteria:

          -  Known hypersensitivity to the investigational products (naproxen or rebamipide) or
             chemically related compounds; history of serious adverse reactions or hypersensitivity
             to any drug;

          -  Subject does not present intact superior gastrointestinal mucosa, i.e., presenting
             bleeding, ulcers and apparent injuries in baseline endoscopy;

          -  Subject has achlorhydria (intragastric pH > 6.5);

          -  History or presence of hepatic or gastrointestinal diseases, or other condition that
             interferes with drug absorption, distribution, excretion or metabolism;

          -  Chronic therapy with any drugs, except oral contraceptives;

          -  History of hepatic, kidney, lungs, gastrointestinal, epileptic, hematologic or
             psychiatric disease; hypotension or hypertension, of any etiology, that requires
             pharmacological treatment; history of myocardial infarction, angina and/or heart
             failure;

          -  Occult blood in the stool before treatment;

          -  Electrocardiographic findings that, at investigator criteria, are not recommended for
             study participation;

          -  Deviations on screening laboratory results that are considered as clinically relevant
             by the principal investigator;

          -  History of drugs and alcohol addiction or excessive alcohol consumption (> 35 g/day);

          -  Use of regular medications within 2 weeks prior study enrollment or use of any
             medications within one week prior to study enrollment, except oral contraceptives or
             cases which, based on drug's or metabolite's half-life, complete elimination can be
             assumed;

          -  Treatment, within 6 months before the trial, with any drugs known to have a
             well-established toxic potential to major organs;

          -  Participation in any other experimental research or administration of any experimental
             drug within 6 months before this trial;

          -  Any condition, according to investigator's best judgement, that prevents the subject
             to participate in the trial;

          -  Pregnancy, labor or miscarriage with 12 weeks before admission predicted date.