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

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02365636
• Collaborator: (none)
• Enrollment: 300
• Locations: 77
• Arms: 3
• Actual Duration (Months): 26.4
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a study to evaluate the safety and efficacy of 4% and 8% w/w TV 45070 ointment compared with placebo ointment applied topically and twice daily to the area of PHN pain for 4 weeks in patients with PHN

Condition or Disease	Intervention/Treatment	Phase
Postherpetic Neuralgia	Drug: TV-45070; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Topically Applied TV-45070 (4% and 8% w/w Ointment) in Patients With Postherpetic Neuralgia.
• Actual Study Start Date: Feb 26, 2015
• Actual Primary Completion Date: May 9, 2017
• Actual Study Completion Date: May 9, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TV-45070 4% 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.	Drug: TV-45070; TV-45070 is an ointment applied topically twice daily to area of pain.; Other Names: funapide XEN402
Experimental: TV-45070 8% 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.	Drug: TV-45070; TV-45070 is an ointment applied topically twice daily to area of pain.; Other Names: funapide XEN402
Placebo Comparator: Placebo Placebo ointment applied topically twice daily to the area of postherpetic neuralgia (PHN) pain during the treatment period from days 1 through 28.	Drug: Placebo; The matching placebo ointment contained only the excipients of the active treatment; also applied topically twice daily to area of pain.

Outcome Measures

Primary Outcome Measures

1. 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 [Baseline (day -7 to day -1), Week 4 (day 22 to day 28)]

   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.

Secondary Outcome Measures

1. 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 [Baseline (day -7 to day -1), Week 4 (day 22 to day 28)]

   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.

2. 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 [Baseline (day -7 to day -1), Week 4 (day 22 to day 28)]

   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.

3. 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 [Baseline (day -7 to day -1), Week 4 (day 22 to day 28)]

   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.

4. 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 [Baseline (day -7 to day -1), Week 4 (day 22 to day 28)]

   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.

5. 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) [Baseline (day 1 prior to dosing), Weeks 2 (day 15) and Week 4 (day 29)]

   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.

6. Change From Baseline to Week 4 in the Neuropathic Pain Impact on Quality of Life (NePIQoL) Total Score [Baseline (day 1), Week 4 (day 29)]

   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.

7. 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) [Weeks 2 (day 15) and Week 4 (day 29)]

   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.

8. Change From Baseline to Weeks 2 and 4 in the Daily Sleep Interference Scale (DSIS) Using a Mixed Model for Repeated Measures [Baseline (day 1 prior to dosing), Weeks 2 (day 15) and Week 4 (day 29)]

   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.

9. Kaplan-Meier Estimates for First Time to Reach 30% or More Sustained Improvement in Weekly Average of the Daily Average NRS Pain Scores [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)]

   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.

10. 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) [Baseline (day 1 prior to dosing), Weeks 2 (day 15) and Week 4 (day 29)]

    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.

11. 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) [Baseline (day 1 prior to dosing), Weeks 2 (day 15) and Week 4 (day 29)]

    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.

12. Participants With Treatment-Emergent Adverse Events [day 1 up to day 57]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient has chronic Postherpetic Neuralgia (PHN), defined as pain present for more than 6 months and less than 10 years after onset of herpes zoster skin rash affecting a single dermatome. Patients with more than 1 involved dermatome may also be included, provided the affected dermatomes are contiguous.

• Patient is ≥18 years of age, with a body mass index (BMI) between 18 and 34 kg/m2, inclusive, at the screening visit.

• If the patient is a woman and is fertile, the patient is not pregnant and has negative pregnancy tests at both the screening and randomization visits, and agrees to use an acceptable method of contraception for the duration of the study, including follow-up.

• If the patient is a man and is capable of producing offspring, the patient must agree to use an acceptable method of contraception, unless the partner cannot become pregnant for the duration of the study, including follow-up.

• Patient must sign the written Informed Consent Form (ICF) for the study and be willing to comply with all study procedures and restrictions.

• Patient must be judged by the investigator to be medically healthy (except for PHN) and able to participate in the study

• Other criteria apply, please contact the investigator for more information

Exclusion Criteria:

• Patient has any other severe pain that might confound assessment or self-evaluation of pain due to PHN.

• Patient has PHN affecting the face (trigeminal nerve distribution).

• Patient has a history, in the judgment of the investigator, of inadequate response to more than 3 adequate courses of treatment with other medications used to treat neuropathic pain (eg, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, anticonvulsants, topical lidocaine, and/or topical capsaicin).

• Patient is taking oral analgesics (either opioid or non-opioid) or is receiving topical therapy such as the 5% topical lidocaine patch for the treatment of pain and is unwilling or unable to complete a washout period during which the patient will discontinue analgesic therapy or topical pain therapy.

• Patient has been treated with topical capsaicin at any time in the past 6 months for neuropathic pain.

• Patient has a history of fibromyalgia.

• Other criteria apply, please contact the investigator for more information

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 13052	Birmingham	Alabama	United States	35213
2	Teva Investigational Site 13086	Mobile	Alabama	United States	36608
3	Teva Investigational Site 13514	Phoenix	Arizona	United States	85018
4	Teva Investigational Site 13520	Phoenix	Arizona	United States	85023
5	Teva Investigational Site 13661	Little Rock	Arkansas	United States	72205
6	Teva Investigational Site 13079	Colton	California	United States	92324
7	Teva Investigational Site 13331	Pomona	California	United States	91767
8	Teva Investigational Site 13341	Sacramento	California	United States	95821
9	Teva Investigational Site 13051	Santa Monica	California	United States	90404
10	Teva Investigational Site 13055	Thousand Oaks	California	United States	91360
11	Teva Investigational Site 13100	Torrance	California	United States	90505
12	Teva Investigational Site 13657	Milford	Connecticut	United States	06460
13	Teva Investigational Site 13521	Brandon	Florida	United States	33511
14	Teva Investigational Site 13085	Brooksville	Florida	United States	34601
15	Teva Investigational Site 13057	Clearwater	Florida	United States	33761
16	Teva Investigational Site 13084	Fort Myers	Florida	United States	33912
17	Teva Investigational Site 13047	Hialeah	Florida	United States	33012
18	Teva Investigational Site 13046	Homestead	Florida	United States	33030
19	Teva Investigational Site 13098	Jacksonville	Florida	United States	32256
20	Teva Investigational Site 13045	Kissimmee	Florida	United States	34744
21	Teva Investigational Site 13064	Miami	Florida	United States	33126
22	Teva Investigational Site 13338	Miami	Florida	United States	33135
23	Teva Investigational Site 13044	Miami	Florida	United States	33176
24	Teva Investigational Site 13335	Miami	Florida	United States	33183
25	Teva Investigational Site 13522	Naples	Florida	United States	34102
26	Teva Investigational Site 13058	New Port Richey	Florida	United States	34652
27	Teva Investigational Site 13076	Oldsmar	Florida	United States	34677
28	Teva Investigational Site 13073	Orlando	Florida	United States	32801
29	Teva Investigational Site 13048	Orlando	Florida	United States	32806
30	Teva Investigational Site 13659	Pembroke Pines	Florida	United States	33024
31	Teva Investigational Site 13056	Saint Petersburg	Florida	United States	33713
32	Teva Investigational Site 13519	Seminole	Florida	United States	33708
33	Teva Investigational Site 13059	Tampa	Florida	United States	33603
34	Teva Investigational Site 13329	Venice	Florida	United States	34292
35	Teva Investigational Site 13513	Virginia Gardens	Florida	United States	33172
36	Teva Investigational Site 13053	Atlanta	Georgia	United States	30331
37	Teva Investigational Site 13063	Marietta	Georgia	United States	30060
38	Teva Investigational Site 13091	Aurora	Illinois	United States	60506
39	Teva Investigational Site 13072	Bolingbrook	Illinois	United States	60490
40	Teva Investigational Site 13062	Evansville	Indiana	United States	47714
41	Teva Investigational Site 13093	Evansville	Indiana	United States	47725
42	Teva Investigational Site 13074	Monroe	Louisiana	United States	71201
43	Teva Investigational Site 13660	Shreveport	Louisiana	United States	71105
44	Teva Investigational Site 13094	Brockton	Massachusetts	United States	02301
45	Teva Investigational Site 13061	Detroit	Michigan	United States	48235
46	Teva Investigational Site 13049	Farmington Hills	Michigan	United States	48334
47	Teva Investigational Site 13099	Saint Louis	Missouri	United States	63141
48	Teva Investigational Site 13065	Las Vegas	Nevada	United States	89123
49	Teva Investigational Site 13066	Albuquerque	New Mexico	United States	87102
50	Teva Investigational Site 13330	Albuquerque	New Mexico	United States	87108-5129
51	Teva Investigational Site 13658	Albany	New York	United States	12208
52	Teva Investigational Site 13334	Brooklyn	New York	United States	11229
53	Teva Investigational Site 13054	New York	New York	United States	10128
54	Teva Investigational Site 13083	North Massapequa	New York	United States	11758-1802
55	Teva Investigational Site 13060	Calabash	North Carolina	United States	28467
56	Teva Investigational Site 13337	Raleigh	North Carolina	United States	27612
57	Teva Investigational Site 13082	Winston-Salem	North Carolina	United States	27103
58	Teva Investigational Site 13089	Columbus	Ohio	United States	43214
59	Teva Investigational Site 13075	Oklahoma City	Oklahoma	United States	73103
60	Teva Investigational Site 13328	Oklahoma City	Oklahoma	United States	73104
61	Teva Investigational Site 13516	Oklahoma City	Oklahoma	United States	73112
62	Teva Investigational Site 13078	Eugene	Oregon	United States	97404
63	Teva Investigational Site 13333	Levittown	Pennsylvania	United States	19056
64	Teva Investigational Site 13339	Philadelphia	Pennsylvania	United States	19146
65	Teva Investigational Site 13327	Pittsburgh	Pennsylvania	United States	15206
66	Teva Investigational Site 13332	Charleston	South Carolina	United States	29406
67	Teva Investigational Site 13068	Rapid City	South Dakota	United States	57702
68	Teva Investigational Site 13095	Knoxville	Tennessee	United States	37909
69	Teva Investigational Site 13096	Memphis	Tennessee	United States	38119
70	Teva Investigational Site 13070	Arlington	Texas	United States	76012
71	Teva Investigational Site 13088	Austin	Texas	United States	78731
72	Teva Investigational Site 13340	McKinney	Texas	United States	75071
73	Teva Investigational Site 13050	Plano	Texas	United States	75093
74	Teva Investigational Site 13518	Salt Lake City	Utah	United States	84124
75	Teva Investigational Site 13090	Norfolk	Virginia	United States	23507
76	Teva Investigational Site 13081	Bellevue	Washington	United States	98007
77	Teva Investigational Site 13336	Seattle	Washington	United States	98195

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

• Study Protocol - Apr 21, 2016
• Statistical Analysis Plan - Sep 8, 2015

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT02365636
• Other Study ID Numbers: TV-45070-CNS-20013
• First Posted: Feb 19, 2015
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neuralgia; Neuralgia, Postherpetic

Study Results

Participant Flow

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 Detail	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
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	100
Full Analysis Set	100	98	100
COMPLETED	94	93	97
NOT COMPLETED	6	7	3

Baseline Characteristics

Arm/Group Title	TV-45070 4%	TV-45070 8%	Placebo	Total
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 Participants	100	100	100	300
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.2 (15.99)	57.6 (16.61)	58.6 (15.80)	57.8 (16.09)
Sex: Female, Male (Count of Participants)
Female	57 57%	50 50%	65 65%	172 57.3%
Male	43 43%	50 50%	35 35%	128 42.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	56 56%	53 53%	70 70%	179 59.7%
Not Hispanic or Latino	43 43%	47 47%	30 30%	120 40%
Unknown or Not Reported	1 1%	0 0%	0 0%	1 0.3%
Race/Ethnicity, Customized (Count of Participants)
White	81 81%	79 79%	90 90%	250 83.3%
Black or African American	13 13%	17 17%	7 7%	37 12.3%
Asian	3 3%	3 3%	1 1%	7 2.3%
American Indian or Alaskan Native	1 1%	1 1%	1 1%	3 1%
Other	2 2%	0 0%	1 1%	3 1%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	77.02 (13.775)	77.41 (13.383)	77.86 (15.111)	77.43 (14.066)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	167.27 (10.258)	168.03 (8.203)	165.82 (10.355)	167.04 (9.668)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.42 (3.457)	27.30 (3.452)	28.15 (3.798)	27.62 (3.580)
R1150W Polymorphism Status (Count of Participants)
Homozygous minor allele (positive, AA)	1 1%	2 2%	0 0%	3 1%
Heterozygous (positive, AG)	17 17%	25 25%	22 22%	64 21.3%
Homozygous common allele (negative, GG)	82 82%	73 73%	78 78%	233 77.7%

Outcome Measures

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
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)

Outcome Measure Data

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
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.
Measure Participants	100	98	100
Baseline	5.37 (0.992)	5.60 (1.236)	5.51 (0.963)
Change from baseline at week 4	-1.64 (1.360)	-1.71 (1.500)	-1.90 (1.670)

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
Statistical Test of Hypothesis	p-Value	0.130
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 95%; -0.094 to 0.726
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.245
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 95%; -0.167 to 0.652
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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)

Outcome Measure Data

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
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.
Measure Participants	100	98	100
Baseline	5.45 (1.073)	5.66 (1.320)	5.58 (0.994)
Change from baseline at week 4	-1.70 (1.412)	-1.73 (1.506)	-1.96 (1.745)

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
Statistical Test of Hypothesis	p-Value	0.128
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 95%; -0.093 to 0.735
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.194
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.27
	Confidence Interval	(2-Sided) 95%; -0.140 to 0.688
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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)

Outcome Measure Data

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
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.
Measure Participants	100	98	100
Baseline	5.30 (0.980)	5.53 (1.226)	5.44 (0.968)
Change from baseline at week 4	-1.60 (1.386)	-1.68 (1.548)	-1.84 (1.623)

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
Statistical Test of Hypothesis	p-Value	0.177
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95%; -0.128 to 0.691
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.325
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95%; -0.204 to 0.614
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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)

Outcome Measure Data

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
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.
Measure Participants	100	98	100
Baseline	6.09 (1.060)	6.35 (1.378)	6.09 (1.041)
Change from baseline at week 4	-1.73 (1.576)	-1.83 (1.657)	-1.97 (1.883)

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
Statistical Test of Hypothesis	p-Value	0.202
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.29
	Confidence Interval	(2-Sided) 95%; -0.158 to 0.741
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.457
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.457
	Confidence Interval	(2-Sided) 95%; -0.280 to 0.621
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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)

Outcome Measure Data

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
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.
Measure Participants	98	98	100
>=30% improvement from baseline	43.9 43.9%	43.9 43.9%	47.0 47%
>=50% improvement from baseline	22.4 22.4%	25.5 25.5%	28.0 28%

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
Statistical Test of Hypothesis	p-Value	0.815
	Comments	5% level of significance
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.456 to 1.856
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.893
	Comments	5% level of significance
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.520 to 2.117
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.430
	Comments	5% level of significance
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.357 to 1.550
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.967
	Comments	5% level of significance
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.494 to 2.088
	Parameter Dispersion	Type: Value:
	Estimation Comments

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)
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)

Outcome Measure Data

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
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.
Measure Participants	100	98	100
Baseline	41.9 (16.45)	44.0 (16.50)	44.0 (15.18)
Change from baseline at week 2	-8.1 (14.13)	-9.9 (15.65)	-10.8 (14.68)
Change from baseline at week 4	-13.1 (15.76)	-14.3 (15.47)	-16.8 (17.78)

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
Statistical Test of Hypothesis	p-Value	0.251
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM of difference with placebo
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95%; -1.55 to 5.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.495
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -2.46 to 5.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.123
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	3.1
	Confidence Interval	(2-Sided) 95%; -0.84 to 7.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.160
	Comments	5% level of significance.
	Method	miex model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	2.8
	Confidence Interval	(2-Sided) 95%; -1.12 to 6.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline to Week 4 in the Neuropathic Pain Impact on Quality of Life (NePIQoL) Total Score
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)

Outcome Measure Data

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
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.
Measure Participants	100	98	100
Baseline	127.1 (18.73)	126.5 (20.36)	127.6 (19.03)
Change from baseline at week 4	-11.5 (17.98)	11.3 (20.09)	-12.6 (19.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TV-45070 4%, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
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
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TV-45070 8%, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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)
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)

Outcome Measure Data

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
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.
Measure Participants	100	98	100
Week 2	2.9 (0.87)	2.9 (0.92)	2.7 (0.82)
Week 4	2.6 (1.08)	2.5 (1.12)	2.4 (1.07)

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
Statistical Test of Hypothesis	p-Value	0.166
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.07 to 0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.046
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; 0.00 to 0.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.152
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.342
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.16 to 0.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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)

Outcome Measure Data

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
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.
Measure Participants	100	98	100
Baseline	4.5 (1.94)	4.4 (2.26)	4.4 (2.00)
Change from baseline at week 2	-1.1 (1.54)	-1.1 (1.99)	-1.3 (1.99)
Change from baseline at week 4	-1.4 (1.78)	-1.5 (2.16)	-1.7 (2.24)

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
Statistical Test of Hypothesis	p-Value	0.311
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.22 to 0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.262
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.065
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.296
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.23 to 0.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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)

Outcome Measure Data

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
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.
Measure Participants	98	98	100
Median (95% Confidence Interval) [days]	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TV-45070 4%, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.245
	Comments	5% level of significance
	Method	Regression, Cox
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TV-45070 8%, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.304
	Comments	5% level of significance
	Method	Regression, Cox
	Comments

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)
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)

Outcome Measure Data

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
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.
Measure Participants	100	98	100
Baseline	1.6 (1.54)	1.8 (2.28)	2.0 (2.24)
Change from baseline at week 2	-0.7 (1.47)	-1.0 (2.25)	-0.8 (1.53)
Change from baseline at week 4	-0.7 (1.45)	-0.7 (2.30)	-0.7 (1.76)

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
Statistical Test of Hypothesis	p-Value	0.556
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.61 to 0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.482
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.65 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.333
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.81 to 0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.833
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.62 to 0.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

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)
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)

Outcome Measure Data

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
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.
Measure Participants	100	98	100
Baseline	2.4 (2.03)	3.0 (2.48)	2.8 (2.57)
Change from baseline at week 2	-1.0 (2.02)	-1.3 (2.16)	-1.1 (1.91)
Change from baseline at week 4	-1.0 (2.08)	-1.5 (2.36)	-1.4 (2.00)

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
Statistical Test of Hypothesis	p-Value	0.563
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.75 to 0.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.804
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.64 to 0.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.714
	Comments	5% level of significance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.49 to 0.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.871
	Comments	5% level of siignificance
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference from placebo
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.64 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Participants With Treatment-Emergent Adverse Events
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

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	TV-45070 4%	TV-45070 8%	Placebo
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.
Measure Participants	100	98	100
Any treatment-emergent adverse event	15 15%	32 32%	24 24%
Severe TEAE	0 0%	1 1%	0 0%
Treatment-related TEAE	5 5%	10 10%	11 11%
Deaths	0 0%	0 0%	0 0%
Serious TEAE	0 0%	1 1%	0 0%
Withdrawn from treatment due to TEAE	4 4%	4 4%	3 3%

Adverse Events

Time Frame	day 1 up to day 57
Arm/Group Title	TV-45070 4%		TV-45070 (8%)		Placebo
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		0/98 (0%)		0/100 (0%)
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%)		1/98 (1%)		0/100 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/100 (0%)	0	1/98 (1%)	1	0/100 (0%)	0
Other (Not Including Serious) Adverse Events
	TV-45070 4%		TV-45070 (8%)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/100 (2%)		5/98 (5.1%)		1/100 (1%)
General disorders
Application site erythema	2/100 (2%)	3	5/98 (5.1%)	5	1/100 (1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.