A Study To Evaluate The Effects Of Celecoxib (Celebrex®) Or Naproxen On Blood Pressure In Pediatric Subjects

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00807846
• Collaborator: (none)
• Enrollment: 201
• Locations: 39
• Arms: 2
• Duration (Months): 39
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This Is A Multicenter, Active-Controlled Trial To Evaluate The Effects Of Celecoxib (Celebrex®) Or Naproxen On Blood Pressure In Pediatric Subjects With Juvenile Idiopathic Arthritis

Condition or Disease	Intervention/Treatment	Phase
Arthritis, Juvenile Rheumatoid	Drug: Celecoxib; Drug: Naproxen	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 201 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 4, 6-week, Randomized Double Blind, Multicenter, Active-controlled Trial To Evaluate The Effects Of Celecoxib (Celebrex) Or Naproxen On Blood Pressure In Pediatric Subjects With Juvenile Idiopathic Arthritis.
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Celecoxib	Drug: Celecoxib; Celecoxib 50 mg or 100 mg PO BID for 6 weeks
Experimental: Naproxen	Drug: Naproxen; Naproxen 7.5 mg/kg PO BID [maximum of 500 mg BID] for 6 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Systolic Blood Pressure (SBP) at Week 6/Final Visit [6 Weeks/Final Visit]

   Value at 6 weeks minus value at baseline.

Secondary Outcome Measures

1. Change From Baseline to Week 2 in SBP. [2 weeks]

   Value at 2 weeks minus value at baseline.

2. Change From Baseline in SBP at Week 4. [4 weeks]

   Value at 4 weeks minus value at baseline.

3. Change From Baseline in Diastolic Blood Pressure (DBP) at Week 2. [2 weeks]

   Value at 2 weeks minus value at baseline.

4. Change From Baseline in DBP at Week 4. [4 weeks]

   Value at 4 weeks minus value at baseline.

5. Change From Baseline in DBP at Week 6/Final Visit [6 weeks]

   Value at 6 weeks/Final Visit minus value at baseline.

6. Change From Baseline in Parent's Assessment of Overall Well-being at Week 6/Final Visit. [6 weeks]

   The parent/legal guardian evaluated the participant's overall well-being at Baseline and at Week 6 (or Final Visit) by placing one vertical line on the visual analog scale (VAS). The VAS ranged from 0 to 100, with 0 being 'very well' and 100 being 'very poor.

7. Number of Participants With >= 30% Improvement in the Parent's Global Assessment of Overall Well-being at Week 6/Final Visit. [Week 6/Final Visit]

   The parent/legal guardian evaluated the participant's overall well-being at Baseline and at Week 6 (or Final Visit) by placing one vertical line on the visual analog scale (VAS). The VAS ranged from 0 to 100, with 0 being 'very well' and 100 being 'very poor.

8. Change From Baseline in Participant's Assessment of Overall Well-being at Week 6/Final Visit. [6 weeks]

   Participants, ≥8 years of age at the baseline, evaluated their own overall well-being at Baseline and at Week 6 (or Final Visit) by placing one vertical line on the VAS. The VAS ranges from 0 to 100, with 0 being 'very well' and 100 being 'very poor'.

9. Number of Participants With >= 30% Improvement in the Participant's Global Assessment of Overall Well-being at Week 6/Final Visit. [Week 6/Final Visit]

   Participants, ≥8 years of age at the baseline, evaluated their own overall well-being at Baseline and at Week 6 (or Final Visit) by placing one vertical line on the VAS. The VAS ranges from 0 to 100, with 0 being 'very well' and 100 being 'very poor'.

Other Outcome Measures

1. Change From Baseline in Assessment of Ambulatory Blood Pressure Monitoring (ABPM) for SBP and DBP at Week 6/Final Visit [6 weeks/Final Visit]

   Ambulatory BP measurements were obtained from 24 participants(in addition to the BP measurements obtained by the cuff technique) participating in the exploratory 24-hour ABPM sub-study. BP was monitored by a 24 hour Ambulatory BP device provided by a central vendor.

2. Change From Baseline in Assessment of ABPM for Heart Rate at Week 6/Final Visit [6 weeks/Final Visit]

   Ambulatory BP measurements were obtained from 24 participants (in addition to the BP measurements obtained by the cuff technique) participating in the exploratory 24-hour ABPM sub-study. A summary of ABPM 24-hour averages for heart rate is presented in this Outcome Measure.

3. Change From Baseline in Assessment of ABPM for SBP and DBP Pressure at Week 6/Final Visit (Sensitivity Analysis Excluding One Participant) [6 weeks/Final Visit]

   A summary of ABPM 24-hour averages for SBP and DBP are presented in this Outcome Measure. One of the participant in the Naproxen ABPM Arm had clinically implausible high BP values at Baseline. Due to the low number of participants in each Arm (12 and 11) these values had a significant impact on the mean baseline values for the Naproxen Arm. As a result, an additional sensitivity analysis was conducted, excluding this participant (Participant ID 10031002).

4. Change From Baseline in Assessment of ABPM for Heart Rate at Week 6/Final Visit (Sensitivity Analysis Excluding One Participant) [6 weeks/Final Visit]

   A summary of ABPM 24-hour averages for heart rate is presented in this Outcome Measure. One of the participant in the Naproxen ABPM Arm had clinically implausible high BP values at Baseline. Due to the low number of participants in each Arm (12 and 11) these values had a significant impact on the mean baseline values for the Naproxen Arm. As a result, an additional sensitivity analysis was conducted, excluding this participant (Participant ID 10031002).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Polyarticular (both rheumatoid factor positive and rheumatoid factor negative),oligoarticular and extended oligoarticular JIA for ≥3 months meeting the International League of Associations for Rheumatology (ILAR) criteria for Juvenile Idiopathic Arthritis (JIA)

• Subjects with Systemic JIA with active arthritis in at least 1 joint but without active systemic features are eligible

• ≥2 years of age and <18 years of age prior to the Baseline visit

• Body weight ≥10 kg at the Baseline visit

• Candidate for chronic NSAID therapy in the Investigator's judgment

Exclusion Criteria:

• Psoriatic arthritis, enthesitis-related arthritis, and undifferentiated arthritis types of JIA

• Active systemic features over the prior 12 weeks in children with systemic Juvenile Idiopathic Arthritis (JIA)

• Subjects with psoriatic arthritis, enthesitis-related arthritis, and undifferentiated arthritis should be excluded

• Subjects with active Systemic JIA should not be enrolled

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Catalina Pointe Clinical Research, Inc.	Tucson	Arizona	United States	85704
2	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
3	Children's Hospital-San Diego	San Diego	California	United States	92123
4	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
5	Children's National Medical Center / Division of Rheumatology	Washington	District of Columbia	United States	20010
6	Arthritis Associates of South Florida	Delray Beach	Florida	United States	33484
7	Delray Research Associates	Delray Beach	Florida	United States	33484
8	Miami Children's Hospital	Miami	Florida	United States	33155-3009
9	Administrative Site-Hawaii Pacific Health Research Institute	Honolulu	Hawaii	United States	96813
10	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
11	Kosair Charities Pediatric Clinical Research Unit - University of Louisville	Louisville	Kentucky	United States	40202
12	Kosair Children's Hospital	Louisville	Kentucky	United States	40202
13	University of Louisville	Louisville	Kentucky	United States	40202
14	University Pediatric Rheumatology of Kentucky	Louisville	Kentucky	United States	40202
15	Children's Hospital and Medical Center	Omaha	Nebraska	United States	68114
16	University of Nebraska Medical Center Pediatric Research Office	Omaha	Nebraska	United States	68198-5456
17	Akron Children's Hospital	Akron	Ohio	United States	44308
18	Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
19	Hospital Roberto del Rio	Santiago	RM	Chile	8380418
20	Hospital Regional de Concepcion Guillermo Grant Benavente	Concepcion	VIII Region	Chile	4070038
21	Instituto de Atencion Pediatrica	San Jose		Costa Rica	00000
22	Clinica San Borja/Centro de Investigacion de Reumatologia	San Borja	Lima	Peru	L41
23	Clinica Ricardo Palma/Sitio de Investigacion de Reumatologia	San Isidro	Lima	Peru	L27
24	Philippine General Hospital	Manila		Philippines	1000
25	University of Santo Tomas Hospital	Manila		Philippines	1008
26	State Healthcare Institution of Moscow "Izmailovskaya City Children's Hospital"	Moscow		Russian Federation	105077
27	First Moscow State Medical University I.M. Sechenov of the Minzdravsocrazvitiya of Russia	Moscow		Russian Federation	119992
28	Smolensk Regional Clinical Hospital	Smolensk		Russian Federation	214000
29	SEIHPE "Smolensk State Medical Academy"of the Minzdravsocrazvitiya of Russia	Smolensk		Russian Federation	214019
30	Institute of Rheumatology	Belgrade		Serbia	11000
31	Children's Clinic of Internal Medicine	Nis		Serbia	18000
32	Clinical Research Unit	Pretoria	Gauteng Province	South Africa	0001
33	CHUV - Unit of Immuno-Allergology and Rhumatology	Ch-1011 Lausanne		Switzerland
34	Universitaets-Kinderspital	Ch-8032 Zuerich		Switzerland
35	Department of Cardioreumatology	Kharkiv		Ukraine	61153
36	Institute of Pediatrics, Obstetrics and Gynecology	Kiev		Ukraine	04050
37	Kyiv City Children Clinical Hospital #1	Kyiv		Ukraine	04209
38	Crimean State Medical University, Chair of Pediatrics with a course of Children Infectious Diseases	Simferopol		Ukraine	95034
39	Zaporizhzhya Regional Clinical Pediatric Hospital	Zaporizhzhya		Ukraine	69063

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: NCT00807846
• Other Study ID Numbers: A3191342
• First Posted: Dec 12, 2008
• 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.: Juvenile Arthritis; Juvenile Rheumatoid Arthritis;Blood Pressure;Juvenile Idiopathic Arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Juvenile; Celecoxib; Naproxen

Study Results

Participant Flow

Recruitment Details	This was a phase 4, 6-week, randomized double-blind, multicenter, active-controlled trial in participants with juvenile idiopathic arthritis (JIA). A total of 221 participants were screened into the study in 32 investigator sites.
Pre-assignment Detail	A total of 101 participants were randomized to treatment with Celecoxib and 100 participants to treatment with Naproxen. Of these randomized, 100 participants received treatment with Celecoxib and 98 participants received treatment with Naproxen. Three participants were randomized but did not receive any treatment.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Period Title: Overall Study
STARTED	100	98
COMPLETED	88	94
NOT COMPLETED	12	4

Baseline Characteristics

Arm/Group Title	Celecoxib	Naproxen	Total
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Total of all reporting groups
Overall Participants	100	98	198
Age, Customized (Number) [Number]
>=2 - <8 Years	22 22%	18 18.4%	40 20.2%
>=8 - <13 Years	34 34%	47 48%	81 40.9%
>=13 - <18 Years	44 44%	33 33.7%	77 38.9%
Sex: Female, Male (Count of Participants)
Female	76 76%	64 65.3%	140 70.7%
Male	24 24%	34 34.7%	58 29.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) at Week 6/Final Visit
Description	Value at 6 weeks minus value at baseline.
Time Frame	6 Weeks/Final Visit

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least one dose of study medication. The Safety Analysis set was used to analyze all BP (blood pressure) measurements. For early terminations the last observation carried forward (LOCF) was used to impute missing data.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	100	98
Least Squares Mean (Standard Error) [mmHg (millimeter of mercury)]	0.366 (0.70)	-0.734 (0.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Celecoxib, Naproxen
	Comments	The primary analysis was based on 90% confidence interval (CI) for the difference across treatment groups (celecoxib - naproxen) in mean change from baseline in SBP. Change from Baseline in BP was analyzed using analysis of covariance (ANCOVA) with model terms for treatment with baseline height, baseline weight, baseline age, and baseline SBP as covariates. No formal hypothesis testing was applied to the primary analysis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.274
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.100
	Confidence Interval	(2-Sided) 90%; -0.56 to 2.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 2 in SBP.
Description	Value at 2 weeks minus value at baseline.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least one dose of study medication. The Safety Analysis set was used to analyze all BP measurements. For early terminations the LOCF was used to impute missing data.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	100	98
Least Squares Mean (Standard Error) [mmHg]	-0.202 (0.53)	-1.290 (0.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Celecoxib, Naproxen
	Comments	For secondary analyses, 95% CIs for the differences across treatment groups (celecoxib - naproxen) in the mean change from baseline were generated. The change from baseline in BP was analyzed using an ANCOVA model with terms for treatment, baseline height, weight, age and baseline BP as covariates. Secondary analyses were conducted using a two-sided test with α=0.05.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.148
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.088
	Confidence Interval	(2-Sided) 95%; -0.39 to 2.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in SBP at Week 4.
Description	Value at 4 weeks minus value at baseline.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least one dose of study medication. The Safety Analysis set was used to analyze all BP measurements. For early terminations the LOCF was used to impute missing data.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	100	98
Least Squares Mean (Standard Error) [mmHg]	-0.170 (0.58)	-2.007 (0.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Celecoxib, Naproxen
	Comments	For secondary analyses, 95% CIs for the differences across treatment groups (celecoxib - naproxen) in the mean change from baseline were generated. The change from baseline in blood pressure was analyzed using an ANCOVA model with terms for treatment, baseline height, weight, age and baseline BP as covariates. Secondary analyses were conducted using a two-sided test with α=0.05.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.837
	Confidence Interval	(2-Sided) 95%; 0.21 to 3.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Diastolic Blood Pressure (DBP) at Week 2.
Description	Value at 2 weeks minus value at baseline.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least one dose of study medication. The Safety Analysis set was used to analyze all BP measurements. For early terminations the LOCF was used to impute missing data.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	100	98
Least Squares Mean (Standard Error) [mmHg]	-1.346 (0.52)	-0.139 (0.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Celecoxib, Naproxen
	Comments	For secondary analyses, 95% CIs for the differences across treatment groups (celecoxib - naproxen) in the mean change from baseline were generated. The change from baseline in BP was analyzed using an ANCOVA model with terms for treatment, baseline height, weight, age and baseline BP as covariates. Secondary analyses were conducted using a two-sided test with α=0.05.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.106
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.207
	Confidence Interval	(2-Sided) 95%; -2.67 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in DBP at Week 4.
Description	Value at 4 weeks minus value at baseline.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least one dose of study medication. The Safety Analysis set was used to analyze all BP measurements. For early terminations the LOCF was used to impute missing data.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	100	98
Least Squares Mean (Standard Error) [mmHg]	-0.628 (0.54)	-0.848 (0.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Celecoxib, Naproxen
	Comments	For secondary analyses, 95% CIs for the differences across treatment groups (celecoxib - naproxen) in the mean change from baseline were generated. The change from baseline in BP was analyzed using an ANCOVA model with terms for treatment, baseline height, weight, age and baseline BP as covariates. Secondary analyses were conducted using a two-sided test with α=0.05.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.776
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.220
	Confidence Interval	(2-Sided) 95%; -1.30 to 1.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in DBP at Week 6/Final Visit
Description	Value at 6 weeks/Final Visit minus value at baseline.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least one dose of study medication. The Safety Analysis set was used to analyze all BP measurements. For early terminations the LOCF was used to impute missing data.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	100	98
Least Squares Mean (Standard Error) [mmHg]	-0.535 (0.54)	-0.356 (0.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Celecoxib, Naproxen
	Comments	For secondary analyses, 95% CIs for the differences across treatment groups (celecoxib - naproxen) in the mean change from baseline were generated. The change from baseline in BP was analyzed using an ANCOVA model with terms for treatment, baseline height, weight, age and baseline blood pressure as covariates. Secondary analyses were conducted using a two-sided test with α=0.05.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.815
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.179
	Confidence Interval	(2-Sided) 95%; -1.69 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Parent's Assessment of Overall Well-being at Week 6/Final Visit.
Description	The parent/legal guardian evaluated the participant's overall well-being at Baseline and at Week 6 (or Final Visit) by placing one vertical line on the visual analog scale (VAS). The VAS ranged from 0 to 100, with 0 being 'very well' and 100 being 'very poor.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Modified-Intent-to-Treat (MITT) Population included all randomized participants who received at least one dose of study medication and had at least one post-baseline efficacy measurement.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	98	98
Least Squares Mean (Standard Error) [mm (millimeter)]	-10.581 (2.081)	-13.614 (2.060)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Celecoxib, Naproxen
	Comments	Change from Baseline to Week 6 was analyzed using ANCOVA model as well with treatment and Baseline value as a covariate. The LS mean change from Baseline was compared between treatment groups and an appropriate p-value and 95% CI for the difference between the two treatment groups was generated. This analysis was conducted using a two-sided test with α=0.05.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.303
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.033
	Confidence Interval	(2-Sided) 95%; -2.76 to 8.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Number of Participants With >= 30% Improvement in the Parent's Global Assessment of Overall Well-being at Week 6/Final Visit.
Description	The parent/legal guardian evaluated the participant's overall well-being at Baseline and at Week 6 (or Final Visit) by placing one vertical line on the visual analog scale (VAS). The VAS ranged from 0 to 100, with 0 being 'very well' and 100 being 'very poor.
Time Frame	Week 6/Final Visit

Outcome Measure Data

Analysis Population Description

The MITT Population included all randomized participants who received at least one dose of study medication and had at least one post-baseline efficacy measurement.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	98	98
Number [Participants]	47 47%	54 55.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Celecoxib, Naproxen
	Comments	The number of subjects with at least a 30% improvement in Parent/Guardian's Global Assessment of Overall Well-Being was compared between the two treatment groups using a chi-square test. A 95% CI for the difference in incidence between groups was also computed.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.392
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.061
	Confidence Interval	(2-Sided) 95%; -0.202 to 0.079
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean Difference (Final Values) indicates difference in incidence (proportion) between treatments.

9. Secondary Outcome

Title	Change From Baseline in Participant's Assessment of Overall Well-being at Week 6/Final Visit.
Description	Participants, ≥8 years of age at the baseline, evaluated their own overall well-being at Baseline and at Week 6 (or Final Visit) by placing one vertical line on the VAS. The VAS ranges from 0 to 100, with 0 being 'very well' and 100 being 'very poor'.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

MITT population was used. Additional 3 participants aged <8 yrs at Baseline in Naproxen Arm provided self-assessments. In Celecoxib Arm, 2 participants (>=8 yrs) not provided self-assessment and 2 (>=8 yrs) provided but they were not from MITT and were excluded; additional 1 participant (<8 yrs) provided self-assessment and included in analysis.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	75	83
Least Squares Mean (Standard Error) [mm]	-12.990 (2.226)	-12.588 (2.115)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Celecoxib, Naproxen
	Comments	Change from Baseline to Week 6 was analyzed using ANCOVA model as well with treatment and Baseline value as a covariate. The LS mean change from Baseline was compared between treatment groups and an appropriate p-value and 95% CI for the difference between the two treatment groups was generated. This analysis was conducted using a two-sided test with α=0.05.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.897
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.402
	Confidence Interval	(2-Sided) 95%; -6.50 to 5.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Number of Participants With >= 30% Improvement in the Participant's Global Assessment of Overall Well-being at Week 6/Final Visit.
Description	Participants, ≥8 years of age at the baseline, evaluated their own overall well-being at Baseline and at Week 6 (or Final Visit) by placing one vertical line on the VAS. The VAS ranges from 0 to 100, with 0 being 'very well' and 100 being 'very poor'.
Time Frame	Week 6/Final Visit

Outcome Measure Data

Analysis Population Description

MITT population was used. Additional 3 participants aged <8 yrs at Baseline in Naproxen Arm provided self-assessments. In Celecoxib Arm, 2 participants (>=8 yrs) not provided self-assessment and 2 (>=8 yrs) provided but they were not from MITT and were excluded; additional 1 participant (<8 yrs) provided self-assessment and included in analysis.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	75	83
Number [Participants]	33 33%	45 45.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Celecoxib, Naproxen
	Comments	The number of participants with at least a 30% improvement in participant's Global Assessment of Overall Well-Being was compared between the two treatment groups using a chi-square test. A 95% CI for the difference in incidence between groups was also computed.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.200
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.102
	Confidence Interval	(2-Sided) 95%; -0.257 to 0.053
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean Difference (Final Values) indicates difference in incidence (proportion) between treatments.

11. Other Pre-specified Outcome

Title	Change From Baseline in Assessment of Ambulatory Blood Pressure Monitoring (ABPM) for SBP and DBP at Week 6/Final Visit
Description	Ambulatory BP measurements were obtained from 24 participants(in addition to the BP measurements obtained by the cuff technique) participating in the exploratory 24-hour ABPM sub-study. BP was monitored by a 24 hour Ambulatory BP device provided by a central vendor.
Time Frame	6 weeks/Final Visit

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least one dose of study medication. For one participant in Naproxen Arm the device failed to collect 11 out of 24 readings at Week 6 and this participant was not included in analysis. ABPM data were analyzed for 12 and 11 participants in Celecoxib and Naproxen Arms respectively.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	12	11
SBP	2.4 (7.02)	-1.7 (12.40)
DBP	0.9 (4.23)	-1.1 (5.36)

12. Other Pre-specified Outcome

Title	Change From Baseline in Assessment of ABPM for Heart Rate at Week 6/Final Visit
Description	Ambulatory BP measurements were obtained from 24 participants (in addition to the BP measurements obtained by the cuff technique) participating in the exploratory 24-hour ABPM sub-study. A summary of ABPM 24-hour averages for heart rate is presented in this Outcome Measure.
Time Frame	6 weeks/Final Visit

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least one dose of study medication. For one participant in Naproxen Arm the device failed to collect 11 out of 24 readings at Week 6 and this participant was not included in analysis. ABPM data were analyzed for 12 and 11 participants in Celecoxib and Naproxen Arms respectively.

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	12	11
Mean (Standard Deviation) [bpm (beats per minute)]	2.5 (6.34)	3.7 (8.50)

13. Other Pre-specified Outcome

Title	Change From Baseline in Assessment of ABPM for SBP and DBP Pressure at Week 6/Final Visit (Sensitivity Analysis Excluding One Participant)
Description	A summary of ABPM 24-hour averages for SBP and DBP are presented in this Outcome Measure. One of the participant in the Naproxen ABPM Arm had clinically implausible high BP values at Baseline. Due to the low number of participants in each Arm (12 and 11) these values had a significant impact on the mean baseline values for the Naproxen Arm. As a result, an additional sensitivity analysis was conducted, excluding this participant (Participant ID 10031002).
Time Frame	6 weeks/Final Visit

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least one dose of study medication. A total of 22 out of 24 participants were analyzed in this sensitivity analysis. Two participants were excluded, one due to outlying BP values at Baseline and another due to the device failure to collect 11 out of 24 readings).

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	12	10
SBP	2.4 (7.02)	1.9 (4.13)
DBP	0.9 (4.23)	0.3 (2.86)

14. Other Pre-specified Outcome

Title	Change From Baseline in Assessment of ABPM for Heart Rate at Week 6/Final Visit (Sensitivity Analysis Excluding One Participant)
Description	A summary of ABPM 24-hour averages for heart rate is presented in this Outcome Measure. One of the participant in the Naproxen ABPM Arm had clinically implausible high BP values at Baseline. Due to the low number of participants in each Arm (12 and 11) these values had a significant impact on the mean baseline values for the Naproxen Arm. As a result, an additional sensitivity analysis was conducted, excluding this participant (Participant ID 10031002).
Time Frame	6 weeks/Final Visit

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least one dose of study medication. A total of 22 out of 24 participants were analyzed in this sensitivity analysis. Two participants were excluded, one due to outlying BP values at Baseline and another due to the device failure to collect 11 out of 24 readings).

Arm/Group Title	Celecoxib	Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Measure Participants	12	10
Mean (Standard Deviation) [bpm]	2.5 (6.34)	3.3 (8.82)

Adverse Events

Time Frame	Up to Week 6/Final Visit
Adverse Event Reporting Description	The same event may appear as both an adverse event (AE) and a serious adverse event (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		Naproxen
Arm/Group Description	Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit		Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
All Cause Mortality
	Celecoxib		Naproxen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Celecoxib		Naproxen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		1/98 (1%)
Injury, poisoning and procedural complications
Hand fracture	0/100 (0%)		1/98 (1%)
Other (Not Including Serious) Adverse Events
	Celecoxib		Naproxen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/100 (10%)		18/98 (18.4%)
Gastrointestinal disorders
Nausea	4/100 (4%)		9/98 (9.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/100 (1%)		5/98 (5.1%)
Nervous system disorders
Headache	7/100 (7%)		4/98 (4.1%)

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.