Trial Outcomes & Findings for Gastrointestinal Safety Evaluation of Two Over the Counter Analgesics (NCT NCT01822665)

Last Updated: 2014-03-31

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

28 participants

Primary outcome timeframe

Day 7

Results posted on

2014-03-31

Participant Flow

Participants were recruited at the clinical site.

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.

Participant milestones

Participant milestones
Measure	Overall Study This was a randomized, 4-way crossover study. Participants received two fast dissolving paracetamol tablets (500 milligrams \[mg\]/tablet) four times daily (QID); two liquid-filled gelatin capsules containing ibuprofen (200 mg/capsule), three times daily (TID); two ibuprofen tablets (200 mg/tablet), TID; and, two fast dissolving placebo tablets QID. All the treatments were administered orally with water. There was a washout period of 7 days following every treatment session.
Overall Study STARTED	28
Overall Study Received Ibuprofen Tablet (400 mg)	23
Overall Study Received Placebo Tablet	23
Overall Study Received Ibuprofen Capsule (400 mg)	24
Overall Study Received Paracetamol Tablet (1000 mg)	28
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Overall Study This was a randomized, 4-way crossover study. Participants received two fast dissolving paracetamol tablets (500 milligrams \[mg\]/tablet) four times daily (QID); two liquid-filled gelatin capsules containing ibuprofen (200 mg/capsule), three times daily (TID); two ibuprofen tablets (200 mg/tablet), TID; and, two fast dissolving placebo tablets QID. All the treatments were administered orally with water. There was a washout period of 7 days following every treatment session.
Overall Study Adverse Event	3
Overall Study Other Reason	5

Baseline Characteristics

Gastrointestinal Safety Evaluation of Two Over the Counter Analgesics

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Randomized Participants n=28 Participants All randomized participants in the study who took at least one treatment dose.
Age, Continuous	38.1 Years STANDARD_DEVIATION 12.3 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Paracetamol Tablet (1000 mg) n=27 Participants Two paracetamol tablets (500 mg/tablet) was administered QID, orally with water.	Ibuprofen Capsule (400 mg) n=23 Participants Two ibuprofen capsules (400 mg/tablet), was administered TID, orally with water.	Ibuprofen Tablet (400 mg) Two ibuprofen capsules (400 mg/tablet), were administered TID, orally with water.	Placebo Tablet Two placebo tablets were administered QID, orally with water.
Gastromucosal Damage (GMD) Score of Paracetamol Tablet vs Ibuprofen Capsule	0.33 Scores on a scale Standard Deviation 0.68	1.48 Scores on a scale Standard Deviation 1.34	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Paracetamol Tablet (1000 mg) n=27 Participants Two paracetamol tablets (500 mg/tablet) was administered QID, orally with water.	Ibuprofen Capsule (400 mg) n=23 Participants Two ibuprofen capsules (400 mg/tablet), was administered TID, orally with water.	Ibuprofen Tablet (400 mg) n=22 Participants Two ibuprofen capsules (400 mg/tablet), were administered TID, orally with water.	Placebo Tablet n=23 Participants Two placebo tablets were administered QID, orally with water.
GMD Scores of Paracetamol Tablet; Ibuprofen Capsule; Ibuprofen Tablet; and Placebo Tablet	0.33 Score on a scale Standard Deviation 0.68	1.48 Score on a scale Standard Deviation 1.34	1.05 Score on a scale Standard Deviation 1.33	0.14 Score on a scale Standard Deviation 0.35

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Paracetamol Tablet (1000 mg) n=27 Participants Two paracetamol tablets (500 mg/tablet) was administered QID, orally with water.	Ibuprofen Capsule (400 mg) n=23 Participants Two ibuprofen capsules (400 mg/tablet), was administered TID, orally with water.	Ibuprofen Tablet (400 mg) n=22 Participants Two ibuprofen capsules (400 mg/tablet), were administered TID, orally with water.	Placebo Tablet n=23 Participants Two placebo tablets were administered QID, orally with water.
Duodenal Mucosal Damage (DMD) Scores	0.15 Score on a scale Standard Deviation 0.77	0.26 Score on a scale Standard Deviation 0.86	0.23 Score on a scale Standard Deviation 0.75	0.00 Score on a scale Standard Deviation 0.00

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Paracetamol Tablet (1000 mg) n=23 Participants Two paracetamol tablets (500 mg/tablet) was administered QID, orally with water.	Ibuprofen Capsule (400 mg) n=22 Participants Two ibuprofen capsules (400 mg/tablet), was administered TID, orally with water.	Ibuprofen Tablet (400 mg) n=27 Participants Two ibuprofen capsules (400 mg/tablet), were administered TID, orally with water.	Placebo Tablet n=23 Participants Two placebo tablets were administered QID, orally with water.
Incidence of Gastric and/or Duodenal Mucosal Injury	12 Participants	8 Participants	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 7

The incidence of fecal occult blood was recorded as a binary response (0 = no presence of blood; 1 = presence of blood).

Outcome measures

Outcome measures
Measure	Paracetamol Tablet (1000 mg) n=27 Participants Two paracetamol tablets (500 mg/tablet) was administered QID, orally with water.	Ibuprofen Capsule (400 mg) n=23 Participants Two ibuprofen capsules (400 mg/tablet), was administered TID, orally with water.	Ibuprofen Tablet (400 mg) n=22 Participants Two ibuprofen capsules (400 mg/tablet), were administered TID, orally with water.	Placebo Tablet n=22 Participants Two placebo tablets were administered QID, orally with water.
Incidence of Fecal Occult Blood Score 1 = fecal occult blood present	0 Participants	0 Participants	0 Participants	0 Participants
Incidence of Fecal Occult Blood Score 0 = no fecal occult blood	27 Participants	23 Participants	22 Participants	22 Participants

Adverse Events

Paracetamol Tablet (1000 mg)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Ibuprofen Capsule (400 mg)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Ibuprofen Tablet (400 mg)

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo Tablet

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Paracetamol Tablet (1000 mg) n=28 participants at risk Two paracetamol tablets (500 mg/tablet) were administered QID, orally with water.	Ibuprofen Capsule (400 mg) n=24 participants at risk Two ibuprofen capsules (400 mg/capsule), were administered TID, orally with water.	Ibuprofen Tablet (400 mg) n=23 participants at risk Two ibuprofen tablets (400 mg/tablet), were administered TID, orally with water.	Placebo Tablet n=23 participants at risk；n=28 participants at risk Two placebo tablets were administered QID, orally with water.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.00% 0/28 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/24 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	4.3% 1/23 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/28 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.

Other adverse events

Other adverse events
Measure	Paracetamol Tablet (1000 mg) n=28 participants at risk Two paracetamol tablets (500 mg/tablet) were administered QID, orally with water.	Ibuprofen Capsule (400 mg) n=24 participants at risk Two ibuprofen capsules (400 mg/capsule), were administered TID, orally with water.	Ibuprofen Tablet (400 mg) n=23 participants at risk Two ibuprofen tablets (400 mg/tablet), were administered TID, orally with water.	Placebo Tablet n=23 participants at risk；n=28 participants at risk Two placebo tablets were administered QID, orally with water.
Gastrointestinal disorders Abdominal Pain upper	0.00% 0/28 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	12.5% 3/24 • Number of events 3 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.
Gastrointestinal disorders Diarrhea	3.6% 1/28 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/24 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	4.3% 1/23 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.
Gastrointestinal disorders Dyspepsia	0.00% 0/28 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/24 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	4.3% 1/23 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	4.3% 1/23 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.
Gastrointestinal disorders Abdominal Pain Lower	0.00% 0/28 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/24 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	4.3% 1/23 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.
Gastrointestinal disorders Duodenal Ulcer	3.6% 1/28 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/24 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.
Gastrointestinal disorders Flatulence	0.00% 0/28 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	4.2% 1/24 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.
Gastrointestinal disorders Gastritis Erosive	3.6% 1/28 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/24 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.
Gastrointestinal disorders Nausea	0.00% 0/28 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/24 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	4.3% 1/23 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/28 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	4.2% 1/24 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/28 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	4.2% 1/24 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.
General disorders Chest Pain	0.00% 0/28 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	4.2% 1/24 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.
Nervous system disorders Somnolence	3.6% 1/28 • Number of events 1 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/24 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.	0.00% 0/23 • Adverse events were collected from the start of the investigational product, and until 5 days following last administration of the investigational product.

Additional Information

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Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
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