A fixed-dose combination of naproxen and esomeprazole magnesium has comparable upper gastrointestinal tolerability to celecoxib in patients with osteoarthritis of the knee: Results from two randomized, parallel-group, placebo-controlled trials

Figures & data

Figure 1. Study disposition. (AE = adverse event; CEL = celecoxib; mITT = modified intent-to-treat; NAP/ESO = naproxen/esomeprazole magnesium; PBO = placebo; PP = per protocol.) Hochberg et al, Curr Med Res Opin, 2011; 27: 1243-53, copyright © 2011, Informa Healthcare. Reproduced with permission of Informa Healthcare.

Table I. Patient demographics and baseline characteristics.

	Study 307			Study 309
	NAP/ESO (n = 246)	CEL (n = 242)	PBO (n = 124)	NAP/ESO (n = 241)	CEL (n = 244)	PBO (n = 122)
Gender, n (%)
Female	161 (65.4)	148 (61.2)	82 (66.1)	157 (65.1)	153 (62.7)	77 (63.1)
Race, n (%)
White	194 (78.9)	195 (80.6)	99 (79.8)	190 (78.8)	195 (79.9)	100 (82.0)
Black	43 (17.5)	36 (14.9)	21 (16.9)	39 (16.2)	43 (17.6)	18 (14.8)
Other	9 (3.7)	11 (4.5)	4 (3.2)	12 (5.0)	6 (2.5)	4 (3.3)
Age (years), mean (range)	62.5 (50–84)	61.5 (49–90)	61.6 (50–83)	61.7 (50–88)	62.3 (50–89)	61.6 (50–87)
BMI (kg/m^2), mean (range)	33.2 (19.3–56.8)	33.2 (18.5–61.9)	32.7 (19.0–57.8)	32.1 (19.2–59.7)	33.0 (20.8–62.5)	33.0 (17.6–61.4)
Smoker, n (%)	33 (13.4)	34 (14.0)	22 (17.7)	35 (14.5)	41 (16.8)	11 (9.0)
LDA use at randomization, n (%)	57 (23.2)	59 (24.4)	28 (22.6)	67 (27.8)	43 (17.6)	28 (23.0)
ACR functional class, n (%)
I	60 (24.4)	57 (23.6)	31 (25.0)	47 (19.5)	36 (14.8)	29 (23.8)
II	132 (53.7)	125 (51.7)	68 (54.8)	148 (61.4)	136 (55.7)	63 (51.6)
III	54 (22.0)	60 (24.8)	25 (20.2)	46 (19.1)	72 (29.5)	30 (24.6)
IV	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)

ACR = American College of Rheumatology; BMI = body mass index; CEL = celecoxib; LDA = low-dose aspirin; NAP/ESO = naproxen/esomeprazole magnesium; PBO = placebo.

Figure 2. Change from baseline to week 12 in mSODA pain scores (LS mean) in patients treated with naproxen/esomeprazole magnesium, celecoxib, and placebo (mITT population with last observation carried forward). 95% CI on treatment difference for naproxen/esomeprazole magnesium minus celecoxib in Study 307: −0.4, 1.9; P = 0.1828; and for Study 309: −1.8, 0.6; P = 0.2979. (CEL = celecoxib; mITT = modified intent-to-treat; LS = least squares; mSODA = modified Severity of Dyspepsia Assessment; NAP/ESO = naproxen/esomeprazole magnesium; PBO = placebo.)

Table II. Mean change from baseline to week 6 and week 12 in mSODA pain scores in LDA users and non-users (mITT population).

	Study 307				Study 309
	NAP/ESO	CEL	PBO	NAP/ESO—CEL	NAP/ESO	CEL	PBO	NAP/ESO—CEL
LDA users
n	57	58	28		67	43	27
Week 6 change from baseline
Mean (SD)	−5.4 (9.9)	−3.3 (8.9)	−3.5 (9.0)		−3.4 (9.8)	−3.4 (9.4)	−3.4 (9.8)
Week 12 change from baseline
Mean (SD)	−5.6 (10.2)	−3.7 (9.2)	−3.5 (9.0)		−3.8 (9.7)	−3.7 (9.4)	−3.8 (10.0)
LS mean	−5.1	−3.9	−4.1	−1.2	−4.8	−2.8	−2.8	−2.0
95% CI				−3.7, 1.4				−4.5, 0.5
P				0.3548				0.1124
LDA non-users
n	188	179	95		171	198	93
Week 6 change from baseline
Mean (SD)	−2.5 (8.9)	−4.8 (8.9)	−3.8 (9.3)		−4.3 (9.9)	−2.9 (8.6)	−3.1 (9.8)
Week 12 change from baseline
Mean (SD)	−2.8 (9.0)	−5.1 (9.1)	−4.2 (9.5)		−4.7 (10.1)	−3.2 (8.9)	−3.5 (9.8)
LS mean	−3.4	−4.8	−3.6	1.4	−3.8	−3.5	−4.7	−0.2
95% CI				0.1, 2.7				−1.6, 1.2
P				0.0330				0.7453

CEL = celecoxib; LDA = low-dose aspirin; LS = least squares; mITT = modified intent-to-treat; mSODA = modified Severity of Dyspepsia Assessment; NAP/ESO = naproxen/esomeprazole magnesium; PBO = placebo; SD = standard deviation.

Figure 3. Proportion of heartburn-free days (LS mean %) from baseline to week 12 in patients treated with naproxen/esomeprazole magnesium, celecoxib, and placebo (mITT population). 95% CI on treatment difference for naproxen/esomeprazole magnesium minus celecoxib in Study 307: −2.1, 12.7; and for Study 309: 2.5, 13.4. (CEL = celecoxib; mITT = modified intent-to-treat; LS = least squares; NAP/ESO = naproxen/esomeprazole magnesium; PBO = placebo.)

Table III. Summary of predefined UGI AEs and discontinuations as a result of UGI AEs or any AE (safety population).

	Study 307			Study 309
	NAP/ESO (n = 247)	CEL (n = 243)	PBO (n = 124)	NAP/ESO (n = 243)	CEL (n = 245)	PBO (n = 122)
Patients with any UGI AE, n (%)	41 (16.6)	41 (16.9)	24 (19.4)	46 (18.9)	53 (21.6)	25 (20.5)
UGI AEs reported by ≥3% of patients,^a n (%)
Dyspepsia	13 (5.3)	19 (7.8)	14 (11.3)	28 (11.5)	33 (13.5)	16 (13.1)
Nausea	12 (4.9)	6 (2.5)	6 (4.8)	5 (2.1)	9 (3.7)	3 (2.5)
Upper abdominal pain	10 (4.0)	9 (3.7)	2 (1.6)	10 (4.1)	12 (4.9)	6 (4.9)
Vomiting	5 (2.0)	2 (0.8)	4 (3.2)	3 (1.2)	4 (1.6)	0 (0.0)
Discontinuations due to UGI AEs, n (%)	3 (1.2)	4 (1.6)	3 (2.4)	2 (0.8)	9 (3.7)	3 (2.5)
Discontinuations due to any AE, n (%)	18 (7.3)	16 (6.6)	7 (5.6)	16 (6.6)	22 (9.0)	5 (4.1)

^aAny treatment group of either study.

AE = adverse event; CEL = celecoxib; NAP/ESO = naproxen/esomeprazole magnesium; PBO = placebo; UGI = upper gastrointestinal.

Table IV. Treatment-emergent AEs: Overall and reported by ≥ 3% of patients in any treatment group of either study (safety population).

	Study 307			Study 309
	NAP/ESO (n = 247)	CEL (n = 243)	PBO (n = 124)	NAP/ESO (n = 243)	CEL (n = 245)	PBO (n = 122)
Patients with any AE, n (%)	129 (52.2)	110 (45.3)	65 (52.4)	132 (54.3)	132 (53.9)	61 (50.0)
AEs reported by ≥ 3% of patients in any treatment group of either study, n (%)
Diarrhea	15 (6.1)	8 (3.3)	3 (2.4)	12 (4.9)	6 (2.4)	6 (4.9)
Dyspepsia	13 (5.3)	19 (7.8)	14 (11.3)	28 (11.5)	33 (13.5)	16 (13.1)
Nausea	12 (4.9)	6 (2.5)	6 (4.8)	5 (2.1)	9 (3.7)	3 (2.5)
Upper abdominal pain	10 (4.0)	9 (3.7)	2 (1.6)	10 (4.1)	12 (4.9)	6 (4.9)
Constipation	9 (3.6)	5 (2.1)	2 (1.6)	8 (3.3)	5 (2.0)	1 (0.8)
Peripheral edema	9 (3.6)	3 (1.2)	1 (0.8)	6 (2.5)	3 (1.2)	2 (1.6)
Dizziness	7 (2.8)	2 (0.8)	4 (3.2)	8 (3.3)	2 (0.8)	1 (0.8)
Headache	7 (2.8)	10 (4.1)	5 (4.0)	6 (2.5)	8 (3.3)	8 (6.6)
Arthralgia	5 (2.0)	5 (2.1)	3 (2.4)	2 (0.8)	9 (3.7)	1 (0.8)
Sinusitis	5 (2.0)	3 (1.2)	4 (3.2)	0 (0.0)	3 (1.2)	2 (1.6)
Vomiting	5 (2.0)	2 (0.8)	4 (3.2)	3 (1.2)	4 (1.6)	0 (0.0)
Nasopharyngitis	3 (1.2)	3 (1.2)	5 (4.0)	4 (1.6)	4 (1.6)	0 (0.0)
Back pain	2 (0.8)	5 (2.1)	4 (3.2)	4 (1.6)	9 (3.7)	1 (0.8)
Cough	2 (0.8)	1 (0.4)	5 (4.0)	5 (2.1)	2 (0.8)	2 (1.6)

AE = adverse event; CEL = celecoxib; NAP/ESO = naproxen/esomeprazole magnesium; PBO = placebo.