Gastrointestinal Safety Evaluation of Two Over the Counter Analgesics

A Study to Investigate the Gastrointestinal Safety of OTC Analgesics in Healthy Volunteers by Endoscopic Examination

This study evaluated the effect of oral fast-dissolving formulations of paracetamol and ibuprofen on the lining of the stomach and duodenum (gastrointestinal mucosa). Endoscopic examinations were conducted to determine the gastrointestinal damage produced post a 7 day treatment regimen.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Mucosal Damage
• Intervention / Treatment: Other: Placebo; Drug: Paracetamol; Drug: Ibuprofen

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77074
      • Houston Institute for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body Mass Index: 18-30 kg/m^2
• Body Weight 60-80 kg
• Participant with both a normal stomach and proximal duodenum mucosa as evidenced by endoscopic results

Exclusion Criteria:

• Participant with evidence of current/active, or a history of gastrointestinal disease
• Participant with a history of renal disease, pulmonary edema, cardiomyopathy, liver disease, intrinsic coagulation defects, bleeding diseases or anticoagulant therapy
• Participant with a history of using antacids, H2 receptor antagonists, proton pump inhibitors, or misoprostol more than twice a month or has used any of these medications within 1 week of Visit 1.
• Participant with a current or recurrent disease, within 12 months of Visit 1, that could affect the action, absorption, disposition, or excretion of the study treatments or evaluation of the clinical or laboratory tests

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Paracetamol Tablet; Paracetamol 500 mg tablet, 2 tablets administered 4 times a day (QID) with water.	Drug: Paracetamol; Paracetamol fast dissolving tablets of 500 mg strength
Active Comparator: Ibuprofen Tablet; Ibuprofen 400 mg tablet, 2 tablets administered three times a day (TID) with water	Drug: Ibuprofen; Liquid gelation capsules or tablets of 400 mg strength
Placebo Comparator: Placebo Tablet; Placebo tablets, 2 tablets QID administered with water.	Other: Placebo; Placebo tablets
Active Comparator: Ibuprofen Capsule; Ibuprofen 400 mg liquid gel capsules, 2 tablets, TID administered with water	Drug: Ibuprofen; Liquid gelation capsules or tablets of 400 mg strength

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastromucosal Damage (GMD) Score of Paracetamol Tablet vs Ibuprofen Capsule	Endoscopic examination of the upper gastrointestinal mucosa evaluated the extent of mucosal injury to the stomach and the duodenum separately using a 5-point Lanza scale, ranging from 0: normal stomach; 1: mucosal hemorrhages; 2: one or two erosions; 3: numerous areas of erosions; and 4: more than 10 erosions or ulcer.	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMD Scores of Paracetamol Tablet; Ibuprofen Capsule; Ibuprofen Tablet; and Placebo Tablet	Endoscopic examination of the upper gastrointestinal mucosa evaluated the extent of mucosal injury to the stomach and the duodenum separately using a 5-point Lanza scale, ranging from 0: normal stomach; 1: mucosal hemorrhages; 2: one or two erosions; 3: numerous areas of erosions; and 4: more than 10 erosions or ulcer.	Day 7
Duodenal Mucosal Damage (DMD) Scores	DMD was measured using a 5- point Lanza scale: 0 - normal duodenum; 1 - mucosal hemorrhages; 2 - one or two erosions; 3 - numerous areas of erosions and 4 - more than 10 erosions/ ulcers.	Day 7
Incidence of Gastric and/or Duodenal Mucosal Injury	Number of participants with endoscopy score equal to or more than 2 were determined based on Lanza score for both gastric and duodenal mucosal damage.	Day 7
Incidence of Fecal Occult Blood	The incidence of fecal occult blood was recorded as a binary response (0 = no presence of blood; 1 = presence of blood).	Day 7

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: March 28, 2013
• First Submitted That Met QC Criteria: March 28, 2013
• First Posted (Estimate): April 2, 2013

Study Record Updates

• Last Update Posted (Estimate): March 31, 2014
• Last Update Submitted That Met QC Criteria: February 13, 2014
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Acetaminophen; Ibuprofen
• Other Study ID Numbers: A1901106