Trial Outcomes & Findings for Efficacy Study of PN400 (VIMOVO) Twice Daily and Celebrex Once Daily in Patients With Osteoarthritis (NCT NCT00665431)

Results Overview

Western Ontario and McMaster Universities (WOMAC) pain questionnaire has 5 questions on pain all use visual analog scale (VAS) of 100 mm, with 0 mm being "no pain" and 100 mm being "extreme pain". The outcome measures a change in WOMAC pain at 12 weeks from baseline (in mm). WOMAC is a self-administered, patient-reported health status questionnaire designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. It consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

610 participants

Primary outcome timeframe

Baseline and 12 Weeks

Results posted on

2011-12-06

Participant Flow

Participant milestones

Participant milestones
Measure	(PN 400 (VIMOVO) Twice Daily) PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) placebo (sugar pill) dosed twice daily (bid)
Overall Study STARTED	243	245	122
Overall Study COMPLETED	203	188	98
Overall Study NOT COMPLETED	40	57	24

Reasons for withdrawal

Reasons for withdrawal
Measure	(PN 400 (VIMOVO) Twice Daily) PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) placebo (sugar pill) dosed twice daily (bid)
Overall Study Adverse Event	16	22	6
Overall Study Withdrawal by Subject	17	25	15
Overall Study Lost to Follow-up	3	3	1
Overall Study Other	4	7	2

Baseline Characteristics

Efficacy Study of PN400 (VIMOVO) Twice Daily and Celebrex Once Daily in Patients With Osteoarthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	(PN 400 (VIMOVO) Twice Daily) n=243 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=245 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=122 Participants placebo (sugar pill) dosed twice daily (bid)	Total n=610 Participants Total of all reporting groups
Age Continuous	61.7 years STANDARD_DEVIATION 8.6 • n=5 Participants	62.3 years STANDARD_DEVIATION 8.4 • n=7 Participants	61.6 years STANDARD_DEVIATION 8.7 • n=5 Participants	61.9 years STANDARD_DEVIATION 8.5 • n=4 Participants
Sex: Female, Male Female	158 Participants n=5 Participants	153 Participants n=7 Participants	77 Participants n=5 Participants	388 Participants n=4 Participants
Sex: Female, Male Male	85 Participants n=5 Participants	92 Participants n=7 Participants	45 Participants n=5 Participants	222 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 12 Weeks

Population: Analysis Population: Baseline + took \>= 1 dose + \>= 1 post-baseline WOMAC efficacy evaluation (intent-to-treat population). Used Last Observation Carried Forward

Western Ontario and McMaster Universities (WOMAC) pain questionnaire has 5 questions on pain all use visual analog scale (VAS) of 100 mm, with 0 mm being "no pain" and 100 mm being "extreme pain". The outcome measures a change in WOMAC pain at 12 weeks from baseline (in mm). WOMAC is a self-administered, patient-reported health status questionnaire designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. It consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function).

Outcome measures

Outcome measures
Measure	(PN 400 (VIMOVO) Twice Daily) n=213 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=220 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=106 Participants placebo (sugar pill) dosed twice daily (bid)
Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline	-44.1 mm Standard Deviation 27.5	-43.6 mm Standard Deviation 25.2	-37.3 mm Standard Deviation 26.1

PRIMARY outcome

Timeframe: 12 Weeks

Population: Analysis Population: Baseline + took \>= 1 dose + \>= 1 post-baseline WOMAC efficacy evaluation (intent-to-treat population). Used Last Observation Carried Forward

WOMAC function questionnaire (VAS). The 17 questions about function all use visual analog scale (VAS) of 100 mm; 0 mm being "no pain" and 100 mm being "extreme pain". The outcome measures a change in WOMAC pain from baseline (in mm). The Western Ontario and McMaster Universities (WOMAC) is a self-administered, patient-reported health status questionnaire that is designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. The index consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function).

Outcome measures

Outcome measures
Measure	(PN 400 (VIMOVO) Twice Daily) n=213 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=220 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=106 Participants placebo (sugar pill) dosed twice daily (bid)
Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline	-38.7 mm Standard Deviation 27.2	-37.7 mm Standard Deviation 27.5	-30.9 mm Standard Deviation 28

PRIMARY outcome

Timeframe: 12 Weeks

Population: Analysis Population: Baseline + took \>= 1 dose + \>= 1 post-baseline PGA efficacy evaluation (intent-to-treat population). Used Last Observation Carried Forward

PGA questionnaire. The patient global assessment (PGA) question asks about how the subject is doing considering his/her arthritis and is measured by a visual analog scale (VAS); 0 mm (very poor) 100 mm (excellent). The outcome measures a change from baseline PGA in mm.

Outcome measures

Outcome measures
Measure	(PN 400 (VIMOVO) Twice Daily) n=235 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=234 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=115 Participants placebo (sugar pill) dosed twice daily (bid)
Change in Patient Global Assessment (PGA) Subscore From Baseline	27.7 mm Standard Deviation 34.8	26.4 mm Standard Deviation 30.3	22.4 mm Standard Deviation 31.3

SECONDARY outcome

Timeframe: Baseline and Day 7

Population: Intent to treat

For APS-POQ score is the change from Baseline scores calculated for each subject through Day 7. Scale 0 through 70, where 0=no pain interference and 70=complete interference.

Outcome measures

Outcome measures
Measure	(PN 400 (VIMOVO) Twice Daily) n=236 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=237 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=120 Participants placebo (sugar pill) dosed twice daily (bid)
Mean Change From Baseline in American Pain Society Patient Outcome Questionnaire (APS-POQ)Total Interference Caused by Pain.	-18.8 Units on a scale Standard Deviation 15.8	-16.6 Units on a scale Standard Deviation 14.8	-11.6 Units on a scale Standard Deviation 12.3

SECONDARY outcome

Timeframe: Week 6

Population: Intent to treat

Western Ontario and McMaster Universities (WOMAC) pain questionnaire has 5 questions on pain all use visual analog scale (VAS) of 100 mm, with 0 mm being "no pain" and 100 mm being "extreme pain". The outcome measures a change in WOMAC pain at 6 weeks from baseline (in mm). WOMAC is a self-administered, patient-reported health status questionnaire designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. It consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function).

Outcome measures

Outcome measures
Measure	(PN 400 (VIMOVO) Twice Daily) n=188 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=197 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=96 Participants placebo (sugar pill) dosed twice daily (bid)
Change in Western Ontario and McMaster Universities (WOMAC) Pain Questionnaire Subscore From Baseline	-44.3 mm Standard Deviation 25.7	-39.6 mm Standard Deviation 25.7	-33.9 mm Standard Deviation 25.4

SECONDARY outcome

Timeframe: Week 6

Population: Intent to treat

WOMAC function questionnaire (VAS). The 17 questions about function all use visual analog scale (VAS) of 100 mm; 0 mm being "no pain" and 100 mm being "extreme pain". The outcome measures a change in WOMAC pain from baseline (in mm). The Western Ontario and McMaster Universities (WOMAC) is a self-administered, patient-reported health status questionnaire that is designed to capture elements of pain, stiffness and physical disability in patients with OA of the knee and/or hip joints. The index consists of 24 questions (5 questions about pain, 2 on stiffness and 17 about physical function).

Outcome measures

Outcome measures
Measure	(PN 400 (VIMOVO) Twice Daily) n=188 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=197 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=96 Participants placebo (sugar pill) dosed twice daily (bid)
Change in Western Ontario and McMaster Universities (WOMAC) Function Questionnaire Subscore From Baseline	-38.5 mm Standard Deviation 26.2	-34.6 mm Standard Deviation 26.3	-29.0 mm Standard Deviation 26.4

SECONDARY outcome

Timeframe: Week 6

Population: Intent to treat

PGA questionnaire. The patient global assessment (PGA) question asks about how the subject is doing considering his/her arthritis and is measured by a visual analog scale (VAS); 0 mm (very poor) 100 mm (excellent). The outcome measures a change from baseline PGA in mm.

Outcome measures

Outcome measures
Measure	(PN 400 (VIMOVO) Twice Daily) n=233 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=233 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=114 Participants placebo (sugar pill) dosed twice daily (bid)
Change in Patient Global Assessment (PGA) Subscore From Baseline	25.9 mm Standard Deviation 34.5	24.4 mm Standard Deviation 29.3	22.3 mm Standard Deviation 29.9

SECONDARY outcome

Timeframe: 12 weeks

Population: Intent to treat

Tablet pill count

Outcome measures

Outcome measures
Measure	(PN 400 (VIMOVO) Twice Daily) n=235 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=234 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=116 Participants placebo (sugar pill) dosed twice daily (bid)
Antacid Tablet Use	13.4 Tablets per subject Standard Deviation 31.3	20.9 Tablets per subject Standard Deviation 66	27.3 Tablets per subject Standard Deviation 86.9

SECONDARY outcome

Timeframe: 12 weeks

Population: intent to treat with last observation carried forward

Change from Baseline in the Modified Severity of Dyspepsia Assessment (mSODA) average daily pain intensity converted total score at Week 12. The mSODA instruments consists of 6 questions about abdominal discomfort during the past 24 hours, with a converted score of 2 through 47. Lower score equals less pain.

Outcome measures

Outcome measures
Measure	(PN 400 (VIMOVO) Twice Daily) n=238 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=241 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=120 Participants placebo (sugar pill) dosed twice daily (bid)
Modified Severity of Dyspepsia Assessment (mSODA)	-4.5 Scores on a scale Standard Deviation 10.0	-3.3 Scores on a scale Standard Deviation 9.0	-3.5 Scores on a scale Standard Deviation 9.8

SECONDARY outcome

Timeframe: 12 weeks

Population: Intent to treat

During 12 weeks, daily heartburn question with ratings none, mild, moderate, or severe. Percent of days with Heartburn resolution (heartburn is none).

Outcome measures

Outcome measures
Measure	(PN 400 (VIMOVO) Twice Daily) n=241 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=243 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=122 Participants placebo (sugar pill) dosed twice daily (bid)
Percent of Days With no Heartburn (Heartburn Resolution)	78.4 percent days Standard Deviation 34.5	72.1 percent days Standard Deviation 35.8	71.1 percent days Standard Deviation 39.0

SECONDARY outcome

Timeframe: daily during 12 weeks

Population: Safety population

Number of participants reporting pre-specified non-steroidal antiinflammatory drug-associated (NSAID) upper gastrointestinal (UGI) symptoms. Pre-specified NSAID-associated UGI symptoms include adverse events such as dyspepsia, abdominal pain or discomfort, nausea, vomiting.

Outcome measures

Outcome measures
Measure	(PN 400 (VIMOVO) Twice Daily) n=243 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=245 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=122 Participants placebo (sugar pill) dosed twice daily (bid)
Number of Participants Reporting Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal (UGI) Symptoms	46 participants	53 participants	25 participants

SECONDARY outcome

Timeframe: daily during 12 weeks

Population: Safety population

The number of subjects who discontinued from the study due to any pre-specified non-steroidal antiinflammatory drug (NSAID)-associated upper gastrointestinal (UGI) adverse event (as classified by MedDRA). Pre-specified NSAID-associated UGI symptoms include adverse events such as dyspepsia, abdominal pain or discomfort, nausea, vomiting.

Outcome measures

Outcome measures
Measure	(PN 400 (VIMOVO) Twice Daily) n=243 Participants PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=245 Participants Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=122 Participants placebo (sugar pill) dosed twice daily (bid)
The Number of Subjects Who Discontinued From the Study Due to Any Pre-specified Non-steroidal Antiinflammatory Drug-associated Upper Gastrointestinal Adverse Event	2 participants	9 participants	3 participants

Adverse Events

(PN 400 (VIMOVO) Twice Daily)

Serious events: 3 serious events

Other events: 111 other events

Deaths: 0 deaths

(Celebrex 200 mg Once Daily)

Serious events: 3 serious events

Other events: 107 other events

Deaths: 0 deaths

(Placebo Twice Daily)

Serious events: 1 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	(PN 400 (VIMOVO) Twice Daily) n=243 participants at risk PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=245 participants at risk Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=122 participants at risk placebo (sugar pill) dosed twice daily (bid)
Cardiac disorders Coronary artery disease	0.00% 0/243 • randomization - 28 days post last dose	0.41% 1/245 • Number of events 1 • randomization - 28 days post last dose	0.00% 0/122 • randomization - 28 days post last dose
Cardiac disorders Atrial flutter	0.41% 1/243 • Number of events 1 • randomization - 28 days post last dose	0.00% 0/245 • randomization - 28 days post last dose	0.00% 0/122 • randomization - 28 days post last dose
General disorders Chest pain	0.41% 1/243 • Number of events 1 • randomization - 28 days post last dose	0.00% 0/245 • randomization - 28 days post last dose	0.00% 0/122 • randomization - 28 days post last dose
Injury, poisoning and procedural complications Hip fracture	0.41% 1/243 • Number of events 1 • randomization - 28 days post last dose	0.00% 0/245 • randomization - 28 days post last dose	0.00% 0/122 • randomization - 28 days post last dose
Immune system disorders Drug hypersensitivity	0.00% 0/243 • randomization - 28 days post last dose	0.41% 1/245 • Number of events 1 • randomization - 28 days post last dose	0.00% 0/122 • randomization - 28 days post last dose
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/243 • randomization - 28 days post last dose	0.41% 1/245 • Number of events 1 • randomization - 28 days post last dose	0.00% 0/122 • randomization - 28 days post last dose
Nervous system disorders Intracranial aneurism	0.00% 0/243 • randomization - 28 days post last dose	0.00% 0/245 • randomization - 28 days post last dose	0.82% 1/122 • Number of events 1 • randomization - 28 days post last dose

Other adverse events

Additional Information

Sr VP Clinical Research

Pozen

Phone: 919 913 1030

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	(PN 400 (VIMOVO) Twice Daily) n=243 participants at risk PN 400: 500 mg naproxen/20 mg esomeprazole	(Celebrex 200 mg Once Daily) n=245 participants at risk Celecoxib 200 mg (Celebrex) taken once daily	(Placebo Twice Daily) n=122 participants at risk placebo (sugar pill) dosed twice daily (bid)
Gastrointestinal disorders Dyspepsia	11.5% 28/243 • Number of events 28 • randomization - 28 days post last dose	13.5% 33/245 • Number of events 33 • randomization - 28 days post last dose	13.1% 16/122 • Number of events 16 • randomization - 28 days post last dose
Gastrointestinal disorders Diarrhea	4.9% 12/243 • Number of events 12 • randomization - 28 days post last dose	2.4% 6/245 • Number of events 6 • randomization - 28 days post last dose	4.9% 6/122 • Number of events 6 • randomization - 28 days post last dose
Gastrointestinal disorders Abdominal pain upper	4.1% 10/243 • Number of events 10 • randomization - 28 days post last dose	4.9% 12/245 • Number of events 12 • randomization - 28 days post last dose	4.9% 6/122 • Number of events 6 • randomization - 28 days post last dose
Gastrointestinal disorders Constipation	3.3% 8/243 • Number of events 8 • randomization - 28 days post last dose	2.0% 5/245 • Number of events 5 • randomization - 28 days post last dose	0.82% 1/122 • Number of events 1 • randomization - 28 days post last dose
Gastrointestinal disorders Nausea	2.1% 5/243 • Number of events 5 • randomization - 28 days post last dose	3.7% 9/245 • Number of events 9 • randomization - 28 days post last dose	2.5% 3/122 • Number of events 3 • randomization - 28 days post last dose
Infections and infestations Upper respiratory tract infection	2.9% 7/243 • Number of events 7 • randomization - 28 days post last dose	0.82% 2/245 • Number of events 2 • randomization - 28 days post last dose	1.6% 2/122 • Number of events 2 • randomization - 28 days post last dose
Infections and infestations Urinary tract infection	2.1% 5/243 • Number of events 5 • randomization - 28 days post last dose	0.82% 2/245 • Number of events 2 • randomization - 28 days post last dose	0.82% 1/122 • Number of events 1 • randomization - 28 days post last dose
Musculoskeletal and connective tissue disorders Joint swelling	2.1% 5/243 • Number of events 5 • randomization - 28 days post last dose	1.2% 3/245 • Number of events 3 • randomization - 28 days post last dose	0.00% 0/122 • randomization - 28 days post last dose
Musculoskeletal and connective tissue disorders Back pain	1.6% 4/243 • Number of events 4 • randomization - 28 days post last dose	3.7% 9/245 • Number of events 9 • randomization - 28 days post last dose	0.82% 1/122 • Number of events 1 • randomization - 28 days post last dose
Musculoskeletal and connective tissue disorders Arthralgia	0.82% 2/243 • Number of events 2 • randomization - 28 days post last dose	3.7% 9/245 • Number of events 9 • randomization - 28 days post last dose	0.82% 1/122 • Number of events 1 • randomization - 28 days post last dose
Nervous system disorders Dizziness	3.3% 8/243 • Number of events 8 • randomization - 28 days post last dose	0.82% 2/245 • Number of events 2 • randomization - 28 days post last dose	0.82% 1/122 • Number of events 1 • randomization - 28 days post last dose
Nervous system disorders Headache	2.5% 6/243 • Number of events 6 • randomization - 28 days post last dose	3.3% 8/245 • Number of events 8 • randomization - 28 days post last dose	6.6% 8/122 • Number of events 8 • randomization - 28 days post last dose
Respiratory, thoracic and mediastinal disorders Cough	2.1% 5/243 • Number of events 5 • randomization - 28 days post last dose	0.82% 2/245 • Number of events 2 • randomization - 28 days post last dose	1.6% 2/122 • Number of events 2 • randomization - 28 days post last dose
General disorders Edema periphera	2.5% 6/243 • Number of events 6 • randomization - 28 days post last dose	1.2% 3/245 • Number of events 3 • randomization - 28 days post last dose	1.6% 2/122 • Number of events 2 • randomization - 28 days post last dose
General disorders Pyrexia	0.00% 0/243 • randomization - 28 days post last dose	0.82% 2/245 • Number of events 2 • randomization - 28 days post last dose	2.5% 3/122 • Number of events 3 • randomization - 28 days post last dose