Open-Label Adhesion Performance Studies of a New Lidocaine Topical System 1.8% versus Lidocaine Patches 5% and Lidocaine Medicated Plaster 5% in Healthy Subjects

Figures & data

Table 1 Characteristics of Studied Lidocaine Topical Products

	Lidocaine Topical System 1.8%	Lidocaine Patch 5%	Lidocaine Medicated Plaster 5%	Mylan Lidocaine Patch 5%
Formulation	Nonaqueous polymer	Hydrogel	Hydrogel	Nonaqueous polymer
Lidocaine content	36mg (18 mg per gram of adhesive: 1.8%)	700mg (50 mg per gram of adhesive: 5%)	700 mg (50 mg per gram of adhesive: 5%)	140 mg (50 mg per gram of adhesive: 5%)
Bioavailability	~ 45%	~3 ± 2%	~3 ± 2%	~11 ± 4%
Residual drug	~20 mg	≥ 665 mg	≥ 665 mg	~115 mg
Release liner	Perforated	Not perforated	Not perforated	Not perforated
Size	10 cm x 14 cm	10 cm x 14 cm	10 cm x 14 cm	10 cm x 14 cm
Thickness	0.08 cm	0.16 cm	0.16 cm	0.02 cm
Weight	2 g adhesive	14 g adhesive	14 g adhesive	2.8 g adhesive

Notes: ZTLIDO^® (lidocaine topical system) 1.8% Prescribing Information. 11/2018. LIDODERM^® (lidocaine patch 5%) Prescribing Information. 01/2015. VERSATIS^® (lidocaine medicated plaster 5%) Prescribing information. 07/2018. Mylan Lidocaine Patch 5% Prescribing information. 01/2015.

Table 2 Subject Demographics and Baseline Characteristics

Characteristics	Study 1 (n=54)	Study 2 (n=47)	Study 3 (n=24)
Age, years
Mean (SD)	30.1 (12.5)	43.1 (10.8)	34.79 (13.39)
Median	25.0	47.0	32.00
Range	18–58	19–59	19–64
Sex, n (%)
Male	16 (29.6%)	35 (74.5%)	9 (37.5%)
Female	38 (70.4%)	12 (25.5%)	15 (62.5%)
Race, n (%)
White	46 (85.2%)	22 (46.8%)	15 (62.5%)
Black	5 (9.3%)	21 (44.7%)	4 (16.7%)
Asian	2 (3.7%)	3 (6.4%)	3 (12.5%)
Other	1 (1.9%)	1 (2.1%)	0 (0%)

Abbreviation: SD, standard deviation.

Table 3 Mean Adhesion Scores Using FDA Scales for Lidocaine Topical System 1.8%, Lidocaine Patch 5%, and Lidocaine Medicated Plaster (Studies 1, 2, and 3)

	Study 1	Study 2			Study 3*
Parameters	Lidocaine Topical System 1.8% (n=54)	Lidocaine Topical System 1.8% (n=44)	Lidocaine Patch 5% (n=44)	Lidocaine Medicated Plaster 5% (n=44)	Lidocaine Topical System 1.8% (n=24)	Generic Lidocaine Patch 5% (n=24)
Mean cumulative adhesion score (FDA scale), mean ± SD	0.04 ± 0.138	0.20 ± 0.38	1.01 ± 0.66	0.89 ± 0.66	0.17 ± 0.48	2.63 ± 0.58
Minimum score*	0	0	0	0	0	0
Maximum score*	1	3	4	4	2	4

Note: *Percent adhesion data were converted to corresponding FDA adhesion rating scale scores for Study 3.

Figure 1 Adhesion assessments at the end of the dosing period (12 hours). The proportion of subjects with at least 90% adhesion (using the FDA adhesion rating scale) at the end of the 12-hour application period and the proportion of subjects who had experienced 0% adhesion (complete detachment) at any time point throughout the study in (A) Study 1 (n=54); (B) Study 2 (n=44); and (C) Study 3 (n=24).

Table 4 Mean Percent Adhesion Over Time for Lidocaine Topical System 1.8% and Lidocaine Patch/Plaster 5% Comparators (Studies 2 and 3)

	Study 2			Study 3
Mean Percent Adhesion Score	Lidocaine Topical System 1.8% (n=44)	Lidocaine Patch 5% (n=44)	Lidocaine Medicated Plaster 5% (n=44)	Lidocaine Topical System 1.8% (n=24)	Generic Lidocaine Patch 5% (n=24)
0 hours (mean ± SD)	100.0 ± 0.0	97.2 ± 2.9	97.2 ± 3.9	99.5 ± 0.7	77.6 ± 17.3
3 hours (mean ± SD)	96.9 ± 7.3	84.7 ± 13.1	86.0 ± 15.0	97.0 ± 4.8	51.9 ± 22.2
6 hours (mean ± SD)	95.0 ± 8.6	78.5 ± 18.0	80.9 ± 16.8	96.3 ± 5.5	40.8 ± 22.9
9 hours (mean ± SD)	91.8 ± 10.5	70.9 ± 22.2	75.7 ± 20.0	94.7 ± 7.1	31.2 ± 23.4
12 hours (mean ± SD)	88.7 ± 13.8	63.3 ± 24.2	68.4 ± 24.4	93.4 ± 7.2	26.8 ± 23.0
Mean cumulative adhesion % (mean ± SD)	93.1 ± 9.8	74.4 ± 18.3	77.8 ± 17.4	95.3 ± 5.9	37.7 ± 21.3

Figure 2 Mean percent adhesion over time. Mean percent adhesion scores were evaluated every 3 hours over the 12-hour application period. (A) In Study 2, there was a significant difference favoring the lidocaine topical system 1.8% over the lidocaine patch 5% and lidocaine medicated plaster 5% at baseline and at each time point after application (P<0.0001). (B) In Study 3, there was a significant difference favoring the lidocaine topical system 1.8% over the generic lidocaine patch 5% at baseline and at each time point after application (P<0.0001 for all comparisons).

Figure 3 Representative adhesion performance with the FDA score (denoted in red) in Studies 2 and 3. Subjects were treated with the lidocaine topical system 1.8% (top rows in panels A and B), lidocaine patch 5% (middle row in A), lidocaine medicated plaster 5% (bottom row in A), or generic lidocaine patch 5% (bottom row in B). Photographs were taken immediately following product application (0 hours) and at the end of the study after 12 hours (±15 minutes) of wear.

Figure 4 Mean irritation scores after product removal in Study 2. Irritation at the application site was assessed at 0.5 hours (+10 minutes), 2 hours (±15 minutes), and 12 hours (±30 minutes) after product removal. Irritation was graded using an 8-point scale of dermal response . Overall mean scores across all time points were not significantly different between the lidocaine topical system 1.8% and lidocaine patch 5% or lidocaine medicated plaster 5% (P=0.1656 for both comparisons). *Horizontal line represents a score of 2, defined as definite erythema, minimal edema, or minimal papular response and is considered clinically meaningful irritation.