Gastrointestinal Mucosal Damage
Conditions
Brief summary
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.
Interventions
DRUGIbuprofen
Liquid gelation capsules or tablets of 400 mg strength
DRUGParacetamol
Paracetamol fast dissolving tablets of 500 mg strength
OTHERPlacebo
Placebo tablets
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastromucosal Damage (GMD) Score of Paracetamol Tablet vs Ibuprofen Capsule | Day 7 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GMD Scores of Paracetamol Tablet; Ibuprofen Capsule; Ibuprofen Tablet; and Placebo Tablet | Day 7 | 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. |
| Duodenal Mucosal Damage (DMD) Scores | Day 7 | 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. |
| Incidence of Gastric and/or Duodenal Mucosal Injury | Day 7 | 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. |
| Incidence of Fecal Occult Blood | Day 7 | The incidence of fecal occult blood was recorded as a binary response (0 = no presence of blood; 1 = presence of blood). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the clinical site.
Pre-assignment details
Of 41 participants screened, 12 did not meet the study criterion and one participant withdrew consent. Remaining 28 participants were randomized into the study to received all the four treatments in a sequential manner.
Participants by arm
| Arm | Count |
|---|---|
| All Randomized Participants All randomized participants in the study who took at least one treatment dose. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Other Reason | 5 |
Baseline characteristics
| Characteristic | All Randomized Participants |
|---|---|
| Age, Continuous | 38.1 Years STANDARD_DEVIATION 12.3 |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 28 | 5 / 24 | 4 / 23 | 1 / 23 |
| serious Total, serious adverse events | 0 / 28 | 0 / 24 | 1 / 23 | 0 / 28 |
Outcome results
Primary
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.
Time frame: Day 7
Population: Intent to Treat (ITT) population: all participants who fulfilled all the study entry criteria and receive at least one of the study treatments. The ITT population included all participants with valid data-period. Missing data was not imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paracetamol Tablet (1000 mg) | Gastromucosal Damage (GMD) Score of Paracetamol Tablet vs Ibuprofen Capsule | 0.33 Scores on a scale | Standard Deviation 0.68 |
| Ibuprofen Capsule (400 mg) | Gastromucosal Damage (GMD) Score of Paracetamol Tablet vs Ibuprofen Capsule | 1.48 Scores on a scale | Standard Deviation 1.34 |
Comparison: Null hypothesis considered no significant difference in mean endoscopy score of gastric mucosal damage between two treatments.p-value: <0.000195% CI: [-1.63, -0.59]t-test, 2 sided
Secondary
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.
Time frame: Day 7
Population: ITT population: All participants who fulfilled all the study entry criteria and receive at least one of the study treatments. The ITT population included all participants with valid data-period. Missing data was not imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paracetamol Tablet (1000 mg) | Duodenal Mucosal Damage (DMD) Scores | 0.15 Score on a scale | Standard Deviation 0.77 |
| Ibuprofen Capsule (400 mg) | Duodenal Mucosal Damage (DMD) Scores | 0.26 Score on a scale | Standard Deviation 0.86 |
| Ibuprofen Tablet (400 mg) | Duodenal Mucosal Damage (DMD) Scores | 0.23 Score on a scale | Standard Deviation 0.75 |
| Placebo Tablet | Duodenal Mucosal Damage (DMD) Scores | 0.00 Score on a scale | Standard Deviation 0 |
Comparison: Null hypothesis considered no significant difference in mean endoscopy score of duodenal mucosal damage between two treatments.p-value: 0.649795% CI: [-0.49, 0.31]t-test, 2 sided
Comparison: Null hypothesis considered no significant difference in mean endoscopy score of duodenal mucosal damage between two treatmentsp-value: 0.759195% CI: [-0.46, 0.34]t-test, 2 sided
Comparison: Null hypothesis considered no significant difference in mean endoscopy score of duodenal mucosal damage between two treatments.p-value: 0.412695% CI: [-0.24, 0.57]t-test, 2 sided
Comparison: Null hypothesis considered no significant difference in mean endoscopy score of duodenal mucosal damage between two treatmentsp-value: 0.890395% CI: [-0.39, 0.45]t-test, 2 sided
Comparison: Null hypothesis considered no significant difference in mean endoscopy score of duodenal mucosal damage between two treatmentsp-value: 0.222795% CI: [-0.16, 0.67]t-test, 2 sided
Comparison: Null hypothesis considered no significant difference in mean endoscopy score of duodenal mucosal damage between two treatments.p-value: 0.285595% CI: [-0.2, 0.65]t-test, 2 sided
Secondary
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.
Time frame: Day 7
Population: ITT population: All participants who fulfilled all the study entry criteria and received at least one of the study treatments. The ITT population included all participants with valid data-period. Missing data was not imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paracetamol Tablet (1000 mg) | GMD Scores of Paracetamol Tablet; Ibuprofen Capsule; Ibuprofen Tablet; and Placebo Tablet | 0.33 Score on a scale | Standard Deviation 0.68 |
| Ibuprofen Capsule (400 mg) | GMD Scores of Paracetamol Tablet; Ibuprofen Capsule; Ibuprofen Tablet; and Placebo Tablet | 1.48 Score on a scale | Standard Deviation 1.34 |
| Ibuprofen Tablet (400 mg) | GMD Scores of Paracetamol Tablet; Ibuprofen Capsule; Ibuprofen Tablet; and Placebo Tablet | 1.05 Score on a scale | Standard Deviation 1.33 |
| Placebo Tablet | GMD Scores of Paracetamol Tablet; Ibuprofen Capsule; Ibuprofen Tablet; and Placebo Tablet | 0.14 Score on a scale | Standard Deviation 0.35 |
Comparison: Null hypothesis considered no significant difference in mean endoscopy score of gastric mucosal damage between two treatments.p-value: 0.009595% CI: [-1.23, -0.18]t-test, 2 sided
Comparison: Null hypothesis considered no significant difference in mean endoscopy score of gastric mucosal damage between two treatments.p-value: 0.479495% CI: [-0.34, 0.72]t-test, 2 sided
Comparison: Null hypothesis considered no significant difference in mean endoscopy score of gastric mucosal damage between two treatments.p-value: 0.142995% CI: [-0.14, 0.95]t-test, 2 sided
Comparison: Null hypothesis considered no significant difference in mean endoscopy score of gastric mucosal damage between two treatments.p-value: <0.000195% CI: [0.75, 1.84]t-test, 2 sided
Comparison: Null hypothesis considered no significant difference in mean endoscopy score of gastric mucosal damage between two treatments.p-value: 0.00295% CI: [0.34, 1.45]t-test, 2 sided
Secondary
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).
Time frame: Day 7
Population: ITT population: All participants who fulfilled all the study entry criteria and received at least one of the study treatments. The ITT population included all participants with valid data-period. Missing data was not imputed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paracetamol Tablet (1000 mg) | Incidence of Fecal Occult Blood | Score 0 = no fecal occult blood | 27 Participants |
| Paracetamol Tablet (1000 mg) | Incidence of Fecal Occult Blood | Score 1 = fecal occult blood present | 0 Participants |
| Ibuprofen Capsule (400 mg) | Incidence of Fecal Occult Blood | Score 1 = fecal occult blood present | 0 Participants |
| Ibuprofen Capsule (400 mg) | Incidence of Fecal Occult Blood | Score 0 = no fecal occult blood | 23 Participants |
| Ibuprofen Tablet (400 mg) | Incidence of Fecal Occult Blood | Score 0 = no fecal occult blood | 22 Participants |
| Ibuprofen Tablet (400 mg) | Incidence of Fecal Occult Blood | Score 1 = fecal occult blood present | 0 Participants |
| Placebo Tablet | Incidence of Fecal Occult Blood | Score 0 = no fecal occult blood | 22 Participants |
| Placebo Tablet | Incidence of Fecal Occult Blood | Score 1 = fecal occult blood present | 0 Participants |
Secondary
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.
Time frame: Day 7
Population: ITT population: All participants who fulfilled all the study entry criteria and receive at least one of the study treatments. The ITT population included all participants with valid data-period. Missing data was not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paracetamol Tablet (1000 mg) | Incidence of Gastric and/or Duodenal Mucosal Injury | 12 Participants |
| Ibuprofen Capsule (400 mg) | Incidence of Gastric and/or Duodenal Mucosal Injury | 8 Participants |
| Ibuprofen Tablet (400 mg) | Incidence of Gastric and/or Duodenal Mucosal Injury | 4 Participants |
| Placebo Tablet | Incidence of Gastric and/or Duodenal Mucosal Injury | 0 Participants |
p-value: 0.008495% CI: [1.6, 23.97]Chi-squared
p-value: 0.099995% CI: [0.8, 12.74]Chi-squared
p-value: 0.284595% CI: [0.58, 6.5]Chi-squared