Gastrointestinal Safety Evaluation of Two Over the Counter Analgesics

Study Overview
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Brief Summary
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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.

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

Conditions
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Gastrointestinal Mucosal Damage

Intervention / Treatment
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* Drug: Ibuprofen
* Drug: Paracetamol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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 |