Why carry out this study?
|
Chronic low back pain is one of the most common chronic pain disorders and often comprises mixed pain types. |
We hypothesized that combining a systemic transdermal patch containing the non-steroidal anti-inflammatory drug (NSAID) diclofenac sodium (DF systemic patch), which is effective for nociceptive pain, with an α2δ Ca2+ channel ligand, which is effective for neuropathic pain, would have additive effects in patients with chronic low back pain. |
What was learned from the study?
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In patients with chronic low back pain, the combination of the DF systemic patch and α2δ Ca2+ channel ligand appears to have additive effects, as shown by improvement in pain visual analog scale scores in the 150-mg combination group than in the α2δ Ca2+ channel ligand monotherapy (placebo group) placebo patch group. |
The population evaluated in this report did not experience gastrointestinal adverse events, which are typical adverse effects of NSAIDs, or lightheadedness or dizziness, which are commonly observed with α2δ Ca2+ channel ligands. |
Introduction
Methods
Patients
Statistical analyses
Results
Patient Disposition and Baseline Characteristics
Characteristic | Subpopulation (concomitant treatment with alpha-2-delta calcium channel ligand) | Overall study population (FAS) | ||||
---|---|---|---|---|---|---|
75-mg combination (N = 14) | 150-mg combination (N = 11) | Placebo (N = 22) | 75 mg (N = 136) | 150 mg (N = 135) | Placebo (N = 267) | |
Sex, n (%) | ||||||
Male | 6 (42.9) | 5 (45.5) | 12 (54.5) | 55 (40.4) | 56 (41.5) | 125 (46.8) |
Female | 8 (57.1) | 6 (54.5) | 10 (45.5) | 81 (59.6) | 79 (58.5) | 142 (53.2) |
Age, years | ||||||
Mean ± SD | 66.2 ± 9.3 | 66.4 ± 17.1 | 72.3 ± 9.3 | 64.1 ± 14.0 | 63.0 ± 15.0 | 63.8 ± 13.5 |
Minimum | 51 | 37 | 47 | 27 | 27 | 20 |
Maximum | 82 | 81 | 84 | 89 | 85 | 87 |
Body weight, kg | ||||||
Mean ± SD | 67.21 ± 13.25 | 66.62 ± 13.65 | 67.16 ± 12.59 | 62.88 ± 13.15 | 63.28 ± 13.57 | 63.59 ± 12.43 |
Minimum | 47.4 | 50.4 | 44.0 | 32.7 | 38.3 | 37.3 |
Maximum | 96.2 | 92.3 | 90.5 | 98.9 | 110.3 | 111.0 |
Mean 3-day VAS pain score at baseline, mm | ||||||
Mean ± SD | 66.69 ± 13.26 | 59.15 ± 12.10 | 60.80 ± 15.23 | 61.87 ± 12.92 | 61.48 ± 12.45 | 61.32 ± 13.13 |
Minimum | 40.3 | 41.3 | 40.3 | 40.3 | 40.3 | 40.3 |
Maximum | 81.3 | 84.3 | 90.0 | 96.0 | 93.0 | 99.0 |
Duration of disease, years | ||||||
Mean ± SD | 4.52 ± 5.25 | 5.04 ± 6.39 | 8.19 ± 10.00 | 5.31 ± 5.42 | 6.19 ± 5.87 | 5.82 ± 7.34 |
Minimum | 0.4 | 0.7 | 0.5 | 0.2 | 0.3 | 0.3 |
Maximum | 20.0 | 19.0 | 41.0 | 30.0 | 30.0 | 49.0 |
No. | Group | Underlying disorder of low back pain | Duration of treatment, days | Pain VAS score, mm | Alpha-2-delta calcium channel ligand | ||||
---|---|---|---|---|---|---|---|---|---|
Baselinea | After 2 weeks of treatmentb | Change | Concomitant drug | Daily dose, mg | Purpose of use | ||||
1 | 150 mg | Back pain | 14 | 84.3 | 75.3 | − 9.0 | Oral pregabalin | 100 | Low back pain |
2 | 150 mg | Lumbar spinal stenosis | 16 | 52.7 | 14.3 | − 38.3 | Oral pregabalin | 50 | Low back pain Right femoral greater trochanteric pain Right hip arthropathy |
3 | 150 mg | Lumbar spinal stenosis, spondylolisthesis | 14 | 49.7 | 27.3 | − 22.3 | Oral pregabalin | 25 | Low back pain |
4 | 150 mg | Spinal osteoarthritis | 14 | 59.3 | 10.0 | − 49.3 | Oral pregabalin | 100 | Low back pain |
5 | 150 mg | Spondylolisthesis | 14 | 59.0 | 51.7 | − 7.3 | Oral pregabalin | 50 | Numbness associated with underlying disorder causing low back pain |
6 | 150 mg | Intervertebral disc protrusion, intervertebral disc disorder | 14 | 69.7 | 69.0 | − 0.7 | Oral pregabalin | 150 | Low back pain |
7 | 150 mg | Back pain | 14 | 59.7 | 45.7 | − 14.0 | Oral pregabalin | 75 | Low back pain |
8 | 150 mg | Lumbar spinal stenosis, intervertebral disc protrusion | 14 | 41.3 | 28.0 | − 13.3 | Oral pregabalin | 150 | Low back pain Right lower extremity radicular sciatica |
9 | 150 mg | Spinal osteoarthritis | 14 | 64.0 | 43.7 | − 20.3 | Oral pregabalin | 150 | Sciatica |
10 | 150 mg | Intervertebral disc protrusion | 14 | 66.0 | 40.3 | − 25.7 | Oral pregabalin | 100 | Low back pain |
11 | 150 mg | Lumbar spinal stenosis | 14 | 45.0 | 20.0 | − 25.0 | Oral pregabalin | 150 | Peripheral neuropathy |
12 | 75 mg | Spinal osteoarthritis | 14 | 74.0 | 62.7 | − 11.3 | Oral mirogabalin | 30 | Low back pain |
13 | 75 mg | Intervertebral disc disorder | 14 | 74.7 | 78.0 | 3.3 | Oral pregabalin | 50 | Low back pain |
14 | 75 mg | Intervertebral disc protrusion | 16 | 74.0 | 65.0 | − 9.0 | Oral pregabalin | 100 | Low back pain |
15 | 75 mg | Intervertebral disc protrusion | 12 | 73.3 | 57.0 | − 16.3 | Oral pregabalin | 100 | Low back pain |
16 | 75 mg | Myofascial pain syndrome | 12 | 51.3 | 26.0 | − 25.3 | Oral pregabalin | 50 | Cervical disc herniation |
17 | 75 mg | Lumbar spinal stenosis, intervertebral disc protrusion, intervertebral disc disorder | 11c | 70.3 | NA | − 7.3 | Oral pregabalin | 50 | Low back pain |
18 | 75 mg | Lumbar spinal stenosis | 14 | 61.7 | 51.3 | − 10.3 | Oral pregabalin | 100 | Low back pain |
19 | 75 mg | Lumbar spinal stenosis, Spondylolisthesis | 14 | 43.7 | 35.0 | − 8.7 | Oral pregabalin | 75 | Low back pain |
20 | 75 mg | Intervertebral disc protrusion | 14 | 61.3 | 38.7 | − 22.7 | Oral pregabalin | 525 | Left sciatica |
21 | 75 mg | Spinal osteoarthritis | 12 | 40.3 | 37.3 | − 3.0 | Oral pregabalin | 75 | Neuropathic pain |
22 | 75 mg | Spinal osteoarthritis | 14 | 77.7 | 9.3 | − 68.3 | Oral pregabalin | 75 | Peripheral neuropathy |
23 | 75 mg | Lumbar spinal stenosis, spinal osteoarthritis, intervertebral disc protrusion | 14 | 69.0 | 56.3 | − 12.7 | Oral pregabalin | 75 | Neuropathic pain |
24 | 75 mg | Lumbar spinal stenosis, intervertebral disc protrusion | 14 | 81.3 | 44.0 | − 37.3 | Oral pregabalin | 75 | Low back pain |
25 | 75 mg | Lumbar spinal stenosis, intervertebral disc protrusion | 14 | 81.0 | 71.7 | − 9.3 | Oral pregabalin | 150 | Low back pain |
26 | Placebo | Spinal osteoarthritis | 14 | 79.0 | 60.3 | − 18.7 | Oral mirogabalin | 30 | Low back pain Peripheral neuropathic pain |
27 | Placebo | Lumbar spinal stenosis, spinal osteoarthritis, spondylolisthesis | 15 | 61.7 | 57.3 | − 4.3 | Oral mirogabalin | 5 | Low back pain |
28 | Placebo | Lumbar spinal stenosis | 15 | 47.7 | 45.7 | − 2.0 | Oral mirogabalin | 10 | Low back pain |
29 | Placebo | Spinal osteoarthritis | 16 | 90.0 | 50.0 | − 40.0 | Oral pregabalin | 50 | Low back pain |
30 | Placebo | Lumbar spinal stenosis | 14 | 52.3 | 50.0 | − 2.3 | Oral pregabalin | 100 | Neuropathic pain |
31 | Placebo | Lumbar spinal stenosis, spinal osteoarthritis | 14 | 54.3 | 31.7 | − 22.7 | Oral pregabalin | 50 | Neuropathic pain |
32 | Placebo | Spinal osteoarthritis | 14 | 76.7 | 58.0 | − 18.7 | Oral pregabalin | 50 | Low back pain |
33 | Placebo | Lumbar spinal stenosis | 2 c | 57.0 | NA | 12.0 | Oral pregabalin | 100 | Low back pain |
34 | Placebo | Lumbar spinal stenosis, intervertebral disc protrusion | 15 | 41.0 | 47.3 | 6.3 | Oral pregabalin | 150 | Peripheral neuropathy |
35 | Placebo | Lumbar spinal stenosis | 14 | 84.3 | 86.7 | 2.3 | Oral pregabalin | 150 | Low back pain |
36 | Placebo | Lumbar spinal stenosis, spinal osteoarthritis, spondylolisthesis, spinal instability | 14 | 40.7 | 45.0 | 4.3 | Oral pregabalin | 150 | Neuropathic pain |
37 | Placebo | Lumbar spinal stenosis | 7 c | 79.7 | NA | 7.0 | Oral pregabalin | 300 | Neuropathic pain |
38 | Placebo | Intervertebral disc protrusion | 14 | 60.7 | 48.3 | − 12.3 | Oral pregabalin | 150 | Neuropathic pain |
39 | Placebo | Lumbar spinal stenosis, intervertebral disc protrusion, intervertebral disc disorder | 15 | 56.3 | 57.0 | 0.7 | Oral pregabalin | 375 | Peripheral neuropathy |
40 | Placebo | Lumbar spinal stenosis, spinal osteoarthritis | 14 | 65.7 | 67.7 | 2.0 | Oral pregabalin | 150 | Peripheral neuropathic pain |
41 | Placebo | Spinal osteoarthritis, intervertebral disc disorder | 14 | 49.7 | 50.7 | 1.0 | Oral pregabalin | 75 | Low back pain Bilateral knee osteoarthritis |
42 | Placebo | Spinal osteoarthritis | 14 | 59.7 | 17.0 | − 42.7 | Oral pregabalin | 50 | Peripheral neuropathy |
43 | Placebo | Lumbar spinal stenosis | 14 | 71.7 | 68.3 | − 3.3 | Oral pregabalin | 50 | Low back pain |
44 | Placebo | Lumbar spinal stenosis | 14 | 40.3 | 39.0 | − 1.3 | Oral pregabalin | 50 | Low back pain |
45 | Placebo | Lumbar spinal stenosis | 15 | 50.0 | 53.7 | 3.7 | Oral pregabalin | 150 | Low back pain |
46 | Placebo | Osteoporosis, scoliosis | 14 | 77.0 | 75.0 | − 2.0 | Oral pregabalin | 150 | Lumbar spinal stenosis |
47 | Placebo | Lumbar spinal stenosis, spinal osteoarthritis | 14 | 42.3 | 45.7 | 3.3 | Oral pregabalin | 150 | Peripheral neuropathy |
Efficacy
Population | Group | Number of cases | Change in mean 3-day pain VAS score from baseline to week 2, LS mean, mm | Between-group difference in change from baseline in 3-day mean (95% CI) pain VAS score (vs. placebo), mm | P value (vs. placebo) |
---|---|---|---|---|---|
Overall study population (FAS) | 75 mg | 136 | − 18.52 | − 5.68, (− 9.34, − 2.01) | 0.0024a |
150 mg | 135 | − 18.52 | − 5.67, (− 9.34, − 2.00) | 0.0025a | |
Placebo | 267 | − 12.85 | |||
Subpopulation (participants with concomitant alpha-2-delta calcium channel ligand) | 75 mg combination | 14 | − 15.91 | − 9.77, (− 20.45, 0.92) | NA |
150 mg combination | 11 | − 21.23 | − 15.09, (− 26.45, − 3.73) | NA | |
Placebo | 22 | − 6.14 |
Safety
Adverse events | Adverse drug reactions (adverse events for which a causal relationship cannot be ruled out) | |||||
---|---|---|---|---|---|---|
75-mg combination (N = 14) | 150-mg combination (N = 11) | Placebo (N = 22) | 75-mg combination (N = 14) | 150-mg combination (N = 11) | Placebo (N = 22) | |
n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | |
Any AE | 5 (35.7) | 2 (18.2) | 4 (18.2) | 3 (21.4) | 1 (9.1) | 2 (9.1) |
AEs (MedDRA SOC, PT)a | ||||||
Cardiac disorders | 1 (7.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Tachycardia | 1 (7.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
General disorders and administration site conditions | 1 (7.1) | 0 (0.0) | 1 (4.5) | 1 (7.1) | 0 (0.0) | 1 (4.5) |
Application site erythema | 1 (7.1) | 0 (0.0) | 0 (0.0) | 1 (7.1) | 0 (0.0) | 0 (0.0) |
Application site pruritus | 0 (0.0) | 0 (0.0) | 1 (4.5) | 0 (0.0) | 0 (0.0) | 1 (4.5) |
Hepatobiliary disorders | 1 (7.1) | 1 (9.1) | 0 (0.0) | 1 (7.1) | 1 (9.1) | 0 (0.0) |
Hepatic function abnormal | 0 (0.0) | 1 (9.1) | 0 (0.0) | 0 (0.0) | 1 (9.1) | 0 (0.0) |
Hepatic steatosis | 1 (7.1) | 0 (0.0) | 0 (0.0) | 1 (7.1) | 0 (0.0) | 0 (0.0) |
Investigations | 4 (28.6) | 2 (18.2) | 2 (9.1) | 2 (14.3) | 1 (9.1) | 0 (0.0) |
Alanine aminotransferase increased | 0 (0.0) | 1 (9.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Blood creatine phosphokinase increased | 0 (0.0) | 1 (9.1) | 0 (0.0) | 0 (0.0) | 1 (9.1) | 0 (0.0) |
Blood bilirubin increased | 1 (7.1) | 0 (0.0) | 0 (0.0) | 1 (7.1) | 0 (0.0) | 0 (0.0) |
Blood pressure increased | 1 (7.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Neutrophil percentage decreased | 1 (7.1) | 0 (0.0) | 0 (0.0) | 1 (7.1) | 0 (0.0) | 0 (0.0) |
Neutrophil percentage increased | 1 (7.1) | 0 (0.0) | 0 (0.0) | 1 (7.1) | 0 (0.0) | 0 (0.0) |
Monocyte percentage increased | 1 (7.1) | 0 (0.0) | 2 (9.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Respiratory, thoracic and mediastinal disorders | 0 (0.0) | 0 (0.0) | 1 (4.5) | 0 (0.0) | 0 (0.0) | 1 (4.5) |
Interstitial lung disease | 0 (0.0) | 0 (0.0) | 1 (4.5) | 0 (0.0) | 0 (0.0) | 1 (4.5) |