Efficacy and Safety of the Lidoderm Patch Applied to Patients With Osteoarthritis of the Knee

Efficacy and Safety of the Lidocaine 5% Patch When Used as Adjunct Treatment in Patients With Osteoarthritis of the Knee Receiving Sub-Optimal Pain Relief From Their Current Analgesic Regimen

Patients with knee pain due to Osteoarthritis (OA) experiencing sub-optimal pain relief from their current analgesic regimen will participate in a pilot clinical trial to evaluate the effectiveness and tolerability of the Lidoderm Patch compared with placebo in treating knee pain from OA.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis of the Knee
• Intervention / Treatment: Drug: Lidoderm (Lidocaine 5% Patch); Drug: Placebo Patch

• Study Type: Interventional
• Enrollment (Actual): 169
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Paradise Valley, Arizona, United States, 85253
      • Arizona Arthritis Research, PLC
    • Phoenix, Arizona, United States, 85016
      • NextCare Institute For Clinical Research
    • Phoenix, Arizona, United States, 85050
      • HOPE Research Institute, LLC
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Clinical Research Consulting
    • Trumbull, Connecticut, United States, 06611
      • New England Research Associates, LLC
  • Florida
    • Clearwater, Florida, United States, 33761
      • Tampa Bay Medical Research, Inc.
    • Delray Beach, Florida, United States, 33484
      • Delray Research Associates
    • Saint Petersburg, Florida, United States, 33702
      • CNS Clinical Trials
    • Tampa, Florida, United States, 33606
      • Clinical Research of West Florida
  • Maryland
    • Frederick, Maryland, United States, 21702
      • Arthritis & Osteoporosis Center of Maryland
  • Missouri
    • Saint Peters, Missouri, United States, 63376
      • Midwest Pharmaceutical Research
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Arthritis Center of Nebraska
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • University Hospitals of Case Medical Center - Arthritis Translational Research Program
    • Cincinnati, Ohio, United States, 45245
      • Community Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Texas
    • San Antonio, Texas, United States, 78217
      • Radiant Research
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Advanced Pain Management & Rehabilitation, Hilltop Medical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 37 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion criteria:

• Male or female patients ≥37 years with moderate-to-severe OA related pain in one knee
• Body mass index (BMI) ≤40 kg/m2
• Symptomatic OA of the index knee diagnosed with a functional capacity of II or III according to ACR criteria classification Note: Patients with symptomatic contralateral knee OA with persistent pain ≤2 cm on a 0-10 cm PI-NRS for ≥2 months will be allowed to participate.
• Unchanged dose of analgesic medication for OA for at least 4 weeks prior to screening and for the duration of the study
• Able and willing to complete all paper and e-diary assessments required by protocol

Key Exclusion criteria:

• Pain in any joint other than the index joint that could interfere with the patient's assessment of pain in the index joint
• Compromised integrity of the intact, superficial skin layer
• A grade 1 or 4 Kellgren and Lawrence score on radiographic examination
• Recent injury to either knee causing pain and interference with daily activities (eg. walking)
• Recent surgery/procedure to either knee causing pain that could interfere with study assessments of pain, function, and QoL
• Known hypersensitivity or allergy to lidocaine, local anesthetics of the amide type, or any component of the product

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lidoderm (Lidocaine 5% Patch); Lidoderm (lidocaine 5% patch) 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h)	Drug: Lidoderm (Lidocaine 5% Patch); Topical Patch; Other Names: Lidoderm
Placebo Comparator: Placebo Patch; Placebo Patch 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h)	Drug: Placebo Patch; Topical Patch; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-Exit From Current Study Treatment	Time-to-exit was defined as the number of days at which a patient either met the switching criterion [a 2-category change in the Pain Relief Scale (PRS) score in the worsening direction (increasing pain or decreasing pain relief) for 2 consecutive days] or discontinued from the study. The PRS is a 9-point categorical rating scale to assess pain relief in the last 24 hours in which 0 = completely worse and 8 = complete pain relief. Traditional survival models that consider event times (e.g. median survival time) as independent and homogeneous across patients were not suitable for this study.	Baseline, Period 1 (up to 4 weeks ±2 days), Period 2 (up to 4 weeks ±2 days), Period 3 (up to 4 weeks ±2 days), or Premature Discontinuation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-Exit Due to Lack of Efficacy	Time-to-exit due to lack of efficacy was defined as a patient that met the switching criterion (a 2-category change in Pain Relief Scale (PRS) in the worsening direction [increasing pain or decreasing pain relief] for 2 consecutive days) or was discontinued from the current period or study due to lack of efficacy. The PRS is a 9-point categorical rating scale to assess pain relief in the last 24 hours in which 0 = completely worse and 8 = complete pain relief. No patients discontinued from the study due to lack of efficacy.	Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks), or Premature Discontinuation
Exit Status From Current Study Treatment - Yes	Exit status from a current study treatment was categorized as yes or no for patients who exited prior to the 4-week planned duration. This analysis supports the results of the primary analysis. The number of patients exiting (yes) is reported.	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks), or Premature Discontinuation
Overall Treatment Difference in the LSMeans of the Average of the Last Two Daily Pain Intensity Numerical Rating Scale (PI-NRS)	The Numerical Rating Scale (NRS) is an 11-point categorical rating scale to assess pain intensity (PI-NRS); 0= no pain and 10= worst possible pain. The scale is anchored on the left with "No Pain" and on the right with "Worst Possible Pain." Patients were to complete this assessment at approximately the same time each day during the double-blind treatment period in their e-diary. The overall treatment difference for the Lidoderm (lidocaine patch 5%) and placebo patch was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence.	Baseline, End of Period 1 (up to 4 weeks), End of Period 2 (up to 4 weeks) and End of Period 3 (up to 4 weeks)
Overall Treatment Difference in the LSMeans of the Average of the Last Two Daily Pain Relief Scale (PRS) Scores	The Pain Relief Scale (PRS) is a 9-point categorical rating scale to assess pain relief during the 24-hours since the last assessment; 0= completely worse and 8= complete pain relief. Patients completed this assessment each day during the run-in period and each day during the double-blind treatment phase in their e-diary.	Baseline, End of Period 1 (up to 4 weeks), End of Period 2 (up to 4 weeks) and End of Period 3 (up to 4 weeks)
Overall Treatment Difference of the LSMeans of the Pain Quality Assessment Scale (PQAS) Scores	The PQAS measures individual pain qualities and the impact of treatment on those qualities. Items 1-19 are each rated on an 11-point scale ranging from 0 (lowest score - no pain of that type) to 10 (highest score - the highest level of that type of pain). Average surface pain = average of PQAS items: cold, sensitive, itchy, numb, and tingling. Average deep pain = average of PQAS items: dull, cramping, throbbing, aching, and heavy. Average paroxymal pain = average of PQAS items: sharp, shooting, electric, and radiating.	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)
Patient Global Impression of Change From Baseline in Osteoarthritis (OA) Pain	Patients rated their overall impression of change from Baseline to the end of each period during the double-blind treatment period, including premature discontinuation. Change was rated using a categorical scale indicating: "very much worse" (0); "much worse" (1); "minimally worse" (2); "no change" (3); "minimally improved" (4); "much improved" (5); and "very much improved" (6).	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)
Investigator Global Impression of Change From Baseline in Osteoarthritis (OA) Pain	Investigators rated their overall impression of change from Baseline to the end of each period during the double-blind treatment period, including premature discontinuation. Change was rated using a categorical scale ranging from "very much worse" to "very much improved." A similar questionnaire was completed by the Investigator.	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)
Patient Global Assessment of Treatment Satisfaction	At the end of each period, patients rated their overall satisfaction with study treatment using a 5-point categorical scale indicating: 0 - very dissatisfied; 1 - dissatisfied; 2 - no preference; 3 - satisfied; and 4 - very satisfied.	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)
Investigator Global Assessment of Treatment Satisfaction	At the end of each period, investigators rated their overall satisfaction with study treatment using a 5-point categorical scale ranging from 0 (very dissatisfied) to 4 (very satisfied).	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Treatment Difference in LSMeans of Beck Depression Inventory Second Edition (BDI-II) Total Score	The BDI-II is a 21-item self-report instrument intended to assess the existence and severity of symptoms of depression. Patients were to consider each item as it related to the way they felt for the previous 2 weeks. Each of the 21 items corresponding to a symptom of depression was summed to give a single score for the BDI-II, with a 4-point scale for each item ranging from 0-3. A total score of 0-13 is minimal, 14-19 is mild, 20-28 is moderate, and 29-63 is severe. Values were based on measurements taken at Screening, at Baseline (Visit 3), and at the end of each period.	Baseline and end of treatment period (up to 4 weeks)
Quality of Life: Four Category Beck Depression Inventory Second Edition (BDI-II) Composite Score	The BDI-II is a 21-item self-report instrument intended to assess the existence and severity of symptoms of depression. Patients were to consider each item as it related to the way they felt for the previous 2 weeks. Each of the 21 items corresponding to a symptom of depression was summed to give a single score for the BDI-II, with a 4-point scale for each item ranging from 0-3. A total score of 0-13 is minimal, 14-19 is mild, 20-28 is moderate, and 29-63 is severe. Values were based on measurements taken at Screening, at Baseline (Visit 3), and at the end of each period.	Screening, Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)
Overall Treatment Difference in LSMeans for Continuous EuroQol Quality of Life Instrument (EQ-5D) Index Scores	Health status was assessed using the EuroQol Quality of Life Instrument (EQ-5D). Patients completed the EQ-5D assessment at Baseline (Day 0) and at each clinic visit (at least every 4 weeks) or at premature discontinuation. Values of the EQ-5D index score range from -1 (worst) to 1 (best).	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks), or Premature Discontinuation
Overall Treatment Difference in LSMeans for Continuous EuroQol Quality of Life Instrument (EQ-5D) Health Status Today Using a Visual Analog Scale (VAS)	Health status was assessed using the EuroQol Quality of Life Instrument (EQ-5D). Patients completed the EQ-5D assessment at Baseline and at the end of each period or at premature discontinuation. Values of the continuous EQ-5D health state today (VAS) ranged from 0 (worst imaginable health state) to 100 (best imaginable health state).	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks), or Premature Discontinuation
Quality of Life: Three-Category EuroQol Quality of Life Instrument (EQ-5D) General Health Today Compared to Last 12 Months	Health status was assessed using the EuroQol Quality of Life Instrument (EQ-5D). Patients completed the EQ-5D assessment at Baseline and at the end of each period or at premature discontinuation. Categories included Better, Much the Same, and Worse.	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks), or Premature Discontinuation
Overall Treatment Difference in LSMeans for Verran Snyder-Halpern (VSH) Sleep Scale	The VSH Sleep Scale is contained in a 15 item self-report instrument that measures the quality of a patient's sleep over the last 24 hours. Each item is scored on a 0-100 visual analog scale. The VSH is categorized into 3 sleep scales: disturbance (which measures delays and interruptions in sleep)[maximum score = 700], effectiveness (which measures how well sleep refreshed the individual) [maximum score = 600], and supplementation (which measures the need for napping) [maximum score = 400]. The higher the score the greater the value of the sleep characteristic for that patient.	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: Ernest A. Kopecky, PhD, MBA, Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: December 26, 2007
• First Submitted That Met QC Criteria: January 9, 2008
• First Posted (Estimate): January 10, 2008

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: September 7, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Osteoarthritis; Knee; Lidocaine; Lidoderm; Topical patch; Adjunct therapy
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; 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: EN3260-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No