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

• Sponsor: Endo Pharmaceuticals
• Information provided by (Responsible Party): Endo Pharmaceuticals

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition	Osteoarthritis of the Knee
Interventions	Drug: Lidoderm (Lidocaine 5% Patch); Drug: Placebo Patch
Enrollment	169

Participant Flow

Recruitment Details	This exploratory, Phase IIb study was initiated on March 6, 2007 at 21 study centers in the United States and completed on June 24, 2008.
Pre-assignment Details	During the active Run-in Period, eligible patients applied Lidoderm patches every 24 hours for 28 days. During the 12-week Double-blind Treatment Period, patients were randomized to apply Lidoderm patches or matching placebo patches every 24 hours for 4 weeks and then crossed over to the other treatment for the next two 4-week treatment periods.

Arm/Group Title	Run-in Period: Lidoderm	Treatment Sequence: Lidoderm - Placebo - Placebo	Treatment Sequence: Placebo - Lidoderm - Lidoderm
Arm/Group Description	Run-in Period with patients applying Lidoderm (lidocaine 5% patch) 10cm x 14cm each on the front and back of the index knee every 24 hours for up to 28 days (4 weeks).	Lidoderm (lidocaine 5% patch) 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for up to 4 weeks followed by matching placebo 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks	Matching placebo 10cm X 14cm patches each on the front and back of the index knee q24h for up to 4 weeks followed by Lidoderm (lidocaine 5% patch) 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks
Period Title: Run-In Period
Started	169	0	0
Completed	93	0	0
Not Completed	76	0	0
Reason Not Completed
Adverse Event	5	0	0
Protocol Violation	3	0	0
Did not qualify for randomization	54	0	0
Withdrawal by Subject	10	0	0
Informed Consent Withdrawn	4	0	0
Period Title: Double-Blind Treatment Period 1
Started	0 [1]	50 [2]	43 [2]
Completed	0	48	41
Not Completed	0	2	2
Reason Not Completed
Adverse Event	0	1	0
Protocol Violation	0	1	1
Withdrawal by Subject	0	0	1
[1] Participants completing the Run-in Period were then randomized to two different treatment sequences.; [2] N=21 randomized on or after 22JAN2008; included in mod. intent-to-treat (MITT) analysis population.
Period Title: Double-Blind Treatment Period 2
Started	0	48 [1]	41 [2]
Completed	0	47	39
Not Completed	0	1	2
Reason Not Completed
Adverse Event	0	1	0
Withdrawal by Subject	0	0	1
Other	0	0	1
[1] N=19 randomized on or after 22JAN2008; included in mod. intent-to-treat (MITT) analysis population.; [2] N=20 randomized on or after 22JAN2008; included in mod. intent-to-treat (MITT) analysis population.
Period Title: Double-Blind Treatment Period 3
Started	0	47 [1]	39 [1]
Completed	0	46	38
Not Completed	0	1	1
Reason Not Completed
Protocol Violation	0	1	0
Withdrawal by Subject	0	0	1
[1] N=19 randomized on or after 22JAN2008; included in mod. intent-to-treat (MITT) analysis population.

Baseline Characteristics

Arm/Group Title		Sequence: Lidoderm - Placebo - Placebo	Sequence: Placebo - Lidoderm - Lidoderm	Total
Arm/Group Description		Lidoderm (lidocaine 5% patch) 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by matching placebo 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks.	Matching placebo 10cm X 14cm patches each on the front and back of the index knee q24h for 4 weeks followed by Lidoderm (lidocaine 5% patch) 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		50	43	93
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	50 participants	43 participants	93 participants
		61.1 (10.0)	61.1 (10.9)	61.1 (10.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	50 participants	43 participants	93 participants
	Female	32 64.0%	28 65.1%	60 64.5%
	Male	18 36.0%	15 34.9%	33 35.5%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	50 participants	43 participants	93 participants
		50	43	93

Outcome Measures

1. Primary Outcome

Title	Time-to-Exit From Current Study Treatment
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The modified intent-to treat (MITT) population consisted of all intent-to-treat (ITT) patients who were randomized on or after January 22, 2008.

Note: Kaplan-Meier estimates for median time-to-exit from current study treatment could not be calculated for Period 2 or Period 3, because the survival distribution function did not fall below 0.5000.

Arm/Group Title	Sequence: Lidoderm - Placebo - Placebo (LPP)	Sequence: Placebo - Lidoderm - Lidoderm (PLL)
Arm/Group Description:	Lidoderm (lidocaine 5% patch) 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by matching 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks	Matching placebo 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by Lidoderm (lidocaine 5% patch) 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks
Overall Number of Participants Analyzed	21	21
Median (95% Confidence Interval); Unit of Measure: Days
Period 1 ( Sequence LPP, N=21; Sequence PLL, N=21)	31; (10 to 31)	20; (12 to 30)
Period 2 (Sequence LPP, N=19; Sequence PLL, N=20)	NA [1]; (NA to NA)	NA [1]; (NA to NA)
Period 3 (Sequence LPP, N=19; Sequence PLL, N=19)	NA [1]; (19 to NA)	NA [1]; (NA to NA)

[1]

Survival distribution function did not reach 0.5000; ie, patients within the study period did not reach exit criteria by the end of the 4-week period.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence: Lidoderm - Placebo - Placebo (LPP), Sequence: Placebo - Lidoderm - Lidoderm (PLL)
	Comments	The two treatments were compared by time-varying relative hazards, associated P values, and 95% confidence intervals. Appropriate survival or hazard functions were calculated.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1006
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Cox frailty model
	Comments	Model included treatment, sequence, period, and first-order carryover as fixed effects and frailty; patient nested within sequence was frailty.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.78
	Confidence Interval	95%; 0.89 to 3.55
	Estimation Comments	The Hazard Ratio (HR) provided is the ratio of Placebo to Lidoderm.

2. Secondary Outcome

Title	Time-to-Exit Due to Lack of Efficacy
Description	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.
Time Frame	Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks), or Premature Discontinuation

Outcome Measure Data

Analysis Population Description

The modified intent-to treat (MITT) population consisted of all intent-to-treat (ITT) patients who were randomized on or after January 22, 2008.

Note: No patients exited a study period due to lack of efficacy, therefore median time-to-exit could not be calculated.

Arm/Group Title	Sequence: Lidoderm - Placebo - Placebo (LPP)	Sequence: Placebo - Lidoderm - Lidoderm (PLL)
Arm/Group Description:	Lidoderm (Lidocaine 5% Patch) 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by matching 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks	Matching placebo 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by Lidoderm (lidocaine 5% patch) 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks
Overall Number of Participants Analyzed	21	21
Median (95% Confidence Interval); Unit of Measure: days
Period 1 (Sequence LPP, N=21; Sequence PLL, N=21)	NA [1]; (NA to NA)	NA [1]; (NA to NA)
Period 2 (Sequence LPP, N=19; Sequence PLL, N=20)	NA [1]; (NA to NA)	NA [1]; (NA to NA)
Period 3 (Sequence LPP, N=19; Sequence PLL, N=19)	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

No patients discontinued from this study period due to lack of efficacy.

3. Secondary Outcome

Title	Exit Status From Current Study Treatment - Yes
Description	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.
Time Frame	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks), or Premature Discontinuation

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Sequence: Lidoderm - Placebo - Placebo (LPP)	Sequence: Placebo - Lidoderm - Lidoderm (PLL)
Arm/Group Description:	Lidoderm (lidocaine 5% patch) 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by matching 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks	Matching placebo 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by Lidoderm (lidocaine 5% patch) 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks
Overall Number of Participants Analyzed	21	21
Measure Type: Number; Unit of Measure: Participants
Period 1 (Sequence LPP, N=21; Sequence PLL, N=21)	10	12
Period 2 (Sequence LPP, N=19; Sequence PLL, N=20)	5	4
Period 3 (Sequence LPP, N=19; Sequence PLL, N=19)	6	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence: Lidoderm - Placebo - Placebo (LPP), Sequence: Placebo - Lidoderm - Lidoderm (PLL)
	Comments	The proportion of patients who exited from the current treatment period prior to the 4-week planned duration was analyzed using a logistic regression model for repeated measures.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1272
	Comments	The logistic regression model for repeated measures used for this analysis included treatment, sequence, period, and first-order carry-over as fixed effects and repeated measures taken on patients nested within sequence.
	Method	Regression, Logistic
	Comments	The results presented are reported in terms of odds ratios, corresponding 95% confidence intervals, and P-values for each fixed effect in the model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.86
	Confidence Interval	95%; 0.86 to 4.02
	Estimation Comments	The Odds Ratio (OR) provided is the ratio of Lidoderm to Placebo.

4. Secondary Outcome

Title	Overall Treatment Difference in the LSMeans of the Average of the Last Two Daily Pain Intensity Numerical Rating Scale (PI-NRS)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Lidoderm (Lidocaine 5% Patch)	Placebo Patch
Arm/Group Description:	The group represents the pooled data for all patients receiving Lidoderm (lidocaine 5% patch) during the randomized, double-blind treatment period regardless of the randomized study sequence.	The group represents the pooled data for all patients receiving Placebo patches during the randomized, double-blind treatment period regardless of the randomized study sequence.
Overall Number of Participants Analyzed	21	21
Least Squares Mean (Standard Error); Unit of Measure: Units on a scale
	3.03 (0.35)	3.57 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	The overall treatment difference for the lidocaine patch 5% and placebo patch was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0224
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.54
	Confidence Interval	95%; -1.01 to -0.08
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

5. Secondary Outcome

Title	Overall Treatment Difference in the LSMeans of the Average of the Last Two Daily Pain Relief Scale (PRS) Scores
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Lidoderm (Lidocaine 5% Patch)	Placebo Patch
Arm/Group Description:	The group represents the pooled data for all patients receiving Lidoderm (lidocaine 5% patch) during the randomized, double-blind treatment period regardless of the randomized study sequence.	The group represents the pooled data for all patients receiving placebo patches during the randomized, double-blind treatment period regardless of the randomized study sequence.
Overall Number of Participants Analyzed	21	21
Least Squares Mean (Standard Error); Unit of Measure: Units on a scale
	4.45 (0.25)	4.06 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	The overall treatment difference for the lidocaine patch 5% and placebo patch was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2747
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects regression
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.39
	Confidence Interval	95%; -0.31 to 1.09
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

6. Secondary Outcome

Title	Overall Treatment Difference of the LSMeans of the Pain Quality Assessment Scale (PQAS) Scores
Description	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.
Time Frame	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Lidoderm (Lidocaine 5% Patch)	Placebo Patch
Arm/Group Description:	The group represents the pooled data for all patients receiving Lidoderm (lidocaine 5% patch) during the randomized, double-blind treatment period regardless of the randomized study sequence.	The group represents the pooled data for all patients receiving placebo patches during the randomized, double-blind treatment period regardless of the randomized study sequence.
Overall Number of Participants Analyzed	21	21
Least Squares Mean (Standard Error); Unit of Measure: Units on a scale
Intense	3.31 (0.32)	3.53 (0.32)
Sharp	2.50 (0.34)	3.00 (0.34)
Hot	1.12 (0.26)	1.59 (0.27)
Dull	3.04 (0.33)	3.28 (0.33)
Cold	0.62 (0.14)	0.50 (0.14)
Sensitive	0.88 (0.20)	0.96 (0.21)
Tender	2.08 (0.30)	1.89 (0.30)
Itchy	0.90 (0.23)	1.00 (0.23)
Shocking	1.95 (0.34)	2.36 (0.34)
Numb	1.31 (0.28)	1.52 (0.28)
Electrical	1.32 (0.29)	1.26 (0.30)
Tingling	1.24 (0.26)	1.24 (0.26)
Cramping	1.78 (0.33)	2.03 (0.33)
Radiating	2.03 (0.35)	2.10 (0.35)
Throbbing	2.24 (0.34)	2.06 (0.35)
Aching	2.78 (0.36)	3.22 (0.37)
Heavy	2.12 (0.34)	2.26 (0.34)
Overall unpleasantness	2.98 (0.34)	3.55 (0.35)
Intense deep pain	3.33 (0.37)	3.77 (0.37)
Intense surface pain	1.61 (0.28)	1.82 (0.29)
Average surface pain	0.99 (0.15)	1.05 (0.15)
Average deep pain	2.38 (0.29)	2.55 (0.29)
Average paroxysmal pain	1.78 (0.25)	2.06 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Intense: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4498
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.22
	Confidence Interval	95%; -0.80 to 0.36
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Sharp: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1065
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effect models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.50
	Confidence Interval	95%; -1.11 to 0.11
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch)
	Comments	Hot: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0484
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.47
	Confidence Interval	95%; -0.94 to -0.00
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch)
	Comments	Dull: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4973
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effect models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.24
	Confidence Interval	95%; -0.93 to 0.46
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Cold: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3966
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effect models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.12
	Confidence Interval	95%; -0.16 to 0.41
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Sensitive: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6941
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.09
	Confidence Interval	95%; -0.53 to 0.35
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Tender: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5664
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.18
	Confidence Interval	95%; -0.45 to 0.82
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Itchy: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6871
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.09
	Confidence Interval	95%; -0.55 to 0.37
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Shocking: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2318
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.41
	Confidence Interval	95%; -1.08 to 0.27
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Numb: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3383
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.21
	Confidence Interval	95%; -0.64 to 0.22
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Electrical: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8740
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.05
	Confidence Interval	95%; -0.63 to 0.73
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Tingling: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9990
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.00
	Confidence Interval	95%; -0.54 to 0.54
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Cramping: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4183
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.25
	Confidence Interval	95%; -0.85 to 0.36
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Radiating: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8227
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.07
	Confidence Interval	95%; -0.71 to 0.57
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Throbbing: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5870
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.18
	Confidence Interval	95%; -0.48 to 0.85
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Aching: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2181
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.44
	Confidence Interval	95%; -1.15 to 0.27
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Heavy: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6276
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.13
	Confidence Interval	95%; -0.68 to 0.42
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Overall unpleasantness: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0917
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.57
	Confidence Interval	95%; -1.23 to 0.09
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Intense deep pain: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2089
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.44
	Confidence Interval	95%; -1.13 to 0.25
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Intense surface pain: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4188
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.22
	Confidence Interval	95%; -0.75 to 0.31
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Average surface pain: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6959
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.05
	Confidence Interval	95%; -0.32 to 0.21
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Average deep pain: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4806
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.17
	Confidence Interval	95%; -0.64 to 0.30
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Average paroxysmal pain: the difference between Lidoderm and placebo was compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2291
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.28
	Confidence Interval	95%; -0.74 to 0.18
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

7. Secondary Outcome

Title	Patient Global Impression of Change From Baseline in Osteoarthritis (OA) Pain
Description	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).
Time Frame	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Sequence: Lidoderm - Placebo - Placebo (LPP)	Sequence: Placebo - Lidoderm - Lidoderm (PLL)
Arm/Group Description:	Lidoderm (lidocaine 5% patch) 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by matching 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks	Matching placebo 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by Lidoderm (lidocaine 5% patch) 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks
Overall Number of Participants Analyzed	21	21
Measure Type: Number; Unit of Measure: Participants
6-Very Much Impr, Period 1 (LPP, N=21; PLL, N=21)	3	5
6-Very Much Impr., Period 2 (LPP, N=19; PLL, N=20)	3	2
6-Very Much Impr., Period 3 (LPP, N=19; PLL, N=19)	4	4
5-Much Improved, Period 1 (LPP, N=21; PLL, N=21)	6	8
5-Much Improved, Period 2 (LPP, N=19; PLL, N=20)	9	8
5-Much Improved, Period 3 (LPP, N=19; PLL, N=19)	8	10
4-Mini. Improved, Period 1 (LPP, N=21; PLL, N=21)	7	4
4-Mini. Improved, Period 2 (LPP, N=19; PLL, N=20)	3	6
4-Mini. Improved, Period 3 (LPP, N=19; PLL, N=19)	3	3
3-No Change, Period 1 (LPP, N=21; PLL, N=21)	5	1
3-No Change, Period 2 (LPP, N=19; PLL, N=20)	1	2
3-No Change, Period 3 (LPP, N=19; PLL, N=19)	4	2
2-Minimally Worse, Period 1 (LPP, N=21; PLL,N=19)	0	3
2-Minimally Worse, Period 2 (LPP, N=19; PLL, N=20)	1	1
2-Minimally Worse, Period 3 (LPP, N=19; PLL, N=19)	0	0
1-Much Worse, Period 1 (LPP, N=21; PLL, N=21)	0	0
1-Much Worse, Period 2 (LPP, N=19; PLL, N=20)	2	0
1-Much Worse, Period 3 (LPP, N=19; PLL, N=19)	0	0
0-Very Much Worse, Period 1 (LPP,N=21; PLL, N=21)	0	0
0-Very Much Worse, Period 2 (LPP, N=19; PLL, N=20)	0	1
0-Very Much Worse, Period 3 (LPP, N=19; PLL, N=19)	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence: Lidoderm - Placebo - Placebo (LPP), Sequence: Placebo - Lidoderm - Lidoderm (PLL)
	Comments	Global impression of change from baseline with the lidocaine patch 5% and placebo patch were compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. An ordinal multinomial regression model was performed with sequence, period, treatment, carry over effect as fixed effects, with repeated measures taken on patient within sequence.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3185
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.32
	Confidence Interval	95%; 0.77 to 2.27
	Estimation Comments	The Odds Ratio (OR) provided is the ratio of Lidoderm to Placebo.

8. Secondary Outcome

Title	Investigator Global Impression of Change From Baseline in Osteoarthritis (OA) Pain
Description	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.
Time Frame	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Sequence: Lidoderm - Placebo - Placebo (LPP)	Sequence: Placebo - Lidoderm - Lidoderm (PLL)
Arm/Group Description:	Lidoderm (lidocaine 5% patch) 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by matching 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks	Matching placebo 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by Lidoderm (lidocaine 5% patch) 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks
Overall Number of Participants Analyzed	21	21
Measure Type: Number; Unit of Measure: Participants
6-Very Much Impr, Period 1 (LPP, N=21; PLL, N=21)	3	4
6-Very Much Impr, Period 2 (LPP, N=19; PLL, N=20)	2	3
6-Very Much Impr, Period 3 (LPP, N=19; PLL, N=19)	5	4
5-Much Improved, Period 1 (LPP, N=21; PLL, N=21)	7	9
5-Much Improved, Period 2 (LPP, N=19; PLL, N=20)	10	8
5-Much Improved, Period 3 (LPP, N=19; PLL, N=19)	7	8
4-Min. Improved, Period 1 (LPP, N=21; PLL, N=21)	4	2
4-Min. Improved, Period 2 (LPP, N=19; PLL, N=20)	3	7
4-Min. Improved, Period 3 (LPP, N=19; PLL, N=19)	4	4
3-No Change, Period 1 (LPP, N=21; PLL, N=21)	3	2
3-No Change, Period 2 LPP, N=19; PLL, N=20)	0	1
3-No Change, Period 3 (LPP, N=19; PLL, N=19)	1	2
2-Minimally Worse, Period 1 (LPP, N=21; PLL, N=21)	3	3
2-Minimally Worse, Period 2 (LPP, N=19; PLL, N=20)	1	0
2-Minimally Worse, Period 3 (LPP, N=19; PLL, N=19)	0	1
1-Much Worse, Period 1 (LPP, N=21; PLL, N=21)	1	1
1-Much Worse, Period 2 (LPP, N=19; PLL, N=20)	3	0
1-Much Worse, Period 3 (LPP, N=19; PLL, N=19)	1	0
0-Very Much Worse, Period 1 (LPP, N=21; PLL, N=21)	0	0
0-Very Much Worse, Period 2 (LPP, N=19; PLL, N=20)	0	1
0-Very Much Worse, Period 3 (LPP, N=19; PLL, N=19)	1	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence: Lidoderm - Placebo - Placebo (LPP), Sequence: Placebo - Lidoderm - Lidoderm (PLL)
	Comments	Global impression of change from baseline with the lidocaine patch 5% and placebo patch were compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. An ordinal multinomial regression model was performed with sequence, period, treatment, carry over effect as fixed effects, with repeated measures taken on patient within sequence.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4748
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.22
	Confidence Interval	95%; 0.72 to 2.06
	Estimation Comments	The odds ratio (OR) provided is the ratio of Lidoderm to Placebo.

9. Secondary Outcome

Title	Patient Global Assessment of Treatment Satisfaction
Description	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.
Time Frame	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Sequence: Lidoderm - Placebo - Placebo (LPP)	Sequence: Placebo - Lidoderm - Lidoderm (PLL)
Arm/Group Description:	Lidoderm (lidocaine 5% patch) 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by matching 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks	Matching placebo 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by Lidoderm (lidocaine 5% patch) 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks
Overall Number of Participants Analyzed	21	21
Measure Type: Number; Unit of Measure: Participants
4-Very Satisfied, Period 1 (LPP, N=21; PLL, N=21)	12	9
4-Very Satisfied, Period 2 (LPP, N=19; PLL, N=20)	8	10
4-Very Satisfied, Period 3 (LPP, N=19; PLL, N=20)	12	12
3-Satisfied, Period 1 (LPP, N=21; PLL, N=21)	7	8
3-Satisfied, Period 2 (LPP, N=19; PLL, N=20)	9	6
3-Satisfied, Period 3 (LPP, N=19; PLL, N=20)	5	6
2-No Preference, Period 1 (LPP, N=21; PLL, N=21)	1	3
2-No Preference, Period 2 (LPP, N=19; PLL, N=20)	0	3
2-No Preference, Period 3 (LPP, N=19; PLL, N=20)	1	1
1-Dissatisfied, Period 1 (LPP, N=21; PLL, N=21)	1	1
1-Dissatisfied, Period 2 (LPP, N=19; PLL, N=20)	2	0
1-Dissatisfied, Period 3 (LPP, N=19; PLL, N=20)	0	0
0-Very Dissatisfied, Per. 1 (LPP, N=21; PLL, N=21)	0	0
0-Very Dissatisfied, Per. 2 (LPP, N=19; PLL, N=20)	0	1
0-Very Dissatisfied, Per. 3 (LPP, N=19; PLL, N=19)	1	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence: Lidoderm - Placebo - Placebo (LPP), Sequence: Placebo - Lidoderm - Lidoderm (PLL)
	Comments	Treatment satisfaction with the lidocaine patch 5% and placebo patch were compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. An ordinal multinomial regression model was performed with sequence, period, treatment, carry over effect as fixed effects, with repeated measures taken on patient within sequence.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2605
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.71
	Confidence Interval	95%; 0.38 to 1.30
	Estimation Comments	The odds ratio (OR) provided is the ratio of Lidoderm to Placebo.

10. Secondary Outcome

Title	Investigator Global Assessment of Treatment Satisfaction
Description	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).
Time Frame	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Sequence: Lidoderm - Placebo - Placebo (LPP)	Sequence: Placebo - Lidoderm - Lidoderm (PLL)
Arm/Group Description:	Lidoderm (lidocaine 5% patch) 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by matching 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks	Matching placebo 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by Lidoderm (lidocaine 5% patch) 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks
Overall Number of Participants Analyzed	21	21
Measure Type: Number; Unit of Measure: Participants
4-Very Satisfied, Period 1 (LPP, N=21; PLL,N=21)	7	6
4-Very Satisfied, Period 2 (LPP, N=19; PLL, N=20)	5	8
4-Very Satisfied, Period 3 (LPP, N=19; PLL, N=19)	8	11
3-Satisfied, Period 1 (LPP, N=21; PLL,N=21)	8	9
3-Satisfied, Period 2 (LPP, N=19; PLL, N=20)	11	10
3-Satisfied, Period 3 (LPP, N=19; PLL, N=19)	9	5
2-No Preference, Period 1 (LPP, N=21; PLL,N=21)	1	1
2-No Preference, Period 2 (LPP, N=19; PLL, N=20)	1	1
2-No Preference, Period 3 (LPP, N=19; PLL, N=19)	1	2
1-Dissatisfied, Period 1 (LPP, N=21; PLL,N=21)	4	5
1-Dissatisfied, Period 2 (LPP, N=19; PLL, N=20)	2	0
1-Dissatisfied, Period 3 (LPP, N=19; PLL, N=19)	0	1
0-Very Dissatisfied, Period 1 (LPP,N=21; PLL,N=21)	1	0
0-Very Dissatisfied, Period 2 (LPP,N=19; PLL,N=20)	0	1
0-Very Dissatisfied, Period 3 (LPP,N=19; PLL,N=19)	1	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence: Lidoderm - Placebo - Placebo (LPP), Sequence: Placebo - Lidoderm - Lidoderm (PLL)
	Comments	Treatment satisfaction with the lidocaine patch 5% and placebo patch were compared by combining data for patients receiving the respective treatment regardless of the randomized study sequence. An ordinal multinomial regression model was performed with sequence, period, treatment, carry over effect as fixed effects, with repeated measures taken on patient within sequence.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3193
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.76
	Confidence Interval	95%; 0.44 to 1.30
	Estimation Comments	The odds ratio (OR) provided is the ratio of Lidoderm to Placebo.

11. Other Pre-specified Outcome

Title	Overall Treatment Difference in LSMeans of Beck Depression Inventory Second Edition (BDI-II) Total Score
Description	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.
Time Frame	Baseline and end of treatment period (up to 4 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Lidoderm (Lidocaine 5% Patch)	Placebo Patch
Arm/Group Description:	The group represents the pooled data for all patients receiving Lidoderm (lidocaine 5% patch) during the randomized, double-blind treatment period regardless of the randomized study sequence.	The group represents the pooled data for all patients receiving placebo patches during the randomized, double-blind treatment period regardless of the randomized study sequence.
Overall Number of Participants Analyzed	21	21
Least Squares Mean (Standard Error); Unit of Measure: Units on a scale
	4.41 (0.39)	4.29 (0.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	The overall treatment difference for the lidocaine patch 5% and placebo patch was compared by combining data for patients receiving the respective treatment regardless of randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7839
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.12
	Confidence Interval	95%; -0.74 to 0.98
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

12. Other Pre-specified Outcome

Title	Quality of Life: Four Category Beck Depression Inventory Second Edition (BDI-II) Composite Score
Description	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.
Time Frame	Screening, Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Sequence: Lidoderm - Placebo - Placebo (LPP)	Sequence: Placebo - Lidoderm - Lidoderm (PLL)
Arm/Group Description:	Lidoderm (lidocaine 5% patch) 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by matching placebo 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks	Matching placebo 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by Lidoderm (lidocaine 5% patch) 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks
Overall Number of Participants Analyzed	21	21
Measure Type: Number; Unit of Measure: Participants
Minimal at Screening (LPP, N=21; PLL, N=21)	21	20
Minimal at Baseline (LPP, N=21; PLL, N=21)	21	20
Minimal, end of Period 1 (LPP, N=21; PLL, N=21)	21	19
Minimal, end of Period 2 (LPP, N=19; PLL, N=20)	19	20
Minimal, end of Period 3 (LPP, N=19; PLL, N=19)	19	19
Mild at Screening (LPP, N=21; PLL, N=21)	0	1
Mild at Baseline (LPP, N=21; PLL, N=21)	0	1
Mild, end of Period 1 (LPP, N=21; PLL, N=21)	0	1
Mild, end of Period 2 (LPP, N=19; PLL, N=20)	0	0
Mild, end of Period 3 (LPP, N=19; PLL, N=19)	0	0
Moderate at Screening (LPP, N=21; PLL, N=21)	0	0
Moderate at Baseline (LPP, N=21; PLL, N=21)	0	0
Moderate, end of Period 1 (LPP, N=21; PLL, N=21)	0	1
Moderate, end of Period 2 (LPP, N=19; PLL, N=20)	0	0
Moderate, end of Period 3 (LPP, N=19; PLL, N=19)	0	0
Severe at Screening (LPP, N=21; PLL, N=21)	0	0
Severe at Baseline (LPP, N=21; PLL, N=21)	0	0
Severe, end of Period 1 (LPP, N=21; PLL, N=21)	0	0
Severe, end of Period 2 (LPP, N=19; PLL, N=20)	0	0
Severe, end of Period 3 (LPP, N=19; PLL, N=19)	0	0

13. Other Pre-specified Outcome

Title	Overall Treatment Difference in LSMeans for Continuous EuroQol Quality of Life Instrument (EQ-5D) Index Scores
Description	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).
Time Frame	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks), or Premature Discontinuation

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Lidoderm (Lidocaine 5% Patch)	Placebo Patch
Arm/Group Description:	The group represents the pooled data for all patients receiving Lidoderm (lidocaine 5% patch) during the randomized, double-blind treatment period regardless of the randomized study sequence.	The group represents the pooled data for all patients receiving placebo patches during the randomized, double-blind treatment period regardless of the randomized study sequence.
Overall Number of Participants Analyzed	21	21
Least Squares Mean (Standard Error); Unit of Measure: Units on a scale
	0.82 (0.01)	0.81 (0.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	The overall treatment difference for the lidocaine patch 5% and placebo patch was compared by combining data for patients receiving the respective treatment regardless of randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3773
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.01
	Confidence Interval	95%; -0.02 to 0.04
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

14. Other Pre-specified Outcome

Title	Overall Treatment Difference in LSMeans for Continuous EuroQol Quality of Life Instrument (EQ-5D) Health Status Today Using a Visual Analog Scale (VAS)
Description	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).
Time Frame	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks), or Premature Discontinuation

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Lidoderm (Lidocaine 5% Patch)	Placebo Patch
Arm/Group Description:	The group represents the pooled data for all patients receiving Lidoderm (lidocaine 5% patch) during the randomized, double-blind treatment period regardless of the randomized study sequence.	The group represents the pooled data for all patients receiving placebo patches during the randomized, double-blind treatment period regardless of the randomized study sequence.
Overall Number of Participants Analyzed	21	21
Least Squares Mean (Standard Error); Unit of Measure: Units on a scale
	81.1 (1.25)	79.4 (1.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	The overall treatment difference for the lidocaine patch 5% and placebo patch was compared by combining data for patients receiving the respective treatment regardless of randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1378
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.74
	Confidence Interval	95%; -0.57 to 4.04
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

15. Other Pre-specified Outcome

Title	Quality of Life: Three-Category EuroQol Quality of Life Instrument (EQ-5D) General Health Today Compared to Last 12 Months
Description	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.
Time Frame	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks), or Premature Discontinuation

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Sequence: Lidoderm - Placebo - Placebo (LPP)	Sequence: Placebo - Lidoderm - Lidoderm (PLL)
Arm/Group Description:	Lidoderm (lidocaine 5% patch) 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by matching placebo 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks	Matching placebo 10cm X 14cm patches each on the front and back of the index knee every 24 hours (q24h) for 4 weeks followed by Lidoderm (lidocaine 5% patch) 10cm x 14cm patches each on the front and back of the index knee q24h for up to 8 weeks
Overall Number of Participants Analyzed	21	21
Measure Type: Number; Unit of Measure: Participants
Better Baseline (LPP, N=21; PLL, N=21)	11	4
Better Period 1 (LPP, N=21; PLL, N=21)	7	5
Better Period 2 (LPP, N=19; PLL, N=20)	8	4
Better Period 3 (LPP, N=19; PLL, N=19)	9	6
Much the Same Baseline (LPP, N=21; PLL, N=21)	10	17
Much the Same Period 1 (LPP, N=21; PLL, N=21)	14	15
Much the Same Period 2 (LPP, N=19; PLL, N=20)	10	16
Much the Same Period 3 (LPP, N=19; PLL, N=19)	9	12
Worse Baseline (LPP, N=21; PLL, N=21)	0	0
Worse Period 1 (LPP, N=21; PLL, N=21)	0	1
Worse Period 2 (LPP, N=19; PLL, N=20)	1	0
Worse Period 3 (LPP, N=19; PLL, N=19)	0	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence: Lidoderm - Placebo - Placebo (LPP), Sequence: Placebo - Lidoderm - Lidoderm (PLL)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6833
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Regression, Logistic
	Comments	An ordinal multinomial regression model was performed with sequence, period, treatment, carry over effect as fixed effects.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.88
	Confidence Interval	95%; 0.47 to 1.65
	Estimation Comments	The Odds Ratio (OR) provided is the ratio of Lidoderm to Placebo.

16. Other Pre-specified Outcome

Title	Overall Treatment Difference in LSMeans for Verran Snyder-Halpern (VSH) Sleep Scale
Description	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.
Time Frame	Baseline, Period 1 (up to 4 weeks), Period 2 (up to 4 weeks), Period 3 (up to 4 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (MITT) population consisted of all intent-to-treat (ITT) patients defined as all patients who received study medication and provided run-in and baseline assessments and had at least 1 post-baseline efficacy assessment and who were randomized on or after January 22, 2008.

Arm/Group Title	Lidoderm (Lidocaine 5% Patch)	Placebo Patch
Arm/Group Description:	The group represents the pooled data for all patients receiving Lidoderm (lidocaine 5% patch) during the randomized, double-blind treatment period regardless of the randomized study sequence.	The group represents the pooled data for all patients receiving placebo patches during the randomized, double-blind treatment period regardless of the randomized study sequence.
Overall Number of Participants Analyzed	21	21
Least Squares Mean (Standard Error); Unit of Measure: Units on a scale
Disturbance	246 (13.7)	224 (13.9)
Effectiveness	303 (9.69)	302 (9.85)
Supplementation	49.7 (7.62)	41.4 (7.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Disturbance: the overall treatment difference for Lidoderm and placebo patch was compared by combining data for patients receiving the respective treatment regardless of randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1143
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	22.16
	Confidence Interval	95%; -5.48 to 49.8
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Effectiveness: the overall treatment difference for Lidoderm and placebo patch was compared by combining data for patients receiving the respective treatment regardless of randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9108
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.18
	Confidence Interval	95%; -19.8 to 22.2
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lidoderm (Lidocaine 5% Patch), Placebo Patch
	Comments	Supplementation: the overall treatment difference for Lidoderm and placebo patch was compared by combining data for patients receiving the respective treatment regardless of randomized study sequence. The endpoint was analyzed by linear mixed effects models incorporating treatment, period, sequence, and first-order carryover as fixed effects, and patient nested within sequence as a random effect. P-value for the random effect (s2) is from the Wald Z-test for the covariance parameter estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3769
	Comments	All statistical tests were 2-sided with a significance level of alpha=0.05.
	Method	Linear mixed effects models
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.31
	Confidence Interval	95%; -10.3 to 27.0
	Estimation Comments	The results are reported as least squares means and their differences along with associated P-values, and 95% confidence intervals for each fixed effect in the model.

Adverse Events

Time Frame	All adverse events (AEs) were recorded from the beginning of the active Run-in Period through 30 days post-study completion/early termination; a period lasting up to 20 weeks in total.
Adverse Event Reporting Description	The safety population included all patients who received study medication during the study and did not return all study medication unopened.
Arm/Group Title	Run-In Period With Lidoderm (Lidocaine 5% Patch)	Double-Blind Treatment Period With Lidoderm	Double-Blind Active Treatment Period With Placebo
Arm/Group Description	Treatment-Emergent Adverse Events (TEAEs) reported by subjects on Lidoderm (lidocaine 5% patch) during the active treatment Run-in Period. A treatment-emergent AE (TEAE) is any condition that was not present prior to treatment with study medication, but appeared following treatment, was present at treatment initiation, but worsened during treatment, or was present at treatment initiation, but resolved and then reappeared while the individual was on treatment (regardless of the intensity of the AE when the treatment was initiated).	Treatment-Emergent Adverse Events (TEAEs) reported by subjects on Lidoderm (lidocaine 5% patch) during the Double-blind Treatment Period. A treatment-emergent AE (TEAE) is any condition that was not present prior to treatment with study medication, but appeared following treatment, was present at treatment initiation, but worsened during treatment, or was present at treatment initiation, but resolved and then reappeared while the individual was on treatment (regardless of the intensity of the AE when the treatment was initiated). *NOTE: two subjects randomized to the treatment sequence Placebo - Lidoderm - Lidoderm (PLL) discontinued from the study during treatment with Placebo (Period 1); therefore, the number of subjects included in the safety analysis by treatment group (Lidoderm) is equal to 91.	Treatment-Emergent Adverse Events (TEAEs) reported by subjects on Placebo during the Double-blind Treatment Period. A treatment-emergent AE (TEAE) is any condition that was not present prior to treatment with study medication, but appeared following treatment, was present at treatment initiation, but worsened during treatment, or was present at treatment initiation, but resolved and then reappeared while the individual was on treatment (regardless of the intensity of the AE when the treatment was initiated). **NOTE: two subjects randomized to the treatment sequence Lidoderm - Placebo - Placebo (PLL) discontinued from the study during treatment with Lidoderm (Period 1); therefore, the number of subjects included in the safety analysis by treatment group (Placebo) is equal to 91.
All-Cause Mortality
	Run-In Period With Lidoderm (Lidocaine 5% Patch)	Double-Blind Treatment Period With Lidoderm	Double-Blind Active Treatment Period With Placebo
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Run-In Period With Lidoderm (Lidocaine 5% Patch)	Double-Blind Treatment Period With Lidoderm	Double-Blind Active Treatment Period With Placebo
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/169 (0.59%)	1/91 (1.10%)	1/91 (1.10%)
Cardiac disorders
Supraventricular extrasystoles * 1	0/169 (0.00%)	1/91 (1.10%)	0/91 (0.00%)
Infections and infestations
Pneumonia * 1	1/169 (0.59%)	0/91 (0.00%)	1/91 (1.10%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (Unspecified)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0.5%
	Run-In Period With Lidoderm (Lidocaine 5% Patch)	Double-Blind Treatment Period With Lidoderm	Double-Blind Active Treatment Period With Placebo
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	51/169 (30.18%)	24/91 (26.37%)	23/91 (25.27%)
Blood and lymphatic system disorders
Anaemia * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Cardiac disorders
Coronary artery disease * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Sinus bradycardia * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Bradycardia * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Palpitations * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Sinus tachycardia * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Ear and labyrinth disorders
Eustachian tube dysfunction * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Vertigo * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Eye disorders
Dry eye * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Gastrointestinal disorders
Constipation * 1	2/169 (1.18%)	1/91 (1.10%)	0/91 (0.00%)
Diarrhoea * 1	2/169 (1.18%)	0/91 (0.00%)	2/91 (2.20%)
Gastritis * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Nausea * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Stomach discomfort * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Vomiting * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
General disorders
Application site dermatitis * 1	2/169 (1.18%)	0/91 (0.00%)	0/91 (0.00%)
Application site erythema * 1	2/169 (1.18%)	1/91 (1.10%)	2/91 (2.20%)
Oedema peripheral * 1	2/169 (1.18%)	1/91 (1.10%)	0/91 (0.00%)
Pain * 1	2/169 (1.18%)	0/91 (0.00%)	0/91 (0.00%)
Pyrexia * 1	2/169 (1.18%)	0/91 (0.00%)	0/91 (0.00%)
Application site reaction * 1	1/169 (0.59%)	4/91 (4.40%)	1/91 (1.10%)
Application site oedema * 1	0/169 (0.00%)	1/91 (1.10%)	0/91 (0.00%)
Application site swelling * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Application site vesicles * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Fatigue * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Immune system disorders
Hypersensitivity * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Seasonal allergy * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Infections and infestations
Nasopharyngitis * 1	3/169 (1.78%)	2/91 (2.20%)	3/91 (3.30%)
Sinusitis * 1	2/169 (1.18%)	2/91 (2.20%)	3/91 (3.30%)
Upper respiratory tract infection * 1	1/169 (0.59%)	2/91 (2.20%)	0/91 (0.00%)
Bronchitis * 1	0/169 (0.00%)	1/91 (1.10%)	1/91 (1.10%)
Pneumonia * 1	0/169 (0.00%)	1/91 (1.10%)	0/91 (0.00%)
Cellulitis * 1	1/169 (0.59%)	1/91 (1.10%)	1/91 (1.10%)
Ear infection * 1	0/169 (0.00%)	1/91 (1.10%)	0/91 (0.00%)
Gastrointestinal infection * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Keratitis herpetic * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Otitis media * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Vaginal candidiasis * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Influenza * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Pharyngitis * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Urinary tract infection * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Injury, poisoning and procedural complications
Contusion * 1	2/169 (1.18%)	0/91 (0.00%)	0/91 (0.00%)
Arthropod sting * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Excoriation * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Hand fracture * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Joint dislocation * 1	0/169 (0.00%)	1/91 (1.10%)	0/91 (0.00%)
Upper limb fracture * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Burns first degree * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Joint injury * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Investigations
Blood potassium decreased * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	2/169 (1.18%)	0/91 (0.00%)	0/91 (0.00%)
Chest wall pain * 1	2/169 (1.18%)	1/91 (1.10%)	0/91 (0.00%)
Neck pain * 1	0/169 (0.00%)	1/91 (1.10%)	1/91 (1.10%)
Arthropathy * 1	0/169 (0.00%)	1/91 (1.10%)	0/91 (0.00%)
Back pain * 1	1/169 (0.59%)	0/91 (0.00%)	1/91 (1.10%)
Muscle spasms * 1	0/169 (0.00%)	1/91 (1.10%)	0/91 (0.00%)
Musculoskeletal stiffness * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Shoulder pain * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Tendonitis * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroma * 1	0/169 (0.00%)	1/91 (1.10%)	0/91 (0.00%)
Nervous system disorders
Headache * 1	3/169 (1.78%)	1/91 (1.10%)	0/91 (0.00%)
Dizziness * 1	2/169 (1.18%)	0/91 (0.00%)	0/91 (0.00%)
Carpal tunnel syndrome * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Hypoaesthesia * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Paraesthesia * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Burning sensation * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Psychiatric disorders
Agitation * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Anger * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Depression * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Renal and urinary disorders
Renal cyst * 1	0/169 (0.00%)	1/91 (1.10%)	0/91 (0.00%)
Renal failure * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Haematuria * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Reproductive system and breast disorders
Dysmenorrhoea * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion * 1	2/169 (1.18%)	0/91 (0.00%)	0/91 (0.00%)
Dyspnoea * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Haemoptysis * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Productive cough * 1	1/169 (0.59%)	1/91 (1.10%)	0/91 (0.00%)
Sinus congestion * 1	0/169 (0.00%)	1/91 (1.10%)	0/91 (0.00%)
Cough * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Rales * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Respiratory tract congestion * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Skin and subcutaneous tissue disorders
Erythema * 1	2/169 (1.18%)	1/91 (1.10%)	0/91 (0.00%)
Pruritus * 1	2/169 (1.18%)	0/91 (0.00%)	0/91 (0.00%)
Rash * 1	2/169 (1.18%)	0/91 (0.00%)	1/91 (1.10%)
Pruritus generalised * 1	0/169 (0.00%)	1/91 (1.10%)	0/91 (0.00%)
Skin irritation * 1	0/169 (0.00%)	0/91 (0.00%)	1/91 (1.10%)
Nail pigmentation * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Psoriasis * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
Vascular disorders
Hypertension * 1	1/169 (0.59%)	1/91 (1.10%)	0/91 (0.00%)
Peripheral coldness * 1	1/169 (0.59%)	0/91 (0.00%)	0/91 (0.00%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (Unspecified)

Limitations and Caveats

Due to operational issues, the modified intent-to-treat (MITT) population, consisting of all intent-to-treat (ITT) patients randomized on or after January 22, 2008, was added to the analysis plan; all efficacy data are presented for this population.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Delay of 12-18 months from Completion Date to publish results from all sites, embargo of 60 to 180 days from the time communication is submitted to sponsor, and ability to redact confidential information (excluding results).

Results Point of Contact

Name/Title: Clinical Trial Coordinator

Organization: Endo Pharmaceuticals, Inc.

Phone: Use e-mail contact

EMail: clinicalsite.inquiries@endo.com

Responsible Party:	Endo Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00589979 History of Changes
Other Study ID Numbers:	EN3260-003
First Submitted:	December 26, 2007
First Posted:	January 10, 2008
Results First Submitted:	December 22, 2009
Results First Posted:	September 22, 2010
Last Update Posted:	October 5, 2017