NCT02632812

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.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Oct 2014

Shorter than P25 for phase_1

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2014

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2014

Completed
1.1 years until next milestone

First Submitted

Initial submission to the registry

November 23, 2015

Completed
24 days until next milestone

First Posted

Study publicly available on registry

December 17, 2015

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

March 20, 2017

Completed
Last Updated

March 20, 2017

Status Verified

January 1, 2017

Enrollment Period

1 month

First QC Date

November 23, 2015

Results QC Date

March 18, 2016

Last Update Submit

January 31, 2017

Conditions

Gastrointestinal Lesions

Outcome Measures

Primary Outcomes (6)

  • Endoscopic Score - Cryer Score

    Cryer score according to gastroduodenal mucosal injury: 0 = Normal or erythema 1. = Any amount of submucosal hemorrhage or edema without erosions 2. = 1 erosion +- submucosal hemorrhage or edema 3. = 2-4 erosions +- submucosal hemorrhage or edema 4. = 5 or more erosions and/or a single ulcer +- submucosal hemorrhage or edema 5. = Multiple ulcers +- submucosal hemorrhage or edema - Ulcer

    8 days

  • Endoscopic Score - Modified Lanza Score

    Modified Lanza score according to gastroduodenal mucosal injury: 0 = No hemorrhage or erosion observed 1. = One or two hemorrhages or erosions observed in one gastric area 2. = Three to five hemorrhages or erosions observed in one gastric area 3. = Hemorrhages or erosions observed in two gastric areas, six or more hemorrhages or erosions observed in one gastric area, with the total number not exceeding ten in the entire stomach 4. = Hemorrhages or erosions observed in three or more gastric areas; eleven or more hemorrhages or erosions observed widely in the entire stomach 5. = Ulcer

    8 days

  • Histopathological Score

    Histopathologic grade score developed for microscopic injury evaluation 0 = Normal gastric mucosa or mild chronic inflammation 1. = Chronic gastritis without activity 2. = Chronic gastritis with activity on antrum 3. = Chronic gastritis with activity on the body 4. = Chronic gastritis with activity on antrum and on the body

    8 days

  • Intragastric pH

    8 days

  • Presence of H. Pylori by Biopsy

    Giemsa stain was used to diagnose H. pylori (positive = presence of H. pylori)

    8 days

  • Prostaglandin Level (PGE2 Quantification)

    Tissue prostaglandin concentration quantified by enzyme-linked immunosorbent assay (ELISA) using Cayman Chemical Monoclonal Prostaglandin E2 EIA Kit (item number 514010)

    8 days

Secondary Outcomes (1)

  • Number of Adverse Events

    60 days

Study Arms (2)

Rebamipide & Naproxen

EXPERIMENTAL

Rebamipide 100 mg effervescent granules (oral) Twice daily (total dose = 200 mg) for 7 days

Drug: Rebamipide effervescent granulesDrug: Naproxen tablet

Placebo & Naproxen

PLACEBO COMPARATOR

Sugar pill manufactured to mimic Rebamipide 100 mg effervescent granules (oral) Twice daily for 7 days

Drug: Placebo effervescent granulesDrug: Naproxen tablet

Interventions

Rebamipide effervescent granulesDRUG

Rebamipide effervescent granules 100mg (oral), twice daily for 7 days

Rebamipide & Naproxen
Placebo effervescent granulesDRUG

Placebo effervescent granules (oral), twice daily for 7 days

Placebo & Naproxen
Naproxen tabletDRUG

Naproxen tablet 550mg (tablet), twice daily for 7 days

Placebo & NaproxenRebamipide & Naproxen

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • 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.

    PMID: 27259970DERIVED

MeSH Terms

Interventions

Naproxen

Intervention Hierarchy (Ancestors)

Naphthaleneacetic AcidsNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Results Point of Contact

Title
Gilberto De Nucci, PhD, principal investigator
Organization
Galeno Desenvolvimento de Pesquisas Ltda.
denucci@gilbertodenucci.com
55.19.32516928

Study Officials

  • Gilberto De Nucci, PhD

    Galeno Desenvolvimento de Pesquisas Ltda.

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 23, 2015

First Posted

December 17, 2015

Study Start

October 1, 2014

Primary Completion

November 1, 2014

Study Completion

November 1, 2014

Last Updated

March 20, 2017

Results First Posted

March 20, 2017

Record last verified: 2017-01

Data Sharing

IPD Sharing
Will not share