Study Of Celecoxib In Healthy Subjects

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00994461
• Collaborator: (none)
• Enrollment: 190
• Locations: 3
• Arms: 3
• Duration (Months): 5
• Patients Per Site: 63.3
• Patients Per Site Per Month: 12.8

Study Details

Study Description

Brief Summary

A study to confirm the superiority of celecoxib 100 mg BID to loxoprofen 60 mg TID in the incidence of gastroduodenal endoscopic ulcers after 2 weeks treatment.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Celecoxib; Drug: Loxoprofen; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 190 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-Controlled, Double-Blind, Phase 4 Study To Compare The Effect Of Celecoxib 100 Mg BID, Loxoprofen 60 Mg TID And Placebo On The Gastroduodenal Mucosa In Healthy Subjects
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Celecoxib	Drug: Celecoxib; Celecoxib 100mg tablet twice a day with meal for 2 weeks
Active Comparator: Loxoprofen	Drug: Loxoprofen; Loxoprofen 60mg tablet three times a day with meal for 2 weeks
Placebo Comparator: Placebo	Drug: Placebo; Placebo tablet three times a day with meal for 2 weeks

Outcome Measures

Primary Outcome Measures

1. Incidence of Gastroduodenal Ulcers [2 weeks]

   The percentage of subjects who had gastroduodenal endoscopic ulcers after 2 weeks treatment (The number of subjects who had gastroduodenal endoscopic ulcers after 2 weeks treatment divided by participants multiplied by 100.) An ulcer is defined as any break in the mucosa at least 3 mm in diameter with unequivocal depth.

Secondary Outcome Measures

1. Incidence of Any Gastric, and Duodenal Ulcers [2 weeks]

   The percentage of subjects who had gastric and duodenal endoscopic ulcers after 2 weeks treatment (The number of subjects who had gastric and duodenal endoscopic ulcers after 2 weeks treatment divided by participants multiplied by 100.) An ulcer is defined as any break in the mucosa at least 3 mm in diameter with unequivocal depth.

2. Incidence of Any Gastroduodenal, Gastric, and Duodenal Ulcers and/or Erosions [2 weeks]

   The percentage of subjects who had gastroduodenal, gastric, and duodenal endoscopic ulcers and/or erosions after 2 weeks treatment (The number of subjects who had gastroduodenal, gastric, and duodenal endoscopic ulcers and/or erosions after 2 weeks treatment divided by participants multiplied by 100.) An ulcer is defined as any break in the mucosa at least 3 mm in diameter with unequivocal depth. An erosion is defined as a lesion producing a definite break in the mucosa with equivocal depth.

3. Post-treatment Gastroduodenal Endoscopic Scores (According to Mucosal Grading Scale) [2 weeks]

   Number of subjects for each gastroduodenal endoscopic score (according to Mucosal Grading Scale) after 2 weeks treatment (Score 0 = normal mucosa (no visible lesions); Score 1 = 1 to 10 petechiae; Score 2 = more than 10 petechiae; Score 3 = 1 to 5 erosions; Score 4 = 6 to 10 erosions; Score 5 = 11 to 25 erosions; Score 6 = more than 25 erosions; Score 7 = ulcer)

4. Number of Gastroduodenal Ulcers in Each Subject [2 weeks]

   Number of subjects for each number of gastroduodenal endoscopic ulcers after 2 weeks treatment (An ulcer is defined as any break in the mucosa at least 3 mm in diameter with unequivocal depth.)

5. Number of Gastroduodenal Erosions in Each Subject [2 weeks]

   Number of subjects for each number of gastroduodenal endoscopic erosions after 2 weeks treatment (An erosion is defined as a lesion producing a definite break in the mucosa with equivocal depth.)

6. Incidence of Treatment-emergent, All-causality GI Body System Adverse Events [2 weeks]

   The percentage of subjects who had treatment-emergent, all-causality gastrointestinal body system adverse events after 2 weeks treatment (The number of subjects who had treatment-emergent, all-causality gastrointestinal body system adverse events after 2 weeks treatment divided by participants multiplied by 100.)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy Volunteers

Exclusion Criteria:

• Endoscopic evidence of ulceration, erosion or active bleeding etc. in the esophagus, stomach, pylorus and/or duodenum prior to treatment endoscopy

• A history of gastrointestinal ulcer

• Any use of celecoxib, nonsteroidal anti-inflammatory drugs (including aspirin), anti-ulcer medication, antacids, systemic steroids or antibiotics within four weeks prior to the first dose of study medication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Yokohama	Kanagawa	Japan
2	Pfizer Investigational Site	Minato-ku	Tokyo	Japan
3	Pfizer Investigational Site	Shinjuku-ku	Tokyo	Japan

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT00994461
• Other Study ID Numbers: A3191345
• First Posted: Oct 14, 2009
• Last Update Posted: Feb 2, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: Endoscopy
• Additional relevant MeSH terms: Celecoxib; Loxoprofen

Study Results

Participant Flow

Recruitment Details	Subjects were screened at 3 centers in Japan.

Arm/Group Title	Celecoxib	Loxoprofen	Placebo
Arm/Group Description	Celecoxib 100 mg tablet twice a day with meal for 2 weeks	Loxoprofen 60 mg tablet three times a day with meal for 2 weeks	Placebo tablet three times a day with meal for 2 weeks
Period Title: Overall Study
STARTED	76	76	37
COMPLETED	74	75	37
NOT COMPLETED	2	1	0

Baseline Characteristics

Arm/Group Title	Celecoxib	Loxoprofen	Placebo	Total
Arm/Group Description	Celecoxib 100 mg tablet twice a day with meal for 2 weeks	Loxoprofen 60 mg tablet three times a day with meal for 2 weeks	Placebo tablet three times a day with meal for 2 weeks	Total of all reporting groups
Overall Participants	76	76	37	189
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.5 (9.65)	57.8 (9.38)	59.1 (9.18)	57.5 (9.45)
Sex: Female, Male (Count of Participants)
Female	54 71.1%	55 72.4%	26 70.3%	135 71.4%
Male	22 28.9%	21 27.6%	11 29.7%	54 28.6%
Helicobacter pylori (H. pylori) status (Number) [Number]
Positive	32 42.1%	33 43.4%	16 43.2%	81 42.9%
Negative	44 57.9%	43 56.6%	21 56.8%	108 57.1%

Outcome Measures

1. Primary Outcome

Title	Incidence of Gastroduodenal Ulcers
Description	The percentage of subjects who had gastroduodenal endoscopic ulcers after 2 weeks treatment (The number of subjects who had gastroduodenal endoscopic ulcers after 2 weeks treatment divided by participants multiplied by 100.) An ulcer is defined as any break in the mucosa at least 3 mm in diameter with unequivocal depth.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

The modified-safety analysis set (m-SAF) consisted of all randomized subjects who received at least one dose of the study drug, and underwent endoscopy at baseline and at the end/discontinuation of treatment, as well.

Arm/Group Title	Celecoxib	Loxoprofen	Placebo
Arm/Group Description	Celecoxib 100 mg tablet twice a day with meal for 2 weeks	Loxoprofen 60 mg tablet three times a day with meal for 2 weeks	Placebo tablet three times a day with meal for 2 weeks
Measure Participants	74	76	37
Number [Percent]	1.4	27.6	2.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Celecoxib, Loxoprofen
	Comments	Hypothesis testing was conducted with significant p-value level of under 0.05.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Cochran-Mantel-Haenszel (CMH) test stratified by H. pylori status was employed for the comparison of celecoxib and loxoprofen with placebo. The multiplicity of test was not adjusted because these comparisons were for the secondary objective.
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by H. pylori status was employed. Continuous correction was used.

2. Secondary Outcome

Title	Incidence of Any Gastric, and Duodenal Ulcers
Description	The percentage of subjects who had gastric and duodenal endoscopic ulcers after 2 weeks treatment (The number of subjects who had gastric and duodenal endoscopic ulcers after 2 weeks treatment divided by participants multiplied by 100.) An ulcer is defined as any break in the mucosa at least 3 mm in diameter with unequivocal depth.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

The m-SAF consisted of all randomized subjects who received at least one dose of the study drug, and underwent endoscopy at baseline and at the end/discontinuation of treatment, as well.

Arm/Group Title	Celecoxib	Loxoprofen	Placebo
Arm/Group Description	Celecoxib 100 mg tablet twice a day with meal for 2 weeks	Loxoprofen 60 mg tablet three times a day with meal for 2 weeks	Placebo tablet three times a day with meal for 2 weeks
Measure Participants	74	76	37
Gastric ulcers	0	25.0	2.7
Duodenal ulcers	1.4	5.3	0

3. Secondary Outcome

Title	Incidence of Any Gastroduodenal, Gastric, and Duodenal Ulcers and/or Erosions
Description	The percentage of subjects who had gastroduodenal, gastric, and duodenal endoscopic ulcers and/or erosions after 2 weeks treatment (The number of subjects who had gastroduodenal, gastric, and duodenal endoscopic ulcers and/or erosions after 2 weeks treatment divided by participants multiplied by 100.) An ulcer is defined as any break in the mucosa at least 3 mm in diameter with unequivocal depth. An erosion is defined as a lesion producing a definite break in the mucosa with equivocal depth.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

The m-SAF consisted of all randomized subjects who received at least one dose of the study drug, and underwent endoscopy at baseline and at the end/discontinuation of treatment, as well.

Arm/Group Title	Celecoxib	Loxoprofen	Placebo
Arm/Group Description	Celecoxib 100 mg tablet twice a day with meal for 2 weeks	Loxoprofen 60 mg tablet three times a day with meal for 2 weeks	Placebo tablet three times a day with meal for 2 weeks
Measure Participants	74	76	37
Gastroduodenal ulcers and/or erosions	36.5	53.9	24.3
Gastric ulcers and/or erosions	35.1	53.9	24.3
Duodenal ulcers and/or erosions	4.1	5.3	0

4. Secondary Outcome

Title	Post-treatment Gastroduodenal Endoscopic Scores (According to Mucosal Grading Scale)
Description	Number of subjects for each gastroduodenal endoscopic score (according to Mucosal Grading Scale) after 2 weeks treatment (Score 0 = normal mucosa (no visible lesions); Score 1 = 1 to 10 petechiae; Score 2 = more than 10 petechiae; Score 3 = 1 to 5 erosions; Score 4 = 6 to 10 erosions; Score 5 = 11 to 25 erosions; Score 6 = more than 25 erosions; Score 7 = ulcer)
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

The m-SAF consisted of all randomized subjects who received at least one dose of the study drug, and underwent endoscopy at baseline and at the end/discontinuation of treatment, as well.

Arm/Group Title	Celecoxib	Loxoprofen	Placebo
Arm/Group Description	Celecoxib 100 mg tablet twice a day with meal for 2 weeks	Loxoprofen 60 mg tablet three times a day with meal for 2 weeks	Placebo tablet three times a day with meal for 2 weeks
Measure Participants	74	76	37
Score 0	38 50%	33 43.4%	22 59.5%
Score 1	8 10.5%	2 2.6%	6 16.2%
Score 2	1 1.3%	0 0%	0 0%
Score 3	22 28.9%	19 25%	8 21.6%
Score 4	4 5.3%	1 1.3%	0 0%
Score 5	0 0%	0 0%	0 0%
Score 6	0 0%	0 0%	0 0%
Score 7	1 1.3%	21 27.6%	1 2.7%

5. Secondary Outcome

Title	Number of Gastroduodenal Ulcers in Each Subject
Description	Number of subjects for each number of gastroduodenal endoscopic ulcers after 2 weeks treatment (An ulcer is defined as any break in the mucosa at least 3 mm in diameter with unequivocal depth.)
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

The m-SAF consisted of all randomized subjects who received at least one dose of the study drug, and underwent endoscopy at baseline and at the end/discontinuation of treatment, as well.

Arm/Group Title	Celecoxib	Loxoprofen	Placebo
Arm/Group Description	Celecoxib 100 mg tablet twice a day with meal for 2 weeks	Loxoprofen 60 mg tablet three times a day with meal for 2 weeks	Placebo tablet three times a day with meal for 2 weeks
Measure Participants	74	76	37
0 ulcer	73 96.1%	55 72.4%	36 97.3%
1 ulcer	1 1.3%	10 13.2%	1 2.7%
2 ulcers	0 0%	5 6.6%	0 0%
3 ulcers	0 0%	2 2.6%	0 0%
4 ulcers	0 0%	0 0%	0 0%
5 ulcers	0 0%	0 0%	0 0%
6 ulcers	0 0%	1 1.3%	0 0%
7 ulcers	0 0%	2 2.6%	0 0%
8 ulcers	0 0%	1 1.3%	0 0%
9 ulcers	0 0%	0 0%	0 0%
10 or more ulcers	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Number of Gastroduodenal Erosions in Each Subject
Description	Number of subjects for each number of gastroduodenal endoscopic erosions after 2 weeks treatment (An erosion is defined as a lesion producing a definite break in the mucosa with equivocal depth.)
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

The m-SAF consisted of all randomized subjects who received at least one dose of the study drug, and underwent endoscopy at baseline and at the end/discontinuation of treatment, as well.

Arm/Group Title	Celecoxib	Loxoprofen	Placebo
Arm/Group Description	Celecoxib 100 mg tablet twice a day with meal for 2 weeks	Loxoprofen 60 mg tablet three times a day with meal for 2 weeks	Placebo tablet three times a day with meal for 2 weeks
Measure Participants	74	76	37
0 erosion	47 61.8%	41 53.9%	29 78.4%
1 erosion	14 18.4%	13 17.1%	5 13.5%
2 erosions	4 5.3%	3 3.9%	1 2.7%
3 erosions	5 6.6%	9 11.8%	2 5.4%
4 erosions	0 0%	4 5.3%	0 0%
5 erosions	0 0%	3 3.9%	0 0%
6 erosions	2 2.6%	1 1.3%	0 0%
7 erosions	1 1.3%	1 1.3%	0 0%
8 erosions	0 0%	1 1.3%	0 0%
9 erosions	0 0%	0 0%	0 0%
10 or more erosions	1 1.3%	0 0%	0 0%

7. Secondary Outcome

Title	Incidence of Treatment-emergent, All-causality GI Body System Adverse Events
Description	The percentage of subjects who had treatment-emergent, all-causality gastrointestinal body system adverse events after 2 weeks treatment (The number of subjects who had treatment-emergent, all-causality gastrointestinal body system adverse events after 2 weeks treatment divided by participants multiplied by 100.)
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

The m-SAF consisted of all randomized subjects who received at least one dose of the study drug, and underwent endoscopy at baseline and at the end/discontinuation of treatment, as well.

Arm/Group Title	Celecoxib	Loxoprofen	Placebo
Arm/Group Description	Celecoxib 100 mg tablet twice a day with meal for 2 weeks	Loxoprofen 60 mg tablet three times a day with meal for 2 weeks	Placebo tablet three times a day with meal for 2 weeks
Measure Participants	74	76	37
Number [Percent]	24.3	47.4	16.2

Adverse Events

Time Frame	2 weeks
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Celecoxib		Loxoprofen		Placebo
Arm/Group Description	Celecoxib 100 mg tablet twice a day with meal for 2 weeks		Loxoprofen 60 mg tablet three times a day with meal for 2 weeks		Placebo tablet three times a day with meal for 2 weeks
All Cause Mortality
	Celecoxib		Loxoprofen		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Celecoxib		Loxoprofen		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/76 (0%)		0/76 (0%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	Celecoxib		Loxoprofen		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/76 (25%)		37/76 (48.7%)		8/37 (21.6%)
Gastrointestinal disorders
Abdominal discomfort	2/76 (2.6%)		4/76 (5.3%)		0/37 (0%)
Abdominal distension	0/76 (0%)		3/76 (3.9%)		0/37 (0%)
Abdominal pain upper	2/76 (2.6%)		1/76 (1.3%)		0/37 (0%)
Constipation	0/76 (0%)		2/76 (2.6%)		0/37 (0%)
Diarrhoea	1/76 (1.3%)		2/76 (2.6%)		2/37 (5.4%)
Duodenitis	0/76 (0%)		2/76 (2.6%)		0/37 (0%)
Dyspepsia	1/76 (1.3%)		0/76 (0%)		1/37 (2.7%)
Epigastric discomfort	1/76 (1.3%)		2/76 (2.6%)		0/37 (0%)
Erosive duodenitis	1/76 (1.3%)		5/76 (6.6%)		0/37 (0%)
Gastric ulcer	0/76 (0%)		4/76 (5.3%)		0/37 (0%)
Gastritis	2/76 (2.6%)		1/76 (1.3%)		0/37 (0%)
Gastritis erosive	8/76 (10.5%)		28/76 (36.8%)		3/37 (8.1%)
Oesophagitis	0/76 (0%)		0/76 (0%)		1/37 (2.7%)
Stomatitis	2/76 (2.6%)		0/76 (0%)		0/37 (0%)
Investigations
Alanine aminotransferase increased	1/76 (1.3%)		2/76 (2.6%)		0/37 (0%)
Bilirubin conjugated increased	0/76 (0%)		0/76 (0%)		1/37 (2.7%)
Blood bilirubin increased	0/76 (0%)		0/76 (0%)		1/37 (2.7%)
Musculoskeletal and connective tissue disorders
Back pain	0/76 (0%)		0/76 (0%)		1/37 (2.7%)
Nervous system disorders
Somnolence	1/76 (1.3%)		4/76 (5.3%)		0/37 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.