Clinical trial NCT02632812: Gastrointestinal Integrity After Naproxen + Rebamipide Versus Naproxen + Placebo
Official title: Double-blind Trial on the Gastrointestinal Integrity Evaluation After Daily Naproxen 1100 mg + Rebamipide 200mg for 7 Days Versus Naproxen 1100mg + Placebo for 7 Days
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastrointestinal Lesions
Lead sponsor: Biolab Sanus Farmaceutica
Sponsor class: INDUSTRY
First posted: 2015-12-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Endoscopic Score - Cryer Score
timeFrame: 8 days
measure: Endoscopic Score - Modified Lanza Score
timeFrame: 8 days
measure: Histopathological Score
timeFrame: 8 days
measure: Intragastric pH
timeFrame: 8 days
measure: Presence of H. Pylori by Biopsy
timeFrame: 8 days
measure: Prostaglandin Level (PGE2 Quantification)
timeFrame: 8 days
Secondary outcomes:
measure: Number of Adverse Events
timeFrame: 60 days
Other outcomes:
Locations:
Study officials:
affiliation: Galeno Desenvolvimento de Pesquisas Ltda.
name: Gilberto De Nucci, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gagliano-Juca T, Moreno RA, Zaminelli T, Napolitano M, Magalhaes AF, Carvalhaes A, Trevisan MS, Wallace JL, De Nucci G. Rebamipide does not protect against naproxen-induced gastric damage: a randomized double-blind controlled trial. BMC Gastroenterol. 2016 Jun 4;16(1):58. doi: 10.1186/s12876-016-0472-x.