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CompletedNCT01822665Updated Mar 31, 2014Results posted

Gastrointestinal Safety Evaluation of Two Over the Counter Analgesics

A Phase 4 interventional study of Ibuprofen and Paracetamol in Gastrointestinal Mucosal Damage, sponsored by GlaxoSmithKline. Completed at 1 site in United States. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-03-31.

Sponsored by GlaxoSmithKline · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
28
Allocation
Randomized
Ages
18 Years to 60 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Gastrointestinal Mucosal Damage
03

In context

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts 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

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
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Single (Outcomes assessor)
Enrollment
28 participants (actual)

Study arms

  • Active comparator
    Paracetamol Tablet

    Paracetamol 500 mg tablet, 2 tablets administered 4 times a day (QID) with water.

    Drug: Paracetamol

  • Active comparator
    Ibuprofen Tablet

    Ibuprofen 400 mg tablet, 2 tablets administered three times a day (TID) with water

    Drug: Ibuprofen

  • Placebo comparator
    Placebo Tablet

    Placebo tablets, 2 tablets QID administered with water.

    Other: Placebo

  • Active comparator
    Ibuprofen Capsule

    Ibuprofen 400 mg liquid gel capsules, 2 tablets, TID administered with water

    Drug: Ibuprofen

Interventions

  • DrugIbuprofen

    Liquid gelation capsules or tablets of 400 mg strength

  • DrugParacetamol

    Paracetamol fast dissolving tablets of 500 mg strength

  • OtherPlacebo

    Placebo tablets

06

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

07

Results

Posted Mar 31, 2014

Participant flow

Participants were recruited at the clinical site.

Participant flow — Overall Study
MilestoneOverall Study
Started28
Received ibuprofen tablet (400 mg)23
Received placebo tablet23
Received ibuprofen capsule (400 mg)24
Received paracetamol tablet (1000 mg)28
Completed20
Not completed8
Withdrew: Adverse event3
Withdrew: Other reason5

Outcome measures

PrimaryGastromucosal 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
Reported as:
Mean · Scores on a scale
Gastromucosal Damage (GMD) Score of Paracetamol Tablet vs Ibuprofen Capsule
Scores on a scaleParacetamol Tablet (1000 mg)Ibuprofen Capsule (400 mg)
Gastromucosal Damage (GMD) Score of Paracetamol Tablet vs Ibuprofen Capsule0.33 ± 0.681.48 ± 1.34
Statistical analysis
  • Paracetamol Tablet (1000 mg) vs Ibuprofen Capsule (400 mg) · t-test, 2 sided · p = <0.0001 (No multiple comparisons were carried out.) · Least squares mean difference: -1.11 · 95% CI -1.63 to -0.59Difference was first named treatment minus second named treatment, such that a positive difference favors the first named treatment.
SecondaryGMD 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
Reported as:
Mean · Score on a scale
GMD Scores of Paracetamol Tablet; Ibuprofen Capsule; Ibuprofen Tablet; and Placebo Tablet
Score on a scaleParacetamol Tablet (1000 mg)Ibuprofen Capsule (400 mg)Ibuprofen Tablet (400 mg)Placebo Tablet
GMD Scores of Paracetamol Tablet; Ibuprofen Capsule; Ibuprofen Tablet; and Placebo Tablet0.33 ± 0.681.48 ± 1.341.05 ± 1.330.14 ± 0.35
Statistical analysis
  • Paracetamol Tablet (1000 mg) vs Ibuprofen Tablet (400 mg) · t-test, 2 sided · p = 0.0095 · Ls mean difference: -0.70 · 95% CI -1.23 to -0.18Difference was first named treatment minus second named treatment, such that a positive difference favors the first named treatment.
  • Paracetamol Tablet (1000 mg) vs Placebo Tablet · t-test, 2 sided · p = 0.4794 (No multiple comparisons were carried out.) · Ls mean difference: 0.19 · 95% CI -0.34 to 0.72Difference was first named treatment minus second named treatment, such that a positive difference favors the first named treatment.
  • Ibuprofen Capsule (400 mg) vs Ibuprofen Tablet (400 mg) · t-test, 2 sided · p = 0.1429 (No multiple comparisons were carried out.) · Ls mean difference: 0.40 · 95% CI -0.14 to 0.95Difference was first named treatment minus second named treatment, such that a positive difference favors the first named treatment.
  • Ibuprofen Capsule (400 mg) vs Placebo Tablet · t-test, 2 sided · p = <0.0001 (No multiple comparisons were carried out.) · Ls mean difference: 1.30 · 95% CI 0.75 to 1.84Difference was first named treatment minus second named treatment, such that a positive difference favors the first named treatment.
  • Ibuprofen Tablet (400 mg) vs Placebo Tablet · t-test, 2 sided · p = 0.0020 (No multiple comparisons were carried out.) · Ls mean difference: 0.89 · 95% CI 0.34 to 1.45Difference was first named treatment minus second named treatment, such that a positive difference favors the first named treatment.
SecondaryDuodenal 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
Reported as:
Mean · Score on a scale
Duodenal Mucosal Damage (DMD) Scores
Score on a scaleParacetamol Tablet (1000 mg)Ibuprofen Capsule (400 mg)Ibuprofen Tablet (400 mg)Placebo Tablet
Duodenal Mucosal Damage (DMD) Scores0.15 ± 0.770.26 ± 0.860.23 ± 0.750.00 ± 0.00
Statistical analysis
  • Paracetamol Tablet (1000 mg) vs Ibuprofen Capsule (400 mg) · t-test, 2 sided · p = 0.6497 (No multiple comparisons were carried out.) · Ls mean difference: -0.09 · 95% CI -0.49 to 0.31Difference was first named treatment minus second named treatment, such that a positive difference favors the first named treatment.
  • Paracetamol Tablet (1000 mg) vs Ibuprofen Tablet (400 mg) · t-test, 2 sided · p = 0.7591 (No multiple comparisons were carried out.) · Ls mean difference: -0.06 · 95% CI -0.46 to 0.34Difference was first named treatment minus second named treatment, such that a positive difference favors the first named treatment.
  • Paracetamol Tablet (1000 mg) vs Placebo Tablet · t-test, 2 sided · p = 0.4126 (No multiple comparisons were carried out.) · Ls mean difference: 0.17 · 95% CI -0.24 to 0.57Difference was first named treatment minus second named treatment, such that a positive difference favors the first named treatment.
  • Ibuprofen Capsule (400 mg) vs Ibuprofen Tablet (400 mg) · t-test, 2 sided · p = 0.8903 (No multiple comparisons were carried out.) · Ls mean difference: 0.03 · 95% CI -0.39 to 0.45Difference was first named treatment minus second named treatment, such that a positive difference favors the first named treatment.
  • Ibuprofen Capsule (400 mg) vs Placebo Tablet · t-test, 2 sided · p = 0.2227 (No multiple comparisons were carried out.) · Ls mean difference: 0.26 · 95% CI -0.16 to 0.67Difference was first named treatment minus second named treatment, such that a positive difference favors the first named treatment.
  • Ibuprofen Tablet (400 mg) vs Placebo Tablet · t-test, 2 sided · p = 0.2855 (No multiple comparisons were carried out.) · Ls mean difference: 0.23 · 95% CI -0.20 to 0.65Difference was first named treatment minus second named treatment, such that a positive difference favors the first named treatment.
SecondaryIncidence 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
Reported as:
Number · Participants
Incidence of Gastric and/or Duodenal Mucosal Injury
ParticipantsIbuprofen Capsule (400 mg)Ibuprofen Tablet (400 mg)Paracetamol Tablet (1000 mg)Placebo Tablet
Incidence of Gastric and/or Duodenal Mucosal Injury12840
Statistical analysis
  • Ibuprofen Capsule (400 mg) vs Paracetamol Tablet (1000 mg) · Chi-squared · p = 0.0084 (P-value associated with chi-square testing odds ratio.) · Odds ratio (or): 6.19 · 95% CI 1.60 to 23.97Odds Ratio from logistic regression model with treatment as factor and period as covariate.
  • Ibuprofen Tablet (400 mg) vs Paracetamol Tablet (1000 mg) · Chi-squared · p = 0.0999 (P-value associated with chi-square testing odds ratio.) · Odds ratio (or): 3.19 · 95% CI 0.80 to 12.74Odds Ratio from logistic regression model with treatment as factor and period as covariate.
  • Ibuprofen Capsule (400 mg) vs Ibuprofen Tablet (400 mg) · Chi-squared · p = 0.2845 · Odds ratio (or): 1.94 · 95% CI 0.58 to 6.50Odds Ratio from logistic regression model with treatment as factor and period as covariate.
SecondaryIncidence 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
Reported as:
Number · Participants
Incidence of Fecal Occult Blood
ParticipantsParacetamol Tablet (1000 mg)Ibuprofen Capsule (400 mg)Ibuprofen Tablet (400 mg)Placebo Tablet
Score 0 = no fecal occult blood27232222
Score 1 = fecal occult blood present0000

Adverse events

Collected over Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Paracetamol Tablet (1000 mg)—0/28 (0%)4/28 (14.3%)
Ibuprofen Capsule (400 mg)—0/24 (0%)5/24 (20.8%)
Ibuprofen Tablet (400 mg)—1/23 (4.3%)4/23 (17.4%)
Placebo Tablet—0/28 (0%)1/23 (4.3%)
Most frequent serious events
Most frequent serious events
EventParacetamol Tablet (1000 mg)Ibuprofen Capsule (400 mg)Ibuprofen Tablet (400 mg)Placebo Tablet
Breast CancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/280/241/230/28
Most frequent other events
Showing 10 of 12
Most frequent other events
EventParacetamol Tablet (1000 mg)Ibuprofen Capsule (400 mg)Ibuprofen Tablet (400 mg)Placebo Tablet
Abdominal Pain upperGastrointestinal disorders0/283/240/230/23
DiarrheaGastrointestinal disorders1/280/241/230/23
DyspepsiaGastrointestinal disorders0/280/241/231/23
Abdominal Pain LowerGastrointestinal disorders0/280/241/230/23
NauseaGastrointestinal disorders0/280/241/230/23
FlatulenceGastrointestinal disorders0/281/240/230/23
ArthralgiaMusculoskeletal and connective tissue disorders0/281/240/230/23
Back PainMusculoskeletal and connective tissue disorders0/281/240/230/23
Chest PainGeneral disorders0/281/240/230/23
Duodenal UlcerGastrointestinal disorders1/280/240/230/23

Baseline characteristics

Age, Continuous
Age, Continuous(Years)All Randomized Participants
Mean38.1 ± 12.3
Sex: Female, Male
Sex: Female, Male(Participants)All Randomized Participants
Female21
Male7
08

Study locations

1 site
  • Houston Institute for Clinical Research
    Houston, Texas 77074, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 31, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01822665
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Apr 2, 2013
Start date
Feb 2012
Primary completion
Jul 2012
Completion
Jul 2012
Results posted
Mar 31, 2014
Last update
Mar 31, 2014

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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