Tolerability of NGX-4010, a capsaicin 8% patch, in conjunction with three topical anesthetic formulations for the treatment of neuropathic pain

Figures & data

Figure 1 Overview of patient randomization and disposition.

Table 1 Demographics and baseline characteristics

Patients	L.M.X.4 (n = 39)	Topicaine (n = 38)	Betacaine (n = 40)
Age (years), mean ± SD	63 ± 13	62 ± 12	58 ± 11
Male, %	56	61	58
Race, n (%)
White	28 (72)	28 (74)	34 (85)
Black or African American	5 (13)	3 (8)	2 (5)
Asian	1 (3)	0	0
Other	5 (13)	7 (18)	3 (8)
Neuropathic pain syndrome, n (%)
PDN	30 (77)	29 (76)	32 (80)
PHN	9 (23)	8 (21)	8 (20)
H IV-DSP	0	1 (3)	0
Duration of pain (years), mean ± SD	5.3 ± 5.55	4.5 ± 4.90	3.8 ± 3.91
Baseline pain level, mean ± SD (range)	5.6 ± 1.56 (2.5–8.2)	5.9 ± 1.44 (3.5–8.4)	5.4 ± 1.27 (3.0–7.8)
Baseline concomitant pain medication usea, n (%)	24 (62)	19 (50)	23 (58)

a Note: A patient was defined as being on concomitant pain medication if he/she was on an anticonvulsant, non-SSRI antidepressant, or opioid that was used on day −1 and was taken for a total duration of at least 7 consecutive days.

Abbreviations: HIV-DSP, human immunodeficiency virus-associated distal sensory polyneuropathy; PDN, painful diabetic neuropathy; PHN, post-herpetic neuralgia; SD, standard deviation; SSRI, non-selective serotonin reuptake inhibitor.

Table 2 Treatment-emergent adverse events that occurred in more than one patient in any of the anesthetic groups

System organ class preferred term	L.M.X.4 (n = 39)	Topicaine (n = 38)	Betacaine (n = 40)
Patients reporting one or more treatment-emergent AEs, n (%)	23 (59)	19 (50)	23 (58)
Cardiac disorders, n (%)	2 (5)	2 (5)	0
Cardiac failure congestive	2 (5)	0	0
Gastrointestinal disorders, n (%)	6 (15)	4 (11)	2 (5)
Nausea	2 (5)	4 (11)	0
Toothache	2 (5)	0	1 (3)
General disorders and administration-site conditions, n (%)	13 (33)	14 (37)	12 (30)
Application-site burning	7 (18)	8 (21)	3 (8)
Application-site dryness	2 (5)	0	2 (5)
Application-site edema	0	2 (5)	0
Application-site pain	3 (8)	5 (13)	3 (8)
Application-site pruritus	1 (3)	1 (3)	2 (5)
Application-site swelling	1 (3)	5 (13)	2 (5)
Infections and infestations, n (%)	15 (38)	7 (18)	8 (20)
Nasopharyngitis	0	4 (11)	1 (3)
Urinary tract infection	2 (5)	1 (3)	1 (3)
Musculoskeletal and connective tissue disorders, n (%)	10 (26)	4 (11)	6 (15)
Muscle spasm	2 (5)	0	0
Pain in extremity	1 (3)	2 (5)	1 (3)

Abbreviation: AE, adverse event.

Table 3 Change in “pain now” NPRS score from before topical anesthetic application on the day of treatment

	L.M.X.4 (n = 39)	Topicaine (n = 38)	Betacaine (n = 40)
25 min after patch application, mean ± SD	−2.2 ± 2.76	−0.9 ± 3.19	−1.9 ± 2.43
55 min after patch application, mean ± SD	−0.9 ± 3.72	0.6 ± 3.90	−0.3 ± 3.08
Within 5 min after patch removal, mean ± SD	−0.8 ± 3.29	0.1 ± 3.10	−0.1 ± 2.48
25 min after patch removal, mean ± SD	−0.6 ± 3.23	−0.4 ± 2.41	−1.0 ± 2.56
55 min after patch removal, mean ± SD	−0.5 ± 3.55	−0.7 ± 2.53	−1.1 ± 2.93
85 min after patch removal, mean ± SD	−0.3 ± 3.48c	−0.8 ± 2.68	−1.4 ± 2.96
155 min after patch removal, mean ± SD	−0.2 ± 3.59	−1.2 ± 2.49	−1.5 ± 2.80
Patients reporting a ≥33% pain increase from baseline during the first 48 hours, n (%)	28 (72)	28 (74)	30 (75)
P valuea	–	0.832	0.747
Patients using medication for treatment-related discomfort during days 0–5, n (%)	20 (51)	26 (68)	20 (50)
P valueb	–	0.195	0.922

a Notes: P value was computed from a Cochran–Mantel–Haenszel test, adjusted for treatment duration, comparing the proportions between the L.M.X.4 group and the other two topical anesthetic groups;

b P value was computed from a chi-squared test comparing the proportions between the L.M.X.4 group and the other two topical anesthetic groups;

c 38 patients only.

Abbreviation: SD, standard deviation.

Table 4 Maximum dermal assessment scores from removal of patch through termination

Score (0 to 7)a	L.M.X.4 (n = 39)	Topicaine (n = 38)	Betacaine (n = 40)
0, n (%)	10 (26)	10 (26)	14 (35)
1, n (%)	10 (26)	10 (26)	11 (28)
2, n (%)	15 (38)	17 (45)	13 (33)
3, n (%)	2 (5)	0	1 (3)
4, n (%)	1 (3)	1 (3)	1 (3)
5, n (%)	1 (3)	0	0
6, n (%)	0	0	0
7, n (%)	0	0	0
P valueb	–	0.916	0.284

a Notes: 0 = no evidence of irritation; 1 = minimal erythema, barely perceptible; 2 = definite erythema, readily visible; minimal edema or minimal papular response; 3 = erythema and papules; 4 = definite edema; 5 = erythema, edema, and papules; 6 = vesicular eruption; 7 = strong reaction spreading beyond test site.

b P value was computed from a Cochran–Mantel–Haenszel test comparing distribution of maximum score (0, 1, ≥2) between the L.M.X.4 group and the other two topical anesthetics groups.

Table 5 Efficacy of NGX-4010

	L.M.X.4	Topicaine	Betacaine
NPRS scores
Baseline, LS mean ± SE	5.6 ± 0.23	5.9 ± 0.23	5.4 ± 0.23
Weeks 2–12, n	39	38	40
Actual (LS mean ± SE)	3.9 ± 0.32	3.8 ± 0.33	4.0 ± 0.32
Change from baseline (LS mean ± SE)	−1.7 ± 0.32	−1.8 ± 0.33	−1.6 ± 0.32
Percentage change from baseline (LS mean ± SE)	−31.8 ± 5.61	−34.3 ± 5.72	−27.2 ± 5.56
P value^a	–	0.757	0.563
Patients with ≥30% decrease from baseline to weeks 2–12, n (%)	18 (46)	19 (50)	18 (45)
P valueb	–	0.588	0.864
Patients with ≥50% decrease from baseline to weeks 2–12, n (%)	13 (33)	14 (37)	11 (28)
P valueb	–	0.610	0.608
PGIC
Week 12, n	36	37	38
Much improved (very much, much), n (%)	14 (39)	13 (35)	16 (42)
Improved (very much, much, slightly), n (%)	21 (58)	24 (65)	27 (71)

Notes: P value was computed using ANCOVA to test for difference between the L.M.X.4 group and the other two topical anesthetic groups.

b P value was computed using logistic regression to test for difference between the L.M.X.4 group and the other two topical anesthetic groups.

Abbreviations: ANCOVA, analysis of covariance; LS mean, least squares mean; NPRS, Numeric Pain Rating Scale; PGIC, Patient Global Impression of Change; SE, standard error.