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Trial record 5 of 453 for:    applied AND ointment

A Study to Evaluate the Safety and Efficacy of Topically Applied TV 45070 Ointment in Patients With Postherpetic Neuralgia (PHN) ((PHN))

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02365636
Recruitment Status : Completed
First Posted : February 19, 2015
Results First Posted : October 23, 2018
Last Update Posted : October 23, 2018
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Postherpetic Neuralgia
Interventions Drug: TV-45070
Drug: Placebo
Enrollment 300
Recruitment Details 658 patients with chronic postherpetic neuralgia (PHN) were screened; reasons for not enrolling included: inclusion criteria not met (144), exclusion criteria met (171), consent withdrawn (28), lost to follow-up (6), adverse event (1), other (8).
Pre-assignment Details 300 participants were randomly assigned in a 1:1:1 ratio to 1 of 3 treatment groups.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28. TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28. Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Period Title: Overall Study
Started 100 100 100
Safety Population 100 98 [1] 100
Full Analysis Set 100 98 100
Completed 94 93 97
Not Completed 6 7 3
Reason Not Completed
Adverse Event             3             3             2
Protocol Violation             1             4             0
Lost to Follow-up             0             0             1
Not specified             2             0             0
[1]
2 terminated prior to treatment due to 1) prohibited concomitant medication 2) exclusion criteria
Arm/Group Title TV-45070 4% TV-45070 8% Placebo Total
Hide Arm/Group Description TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28. TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28. Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28. Total of all reporting groups
Overall Number of Baseline Participants 100 100 100 300
Hide Baseline Analysis Population Description
Intent to treat population
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 100 participants 100 participants 100 participants 300 participants
57.2  (15.99) 57.6  (16.61) 58.6  (15.80) 57.8  (16.09)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 100 participants 300 participants
Female
57
  57.0%
50
  50.0%
65
  65.0%
172
  57.3%
Male
43
  43.0%
50
  50.0%
35
  35.0%
128
  42.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 100 participants 300 participants
Hispanic or Latino
56
  56.0%
53
  53.0%
70
  70.0%
179
  59.7%
Not Hispanic or Latino
43
  43.0%
47
  47.0%
30
  30.0%
120
  40.0%
Unknown or Not Reported
1
   1.0%
0
   0.0%
0
   0.0%
1
   0.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 100 participants 300 participants
White
81
  81.0%
79
  79.0%
90
  90.0%
250
  83.3%
Black or African American
13
  13.0%
17
  17.0%
7
   7.0%
37
  12.3%
Asian
3
   3.0%
3
   3.0%
1
   1.0%
7
   2.3%
American Indian or Alaskan Native
1
   1.0%
1
   1.0%
1
   1.0%
3
   1.0%
Other
2
   2.0%
0
   0.0%
1
   1.0%
3
   1.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 100 participants 100 participants 100 participants 300 participants
77.02  (13.775) 77.41  (13.383) 77.86  (15.111) 77.43  (14.066)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 100 participants 100 participants 100 participants 300 participants
167.27  (10.258) 168.03  (8.203) 165.82  (10.355) 167.04  (9.668)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 100 participants 100 participants 100 participants 300 participants
27.42  (3.457) 27.30  (3.452) 28.15  (3.798) 27.62  (3.580)
R1150W Polymorphism Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 100 participants 300 participants
Homozygous minor allele (positive, AA)
1
   1.0%
2
   2.0%
0
   0.0%
3
   1.0%
Heterozygous (positive, AG)
17
  17.0%
25
  25.0%
22
  22.0%
64
  21.3%
Homozygous common allele (negative, GG)
82
  82.0%
73
  73.0%
78
  78.0%
233
  77.7%
[1]
Measure Description: Patients who carry the R1150W polymorphism have a nucleotide containing adenine (A) instead of guanine (G) in the rs6746030 single nucleotide polymorphism in the SCN9A gene. This change causes an arginine to tryptophan amino acid residue change at position 1150 in the alpha subunit of the voltage-gated sodium channel NaV1.7. Those who carry the R1150W polymorphism may be heterozygous (GA) or homozygous (AA) for the minor allele. This R1150W polymorphism in the SCN9A gene may affect pain perception (Reimann et al 2010).
1.Primary Outcome
Title Change From Baseline to Week 4 in the Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Scores Using a Mixed Model for Repeated Measures
Hide Description The primary efficacy endpoint was the change from baseline to week 4 in the weekly average of the daily average NRS scores. The NRS is a widely-used, standard one-dimensional 11-point scale from 0=no pain to 10=worst pain imaginable as reported by patients. The daily average NRS scores is the average of the 2 NRS scores (recorded in the morning and evening) of average pain, defined as the patient-reported average pain intensity over the prior 12 hours. At least 1 of the 2 daily scores had to be recorded (non-missing) or the daily average was considered missing. Negative change from baseline values indicate a lessening of pain. The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the daily average NRS scores at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of the daily average NRS scores as covariate; and patient as a random effect.
Time Frame Baseline (day -7 to day -1), Week 4 (day 22 to day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; patients from one site are excluded due to lack of data integrity.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 100 98 100
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 98 participants 98 participants 100 participants
5.37  (0.992) 5.60  (1.236) 5.51  (0.963)
Change from baseline at week 4 Number Analyzed 94 participants 93 participants 97 participants
-1.64  (1.360) -1.71  (1.500) -1.90  (1.670)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the daily average NRS scores at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of the daily average NRS scores as covariate; and patient as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.130
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
-0.094 to 0.726
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the daily average NRS scores at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of the daily average NRS scores as covariate; and patient as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.245
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
-0.167 to 0.652
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 4 in the Weekly Average of the Average Numeric Rating Scale (NRS) Pain Scores Recorded in the Evening Using a Mixed Model for Repeated Measures
Hide Description The NRS is a widely-used, standard one-dimensional 11-point scale from 0=no pain to 10=worst pain imaginable as reported by patients. The NRS pain scores recorded in the evening is defined as the patient-reported average pain intensity over the prior 12 hours. Negative change from baseline values indicate a lessening of pain. The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the evening NRS scores at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of the evening NRS scores as covariate; and patient as a random effect.
Time Frame Baseline (day -7 to day -1), Week 4 (day 22 to day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants from one site are excluded due to lack of data integrity.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 100 98 100
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 98 participants 98 participants 100 participants
5.45  (1.073) 5.66  (1.320) 5.58  (0.994)
Change from baseline at week 4 Number Analyzed 94 participants 93 participants 97 participants
-1.70  (1.412) -1.73  (1.506) -1.96  (1.745)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the average NRS pain scores recorded in the evening at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of the average NRS pain scores recorded in the evening as covariate; and patient as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.128
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
-0.093 to 0.735
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the average NRS pain scores recorded in the evening at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of the average NRS pain scores recorded in the evening as covariate; and patient as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.194
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.27
Confidence Interval (2-Sided) 95%
-0.140 to 0.688
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to Week 4 in the Weekly Average of the Average Numeric Rating Scale (NRS) Pain Scores Recorded in the Morning Using a Mixed Model for Repeated Measures
Hide Description The NRS is a widely-used, standard one-dimensional 11-point scale from 0=no pain to 10=worst pain imaginable as reported by patients. The NRS pain scores recorded in the morning is defined as the patient-reported average pain intensity over the prior 12 hours. Negative change from baseline values indicate a lessening of pain. The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the evening NRS scores at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of morning NRS scores as covariate; and patient as a random effect.
Time Frame Baseline (day -7 to day -1), Week 4 (day 22 to day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants from one site are excluded due to lack of data integrity.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 100 98 100
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 98 participants 98 participants 100 participants
5.30  (0.980) 5.53  (1.226) 5.44  (0.968)
Change from baseline at week 4 Number Analyzed 94 participants 93 participants 97 participants
-1.60  (1.386) -1.68  (1.548) -1.84  (1.623)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the average NRS pain scores recorded in the morning at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of the average NRS pain scores recorded in the morning as covariate; and patient as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.177
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
-0.128 to 0.691
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the average NRS pain scores recorded in the morning at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of the average NRS pain scores recorded in the morning as covariate; and patient as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.325
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
-0.204 to 0.614
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to Week 4 in the Weekly Average of the Worst Numeric Rating Scale (NRS) Pain Scores Recorded in the Evening Using a Mixed Model for Repeated Measures
Hide Description The NRS is a widely-used, standard one-dimensional 11-point scale from 0=no pain to 10=worst pain imaginable as reported by patients. The worst pain is defined as the patient-reported worst pain intensity over the prior 24 hours. Negative change from baseline values indicate a lessening of pain. The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the worst pain NRS scores at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of the evening NRS scores as covariate; and patient as a random effect.
Time Frame Baseline (day -7 to day -1), Week 4 (day 22 to day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants from one site are excluded due to lack of data integrity.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 100 98 100
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 98 participants 98 participants 100 participants
6.09  (1.060) 6.35  (1.378) 6.09  (1.041)
Change from baseline at week 4 Number Analyzed 94 participants 93 participants 97 participants
-1.73  (1.576) -1.83  (1.657) -1.97  (1.883)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the worst NRS pain scores recorded in the evening at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of the worst NRS pain scores recorded in the evening as covariate; and patient as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.202
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
-0.158 to 0.741
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the worst NRS pain scores recorded in the evening at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of the worst NRS pain scores recorded in the evening as covariate; and patient as a random effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.457
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.457
Confidence Interval (2-Sided) 95%
-0.280 to 0.621
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With >=30% and >=50% Improvement From Baseline in the Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Scores at Week 4 Using a Mixed Model for Repeated Measures
Hide Description The NRS is a 11-point scale from 0=no pain to 10=worst pain imaginable as reported by patients. The daily average NRS scores is the average of the 2 NRS scores (recorded in the morning and evening) of average pain, defined as the patient-reported average pain intensity over the prior 12 hours. Percent improvement is calculated as 100 × (the weekly average of the daily average NRS pain score at week 4 – weekly average of the daily average NRS pain scores at baseline /weekly average of the daily average NRS pain scores at baseline. Patients missing a week 4 average are considered non-responders (<50% improvement or <30% improvement). The Mixed Model Repeated Measures (MMRM) model with change from baseline in the weekly average of the daily average NRS scores at week 4 as the dependent variable; week, pooled study center, treatment, and treatment by visit interaction as fixed factors, baseline weekly average of the daily average NRS scores as covariate; and patient as a random effect.
Time Frame Baseline (day -7 to day -1), Week 4 (day 22 to day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants from one site are excluded due to lack of data integrity.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 98 98 100
Measure Type: Number
Unit of Measure: percentage of participants
>=30% improvement from baseline 43.9 43.9 47.0
>=50% improvement from baseline 22.4 25.5 28.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments >=30% improvement. P-value, odds ratio and CI for odds ratio are calculated using logistic model including response (yes/no) as dependent variable, treatment group and pooled study sites as factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.815
Comments 5% level of significance
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.456 to 1.856
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments >=30% improvement. P-value, odds ratio and CI for odds ratio are calculated using logistic model including response (yes/no) as dependent variable, treatment group and pooled study sites as factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.893
Comments 5% level of significance
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.520 to 2.117
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments >=50% improvement. P-value, odds ratio and CI for odds ratio are calculated using logistic model including response (yes/no) as dependent variable, treatment group and pooled study sites as factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.430
Comments 5% level of significance
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.357 to 1.550
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments >=50% improvement. P-value, odds ratio and CI for odds ratio are calculated using logistic model including response (yes/no) as dependent variable, treatment group and pooled study sites as factors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.967
Comments 5% level of significance
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.494 to 2.088
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline to Weeks 2 and 4 in the Neuropathic Pain Symptom Inventory (NPSI) Total Score Using a Mixed Model for Repeated Measures (MMRM)
Hide Description

NPSI is a patient-reported questionnaire to evaluate the severity of different symptoms of neuropathic pain. The questionnaire contains 10 descriptors representing 5 distinct dimensions of pain: burning pain, deep pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia, plus 2 temporal items. Descriptors are scored from 0 through 10, where higher scores represent worse pain. The total score is the sum of the scores of the 10 descriptors (Bouhassira et al 2004). The total score ranges from 0 (no pain) through 100 (worst pain imaginable). If the score for one question was missing the total score was computed as 10 times sum of scores of 9 descriptors divided by 9. If more than one question was missing then the total score was missing. Negative change from baseline scores indicated less pain.

The MMRM used pooled study center, week, treatment, and treatment by week interaction as fixed factors and patient as a random factor.

Time Frame Baseline (day 1 prior to dosing), Weeks 2 (day 15) and Week 4 (day 29)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants from one site are excluded due to lack of data integrity.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 100 98 100
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 98 participants 98 participants 100 participants
41.9  (16.45) 44.0  (16.50) 44.0  (15.18)
Change from baseline at week 2 Number Analyzed 96 participants 92 participants 97 participants
-8.1  (14.13) -9.9  (15.65) -10.8  (14.68)
Change from baseline at week 4 Number Analyzed 90 participants 92 participants 97 participants
-13.1  (15.76) -14.3  (15.47) -16.8  (17.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments Change from baseline at Week 2 The MMRM used pooled study center, week, treatment, and treatment by week interaction as fixed factors and patient as a random factor. The unstructured covariance matrix for repeated observations within patients was used.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.251
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM of difference with placebo
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
-1.55 to 5.92
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments Change from baseline at Week 2. The MMRM used pooled study center, week, treatment, and treatment by week interaction as fixed factors and patient as a random factor. The unstructured covariance matrix for repeated observations within patients was used.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.495
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-2.46 to 5.07
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments Change from baseline at Week 4. The MMRM used pooled study center, week, treatment, and treatment by week interaction as fixed factors and patient as a random factor. The unstructured covariance matrix for repeated observations within patients was used.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.123
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 3.1
Confidence Interval (2-Sided) 95%
-0.84 to 7.06
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments Change from baseline at Week 4. The MMRM used pooled study center, week, treatment, and treatment by week interaction as fixed factors and patient as a random factor. The unstructured covariance matrix for repeated observations within patients was used.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.160
Comments 5% level of significance.
Method miex model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-1.12 to 6.77
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline to Week 4 in the Neuropathic Pain Impact on Quality of Life (NePIQoL) Total Score
Hide Description NePIQoL is a questionnaire that contains 41 items to evaluate quality of life in patients with neuropathic pain. Each question has responses ranging from strongly agree or always to strongly disagree or never. Questions are scored on a 5-point scale from 1 through 5, where higher scores represent greater pain-related interference in quality of life. Total range is 41 (great quality of life) to 205 (worst quality of life). Negative change from baseline scores indicated an improving quality of life.
Time Frame Baseline (day 1), Week 4 (day 29)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants from one site are excluded due to lack of data integrity.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 100 98 100
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 98 participants 98 participants 100 participants
127.1  (18.73) 126.5  (20.36) 127.6  (19.03)
Change from baseline at week 4 Number Analyzed 90 participants 92 participants 97 participants
-11.5  (17.98) 11.3  (20.09) -12.6  (19.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.609
Comments 5% level of significance
Method ANCOVA
Comments ANCOVA model includes study center, treatment, and baseline.
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-3.81 to 6.48
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.427
Comments 5% level of significance
Method ANCOVA
Comments ANCOVA model includes study center, treatment, and baseline.
Method of Estimation Estimation Parameter LSM difference with placebo
Estimated Value 2.1
Confidence Interval (2-Sided) 95%
-3.05 to 7.19
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Participants' Global Assess of Treatment as Measured by the Patient Global Impression of Change (PGIC) at Weeks 2 and 4 Using a Mixed Model for Repeated Measures (MMRM)
Hide Description

PGIC is a standardized self-report tool that measures the change in a patient's overall status rating since the start of treatment on 7-point scale (Hurst and Bolton 2004). The 7-point scale is defined as: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse.

The MMRM used pooled study center, week, treatment, and treatment by week interaction as fixed factors and patient as a random factor.

Time Frame Weeks 2 (day 15) and Week 4 (day 29)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants from one site are excluded due to lack of data integrity. Data collected beyond last dose of study medication plus 3 days are excluded from the analysis.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 100 98 100
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 2 Number Analyzed 96 participants 92 participants 97 participants
2.9  (0.87) 2.9  (0.92) 2.7  (0.82)
Week 4 Number Analyzed 90 participants 92 participants 97 participants
2.6  (1.08) 2.5  (1.12) 2.4  (1.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments Week 2 Mixed model for repeated measures (MMRM) with pooled study center, week, treatment, and treatment by week interaction as fixed factors and patient as a random factor. The unstructured covariance matrix for repeated observations within patients was used.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.166
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.07 to 0.43
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments Week 2 Mixed model for repeated measures (MMRM) with pooled study center, week, treatment, and treatment by week interaction as fixed factors and patient as a random factor. The unstructured covariance matrix for repeated observations within patients was used.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
0.00 to 0.51
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments Week 4 Mixed model for repeated measures (MMRM) with pooled study center, week, treatment, and treatment by week interaction as fixed factors and patient as a random factor. The unstructured covariance matrix for repeated observations within patients was used.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.152
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.08 to 0.53
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments Week 4 Mixed model for repeated measures (MMRM) with pooled study center, week, treatment, and treatment by week interaction as fixed factors and patient as a random factor. The unstructured covariance matrix for repeated observations within patients was used.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.342
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.16 to 0.46
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline to Weeks 2 and 4 in the Daily Sleep Interference Scale (DSIS) Using a Mixed Model for Repeated Measures
Hide Description

DSIS is an 11-point scale that asks the patient to “select the number that best describes how much your pain has interfered with your sleep during the past 24 hours.” Response options range from 0 (Did not interfere with sleep) to 10 (Completely interfered with sleep/unable to sleep due to pain). Negative change from baseline scores indicate improvement (lessening) of how much pain interfered with sleep.

The MMRM used pooled study center, week, treatment, and treatment by week interaction as fixed factors and patient as a random factor.

Time Frame Baseline (day 1 prior to dosing), Weeks 2 (day 15) and Week 4 (day 29)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants from one site are excluded due to lack of data integrity. Data collected beyond last dose of study medication plus 3 days are excluded from the analysis.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 100 98 100
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 98 participants 98 participants 100 participants
4.5  (1.94) 4.4  (2.26) 4.4  (2.00)
Change from baseline at week 2 Number Analyzed 96 participants 92 participants 97 participants
-1.1  (1.54) -1.1  (1.99) -1.3  (1.99)
Change from baseline at week 4 Number Analyzed 90 participants 92 participants 97 participants
-1.4  (1.78) -1.5  (2.16) -1.7  (2.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments Change from baseline at Week 2 The inferential model includes study center, week, treatment, and treatment by week interaction as the fixed factors; baseline as a covariate and unstructured variance-covariance structure in the initial model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.311
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.22 to 0.70
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments Change from baseline at week 2 The inferential model includes study center, week, treatment, and treatment by week interaction as the fixed factors; baseline as a covariate and unstructured variance-covariance structure in the initial model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.262
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.20 to 0.73
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments Change from baseline at week 4 The inferential model includes study center, week, treatment, and treatment by week interaction as the fixed factors; baseline as a covariate and unstructured variance-covariance structure in the initial model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.065
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-0.03 to 0.97
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments Change from baseline at week 4 The inferential model includes study center, week, treatment, and treatment by week interaction as the fixed factors; baseline as a covariate and unstructured variance-covariance structure in the initial model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.296
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.23 to 0.76
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Kaplan-Meier Estimates for First Time to Reach 30% or More Sustained Improvement in Weekly Average of the Daily Average NRS Pain Scores
Hide Description Percent improvement is calculated as 100*(the weekly average of the daily average NRS pain score – weekly average of the daily average NRS pain scores at baseline [days -7 to -1])/weekly average of the daily average NRS pain scores at baseline. Patients who do not reach >= 30% improvement are censored at their last non-missing weekly average. Patients who reach >= 30% improvement, but the improvement is not sustained through the end of the treatment period are censored at their last non-missing weekly average. For patients who reach >= 30% improvement that is sustained through the end through the end of the of the treatment, the time >= 30% improvement is first reached is used.
Time Frame Baseline (days -7 to -1), Week 1 (days 1-7), Week 2 (day 8-14), Week 3 (days 15-21), Week 4 (days 22-29)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants from one site are excluded due to lack of data integrity.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 98 98 100
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(15.000 to NA)
[1]
The median and 95% CI is not estimable if the proportion of participants’ with 30% improvement is less than 0.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.245
Comments 5% level of significance
Method Regression, Cox
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.304
Comments 5% level of significance
Method Regression, Cox
Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline to Weeks 2 and 4 in Maximal Intensity of Brush-Evoked Allodynia as Measured on an 11-point Numeric Rating Scale (NRS) Using a Mixed Model for Repeated Measures (MMRM)
Hide Description Allodynia refers to central pain sensitization (increased response of neurons) following normally non-painful, often repetitive, stimulation. In this case, pain evoked by innocuous brush is measured on an 11-point NRS where 0=no pain and 11=worst pain imaginable as reported by patients Negative change from baseline scores indicate improvement (lessening) of pain.
Time Frame Baseline (day 1 prior to dosing), Weeks 2 (day 15) and Week 4 (day 29)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants from one site are excluded due to lack of data integrity. Participants from two other sites are excluded dince the two sites incorrectly assessed allodynia. If brush-evoked allodynia was not present at screening, it was not rechecked on subsequent visits.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 100 98 100
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 79 participants 79 participants 85 participants
1.6  (1.54) 1.8  (2.28) 2.0  (2.24)
Change from baseline at week 2 Number Analyzed 54 participants 47 participants 62 participants
-0.7  (1.47) -1.0  (2.25) -0.8  (1.53)
Change from baseline at week 4 Number Analyzed 53 participants 46 participants 62 participants
-0.7  (1.45) -0.7  (2.30) -0.7  (1.76)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments Change from baseline at week 2 The inferential model includes study center, week, treatment, and treatment by week interaction as the fixed factors; baseline as a covariate and unstructured variance-covariance structure in the initial model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.556
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.61 to 0.33
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments Change from baseline at week 2 The inferential model includes study center, week, treatment, and treatment by week interaction as the fixed factors; baseline as a covariate and unstructured variance-covariance structure in the initial model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.482
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.65 to 0.31
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments Change from baseline at week 4. The inferential model includes study center, week, treatment, and treatment by week interaction as the fixed factors; baseline as a covariate and unstructured variance-covariance structure in the initial model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.333
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.81 to 0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments Change from baseline at week 4 The inferential model includes study center, week, treatment, and treatment by week interaction as the fixed factors; baseline as a covariate and unstructured variance-covariance structure in the initial model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.833
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.62 to 0.50
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline to Weeks 2 and 4 in Maximal Intensity of Punctate-Evoked Hyperalgesia as Measured on an 11-point Numeric Rating Scale (NRS) Using a Mixed Model for Repeated Measures (MMRM)
Hide Description

Hyperalgesia refers to increased pain from a stimulus that normally provokes pain. In this case, pain is evoked by punctate skin stimulation using a Medipin® and is measured on an 11-point NRS where 0=no pain and 11=worst pain imaginable as reported by patients. Negative change from baseline scores indicate improvement (lessening) of pain.

The MMRM used pooled study center, week, treatment, and treatment by week interaction as fixed factors and patient as a random factor. The unstructured covariance matrix for repeated observations within patients was used.

Time Frame Baseline (day 1 prior to dosing), Weeks 2 (day 15) and Week 4 (day 29)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants from one site are excluded due to lack of data integrity. Participants from two other sites are excluded since the two sites incorrectly assessed allodynia. If punctate-evoked hyperalgesia was not present at screening, it was not rechecked on subsequent visits.
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 100 98 100
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 79 participants 79 participants 85 participants
2.4  (2.03) 3.0  (2.48) 2.8  (2.57)
Change from baseline at week 2 Number Analyzed 60 participants 59 participants 64 participants
-1.0  (2.02) -1.3  (2.16) -1.1  (1.91)
Change from baseline at week 4 Number Analyzed 59 participants 57 participants 64 participants
-1.0  (2.08) -1.5  (2.36) -1.4  (2.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments Change from baseline at week 2 The inferential model includes study center, week, treatment, and treatment by week interaction as the fixed factors; baseline as a covariate and unstructured variance-covariance structure in the initial model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.563
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.75 to 0.41
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments Change from baseline at week 2. The inferential model includes study center, week, treatment, and treatment by week interaction as the fixed factors; baseline as a covariate and unstructured variance-covariance structure in the initial model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.804
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.64 to 0.50
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TV-45070 4%, Placebo
Comments Change from baseline at week 4 The inferential model includes study center, week, treatment, and treatment by week interaction as the fixed factors; baseline as a covariate and unstructured variance-covariance structure in the initial model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.714
Comments 5% level of significance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.49 to 0.71
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection TV-45070 8%, Placebo
Comments Change from baseline at week 4. The inferential model includes study center, week, treatment, and treatment by week interaction as the fixed factors; baseline as a covariate and unstructured variance-covariance structure in the initial model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.871
Comments 5% level of siignificance
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference from placebo
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.64 to 0.55
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Participants With Treatment-Emergent Adverse Events
Hide Description An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
Time Frame day 1 up to day 57
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title TV-45070 4% TV-45070 8% Placebo
Hide Arm/Group Description:
TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
Overall Number of Participants Analyzed 100 98 100
Measure Type: Count of Participants
Unit of Measure: Participants
Any treatment-emergent adverse event
15
  15.0%
32
  32.7%
24
  24.0%
Severe TEAE
0
   0.0%
1
   1.0%
0
   0.0%
Treatment-related TEAE
5
   5.0%
10
  10.2%
11
  11.0%
Deaths
0
   0.0%
0
   0.0%
0
   0.0%
Serious TEAE
0
   0.0%
1
   1.0%
0
   0.0%
Withdrawn from treatment due to TEAE
4
   4.0%
4
   4.1%
3
   3.0%
Time Frame day 1 up to day 57
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title TV-45070 4% TV-45070 (8%) Placebo
Hide Arm/Group Description TV-45070 ointment in a 4% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28. TV-45070 ointment in a 8% strength applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28. Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.
All-Cause Mortality
TV-45070 4% TV-45070 (8%) Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/100 (0.00%)      0/98 (0.00%)      0/100 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
TV-45070 4% TV-45070 (8%) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/100 (0.00%)      1/98 (1.02%)      0/100 (0.00%)    
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure  1  0/100 (0.00%)  0 1/98 (1.02%)  1 0/100 (0.00%)  0
1
Term from vocabulary, MedDRA (17.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TV-45070 4% TV-45070 (8%) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/100 (2.00%)      5/98 (5.10%)      1/100 (1.00%)    
General disorders       
Application site erythema  1  2/100 (2.00%)  3 5/98 (5.10%)  5 1/100 (1.00%)  2
1
Term from vocabulary, MedDRA (17.1)
Indicates events were collected by systematic assessment
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.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor’s review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor’s designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc
Phone: 1-888-483-8279
Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT02365636     History of Changes
Other Study ID Numbers: TV-45070-CNS-20013
First Submitted: February 13, 2015
First Posted: February 19, 2015
Results First Submitted: September 22, 2018
Results First Posted: October 23, 2018
Last Update Posted: October 23, 2018