Pharmacokinetics and Adhesion of Lidocaine Topical System 1.8% With Water Exposure

Phase 1

Completed

Brief Summary: The objectives of this study are to evaluate the adhesion performance and pharmacokinetics of ZTlido (lidocaine topical system) 1.8% during swimming, showering, and under normal conditions.

Detailed Description: In this Phase 1, open-label, three-period crossover study, 24 healthy, adult male and female subjects are randomized to 1 of 3 treatment sequences. During each treatment period, subjects have one lidocaine topical system applied to their back for 12 hours with a 4-day washout between treatments. In each treatment period, the subject will either swim (Treatment A), shower (Treatment B), or refrain from these activities (Treatment C) while wearing the topical system. Blood samples for lidocaine PK will be collected pre-dose until 24 hours. Adhesion will be monitored throughout the wear time and skin irritation will be assessed the topical system is removed.

Recruitment & Eligibility

Inclusion Criteria

Key

Exclusion Criteria

Allergy or known hypersensitivity to lidocaine, amide-type local anesthetics or any component of the product formulation
Any major medical illness 3 months prior or any significant history or ongoing chronic medical illness affecting the major body systems, including the skin
Subjects with conditions that might affect application of the product or its adhesive properties (including psoriasis, eczema, atopic dermatitis, damaged or irritated epidermal layer, and excessive hair or oil on the skin)
Use of antiarrhymthic drugs (such as tocainide and mexiletine) and local anesthetics within 14 days prior to product application.
History of addiction, abuse, or misuse of any drug
Use of nicotine-containing products within 30 days

Arm && Interventions

Group	Intervention	Description
Lidocaine topical system with showering (Treatment B)	Lidocaine topical system 1.8%	One topical system is applied to the mid- to upper-back for 12 hours. Subjects take a 10-minute shower 8 hours after topical system application.
Lidocaine topical system under normal conditions (Treatment C)	Lidocaine topical system 1.8%	One topical system is applied to the mid- to upper-back for 12 hours. Topical systems are not exposed to water during this period.
Lidocaine topical system with swimming (Treatment A)	Lidocaine topical system 1.8%	One topical system is applied to the mid- to upper-back for 12 hours. Subjects swim for 15 minutes in a heated pool 4 hours after topical system application.

Primary Outcome Measures

Name	Time	Method
Mean cumulative adhesion score	Over 12 hours	Adhesion to skin assessed by FDA 0-4 scoring system. The scoring for adhesion of patches is indicated as follows: 0 = ≥ 90% Adhered (essentially no lift off the skin), 1 = ≥ 75% to \< 90% Adhered (some edges only lifting off the skin), 2 = ≥ 50% to \< 75% Adhered (less than half of the patch lifting off the skin), \> 0% to \< 50% Adhered but not detached (more than half of the patch lifting off the skin without falling off), and 4 = 0% adhered (patched completely detached). The cumulative adhesion score is calculated as the sum of scores at each assessment time point (3, 4.5, 7, 8.5, and 12 hours).

Secondary Outcome Measures

Name	Time	Method
Area under the plasma concentration-time curve (AUC) from Time 0 to Time 24 hours	0, 1.5, 3.0, 6.0, 9.0, 12.0, 15.0, 18.0, 24.0 hours post-dose	Area under the plasma concentration versus time curve from 0 to 24 hours of lidocaine in plasma
Area under the plasma concentration-time curve (AUC) from Time 0 to Time Infinity	0, 1.5, 3.0, 6.0, 9.0, 12.0, 15.0, 18.0, 24.0 hours post-dose	Area under the plasma concentration versus time curve from 0 to infinite time of lidocaine in plasma
Peak plasma concentration (Cmax) of lidocaine	0, 1.5, 3.0, 6.0, 9.0, 12.0, 15.0, 18.0, 24.0 hours post-dose	Peak plasma concentration of lidocaine after product application for 12 hours
Dermal Response Score	12.5 and 14 hours post-dose	Product tolerability is assessed by Dermal Response Score. The application site is evaluated 30 minutes and 2 hours after product removal (12.5 and 14 hours post-dose, respectively). Response score from 0 to 7; 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 (i.e., application) site.