Efficacy and safety of low-dose SoluMatrix meloxicam in the treatment of osteoarthritis pain: a 12-week, phase 3 study

Figures & data

Figure 1. Patient disposition. ^aOne patient withdrew prior to administration of the study drug; hence, 402 patients were in the intent-to-treat and safety populations. ^bOne patient randomized to the SoluMatrix meloxicam 5 mg group received SoluMatrix meloxicam 10 mg and was recorded in the SoluMatrix meloxicam 10 mg group for analyses completed on the safety population, but remained in the 5 mg group for the analyses completed on the intent-to-treat population.

Table 1. Patient demographics and baseline characteristics.

	SoluMatrix meloxicam 5 mg	SoluMatrix meloxicam 10 mg	Placebo
Sex, n (%)	n = 138	n = 131	n = 133
Male	49 (35.5)	47 (35.9)	41 (30.8)
Female	89 (64.5)	84 (64.1)	92 (69.2)
Race, n (%)	n = 138	n = 131	n = 133
American Indian or Alaska Native	2 (1.4)	1 (0.8)	0
Asian	0	1 (0.8)	0
Black or African American	27 (19.6)	29 (22.1)	23 (17.3)
Native Hawaiian or Other Pacific Islander	2 (1.4)	2 (1.5)	0
White	108 (78.3)	98 (74.8)	110 (82.7)
Ethnicity, n (%)	n = 138	n = 131	n = 133
Hispanic or Latino	10 (7.2)	12 (9.2)	11 (8.3)
Not Hispanic or Latino	128 (92.8)	119 (90.8)	122 (91.7)
Age, years	n = 138	n = 131	n = 133
Mean (SD)	60.8 (9.05)	60.2 (8.77)	61.1 (9.26)
Median	60.0	60.0	60.0
Min–Max	42–83	40–84	42–87
Weight, kg	n = 138	n = 131	n = 133
Mean (SD)	89.0 (17.00)	85.9 (16.82)	89.2 (17.27)
Median	90.7	83.9	87.9
Min–Max	45.1–127.0	50.8–136.1	49.9–134.9
Height, cm	n = 138	n = 131	n = 133
Mean (SD)	168.9 (10.28)	167.9 (9.66)	168.6 (10.37)
Median	170.2	167.6	166.0
Min–Max	144.8–195.6	142.2–190.5	147.3–198.1
BMI, kg/m^2	n = 138	n = 131	n = 133
Mean (SD)	31.1 (4.77)	30.5 (5.31)	31.3 (4.95)
Median	31.1	30.2	30.9
Min–Max	18.1–40.7	18.7–39.9	18.8–43.8
Baseline WOMAC pain subscale score (0–100 mm scale)	n = 139	n = 130	n = 133
Mean (SD)	72.51 (15.36)	72.19 (13.94)	73.20 (15.47)
Min–Max	(44.2–99.0)	(40.4–100.0)	(41.6–100.0)
Baseline WOMAC function subscale score (0–100 mm scale)	n = 138	n = 130	n = 132
Mean (SD)	66.83 (18.05)	67.66 (16.87)	68.61 (17.62)
Min–Max	(24.6–98.1)	(7.3–96.6)	(22.1–98.9)
Baseline WOMAC stiffness subscale score (0–100 mm scale)	n = 139	n = 130	n = 132
Mean (SD)	70.30 (18.37)	69.19 (19.57)	72.65 (17.06)
Min–Max	(8.5–98.5)	(18.5–99.5)	(21.0–100.0)
Baseline total WOMAC score (0–100 mm scale)	n = 138	n = 130	n = 131
Mean (SD)	68.27 (16.32)	68.74 (15.19)	69.75 (16.13)
Min–Max	(31.8–97.0)	(16.0–96.7)	(27.0–98.6)
Target joint of OA, n (%)	n = 138	n = 131	n = 133
Hip	15 (10.9)	14 (10.7)	21 (15.8)
Knee	123 (89.1)	117 (89.3)	112 (84.2)

BMI, body mass index; OA, osteoarthritis; SD, standard deviation; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 2. Comparison of mean change from baseline in WOMAC pain subscale scores at weeks 2, 6, and 12 in patients with osteoarthritis. *P ≤ 0.024. †P = 0.1486. P values compared with placebo. All analyses are based on protocol-defined MMRM analysis (ITT population). ITT, intent-to-treat; LS, least squares; MMRM, mixed-model repeated measures; SE, standard error; WOMAC, Western Ontario and McMaster Universities Arthritis Index.

Table 2. Change in WOMAC pain subscale score from baseline comparison vs placebo at week 12 by MMRM and sensitivity analyses.

	SoluMatrix meloxicam 5 mg (n = 139)	SoluMatrix meloxicam 10 mg (n = 130)	Placebo (n = 133)
Protocol-defined MMRM (ITT Population)
Comparison vs placebo	n = 131	n = 119	n = 127
Difference in LS mean (SE)	−10.84 (3.10)	−8.74 (3.15)	–
95% CI for difference	(−16.93, −4.75)	(−14.94, −2.53)	–
P value	0.0005	0.0059	–
MMRM (PP Population)
Comparison vs placebo	n = 106	n = 98	n = 104
Difference in LS mean (SE)	−10.52 (3.30)	−10.53 (3.37)	–
95% CI for difference	(−17.02, −4.02)	(−17.16, −3.89)	–
P value	0.0016	0.0020	–
Penalized MMRM (ITT Population)
Comparison vs placebo	n = 129	n = 116	n = 119
Difference in LS mean (SE)	−9.43 (3.11)	−8.00 (3.18)	–
95% CI for difference	(−15.55, −3.31)	(−14.25, −1.75)	–
P value	0.0026	0.0122	–
Pattern-mixture Model (ITT Population)
Comparison vs placebo	n = 131	n = 119	n = 127
Difference in LS mean (SE)	−11.74 (3.09)	−8.82 (3.18)	–
95% CI for difference	(−17.79, −5.68)	(−15.05, −2.60)	–
P value	0.0001	0.0054	–
Silverman Integrated Rank Analysis (ITT Population)
Comparison vs placebo	n = 124	n = 113	n = 118
Difference in LS mean (SE)	−45.77 (10.92)	−45.35 (11.10)	–
95% CI for difference	(−67.25, −24.29)	(−67.20, −23.51)	–
P value	<0.0001	<0.0001	–

CI, confidence interval; ITT, intent to treat; LS, least squares; MMRM, mixed-model repeated measures; PP, per protocol; SE, standard error; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

P values compared with placebo.

Figure 3. Comparison of mean change from baseline in the WOMAC (A) function and (B) stiffness subscale scores at weeks 2, 6, and 12 in patients with osteoarthritis. *P ≤ 0.0014. †P = 0.1065. ‡P ≤ 0.0379. P values compared with placebo. All analyses are based on protocol-defined MMRM analysis (ITT population). ITT, intent-to-treat; LS, least squares; MMRM, mixed-model repeated measures; SE, standard error; WOMAC, Western Ontario and McMaster Universities Arthritis Index.

Figure 4. Continuous responder analysis of the WOMAC pain subscale scores at week 12 in patients with osteoarthritis.

Table 3. Summary of most frequent treatment-emergent AEs (≥1% of patients in any group).

Adverse event	SoluMatrix meloxicam 5 mg (n = 138)	SoluMatrix meloxicam 10 mg (n = 131)	SoluMatrix meloxicam groups combined (n = 269)	Placebo (n = 133)
Diarrhea	4 (2.9)	3 (2.3)	7 (2.6)	1 (0.8)
Headache	2 (1.4)	5 (3.8)	7 (2.6)	4 (3.0)
Nausea	3 (2.2)	3 (2.3)	6 (2.2)	0
Osteoarthritis	4 (2.9)	1 (0.8)	5 (1.9)	3 (2.3)
UTI	3 (2.2)	2 (1.5)	5 (1.9)	3 (2.3)
Constipation	2 (1.4)	2 (1.5)	4 (1.5)	2 (1.5)
URI	2 (1.4)	2 (1.5)	4 (1.5)	2 (1.5)
Abdominal discomfort	1 (0.7)	3 (2.3)	4 (1.5)	0
Nasopharyngitis	1 (0.7)	2 (1.5)	3 (1.1)	0
Dry mouth	2 (1.4)	0	2 (0.7)	0
Hypertension	0	2 (1.5)	2 (0.7)	1 (0.8)
Toothache	0	2 (1.5)	2 (0.7)	1 (0.8)
Edema peripheral	0	1 (0.8)	1 (0.4)	2 (1.5)
Pain in extremity	1 (0.7)	0	1 (0.4)	2 (1.5)
Epicondylitis	0	0	0	2 (1.5)

AE, adverse event; URI, upper respiratory tract infection; UTI, urinary tract infection.

Data presented as n (%).

Table 4. Proportion of patients with clinical laboratory assessments of potential concern.

Analyte	SoluMatrix meloxicam 5 mg (n = 138)	SoluMatrix meloxicam 10 mg (n = 131)	SoluMatrix meloxicam groups combined (n = 269)	Placebo (n = 133)
Alkaline phosphatase (>1.5 × ULN)	0	3 (2.3)	3 (1.1)	2 (1.5)
ALT (>3 × ULN)	1 (0.7)	2 (1.6)	3 (1.1)	0
AST (>3 × ULN)	0	2 (1.6)	2 (0.8)	0
Bilirubin (>2 × ULN)	0	1 (0.8)	1 (0.4)	0
BUN (≥24 mg/dL)	28 (20.4)	23 (17.8)	51 (19.2)	10 (7.6)
Creatinine (≥1.5 × ULN)	1 (0.7)	1 (0.8)	2 (0.8)	0
Glucose (≥200 mg/dL)	7 (5.2)	7 (5.4)	14 (5.3)	12 (9.1)
Glucose (≤55 mg/dL)	1 (0.7)	0	1 (0.4)	1 (0.8)
Potassium (≥5.5 mmol/L)	7 (5.2)	3 (2.3)	10 (3.8)	6 (4.5)

ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; ULN, upper limit of normal.

Data presented as n (%).