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

A Phase 1, Open Label, Randomized, Three-treatment, Three-sequence, Three-period, Crossover Adhesion Performance and Pharmacokinetic Study of Lidocaine Topical System 1.8% in Healthy, Adult Subjects Under Normal and Two Water Stress Conditions

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Lidocaine topical system 1.8%

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Dilworth, Minnesota, United States, 56529
      • Axis Clinicals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Must be healthy based on medical history, laboratory work, and physical exam
• Body mass index ranging between 18.0-30.0 kg/m2, inclusive
• Capable of unaided swimming
• If childbearing potential, use of acceptable form of birth control
• In case of females of childbearing potential, have a negative serum pregnancy

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lidocaine topical system with swimming (Treatment A); 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.	Drug: Lidocaine topical system 1.8%; lidocaine patch; Other Names: ZTlido
Experimental: Lidocaine topical system with showering (Treatment B); 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.	Drug: Lidocaine topical system 1.8%; lidocaine patch; Other Names: ZTlido
Experimental: Lidocaine topical system under normal conditions (Treatment C); One topical system is applied to the mid- to upper-back for 12 hours. Topical systems are not exposed to water during this period.	Drug: Lidocaine topical system 1.8%; lidocaine patch; Other Names: ZTlido

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean cumulative adhesion score	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).	Over 12 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dermal Response Score	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.	12.5 and 14 hours post-dose
Peak plasma concentration (Cmax) of lidocaine	Peak plasma concentration of lidocaine after product application for 12 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-time curve (AUC) from Time 0 to Time 24 hours	Area under the plasma concentration versus time curve from 0 to 24 hours of lidocaine in plasma	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-time curve (AUC) from Time 0 to Time Infinity	Area under the plasma concentration versus time curve from 0 to infinite time of lidocaine in plasma	0, 1.5, 3.0, 6.0, 9.0, 12.0, 15.0, 18.0, 24.0 hours post-dose

Collaborators and Investigators

• Sponsor: Scilex Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Peter Boldingh, PharmD, Axis Clinicals

Publications and helpful links

General Publications

• Vought K, Greuber E, Patel K, Argoff C, Lissin D. A Randomized, Crossover, Adhesion Performance and Pharmacokinetic Study of a Lidocaine Topical System Under Conditions of Water Exposure in Healthy Subjects. J Pain Res. 2021 Aug 16;14:2459-2467. doi: 10.2147/JPR.S323789. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2019
• Primary Completion (Actual): August 31, 2019
• Study Completion (Actual): August 31, 2019

Study Registration Dates

• First Submitted: March 3, 2021
• First Submitted That Met QC Criteria: March 4, 2021
• First Posted (Actual): March 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 5, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix; Tissue Adhesions; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: SCI-LIDO-ADH-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No