STEP: A Study to Evaluate Efficacy and Safety of a Single Application of Capsaicin 8%Transdermal Delivery System Compared to Placebo in Reducing Pain Intensity in Subjects With Painful Diabetic Peripheral Neuropathy (PDPN)
Sponsor
Astellas Pharma Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT01533428
Collaborator
(none)
369
29
2
24
12.7
0.5
Study Details
Study Description
Brief Summary
The purpose of the study is to assess efficacy and safety of a single treatment of Capsaicin 8% transdermal delivery system in reducing pain from damaged nerves (neuropathic pain) caused by diabetes.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Participants were divided into 2 groups of approximately equal size. In the first group, participants received a Capsaicin 8% patch applied for 30 minutes to the feet; in the second group, participants received a placebo patch applied for 30 minutes to the feet. Participants were involved in the study for approximately 12 weeks and have visited the clinic approximately 6 times.
Study Design
Study Type:
Interventional
Actual Enrollment
:
369 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase III, Double-blind, Randomized, Placebo-controlled, Multicenter Study Evaluating the Efficacy and Safety of QUTENZA® in Subjects With Painful Diabetic Peripheral Neuropathy
Study Start Date
:
Feb 1, 2012
Actual Primary Completion Date
:
Feb 1, 2014
Actual Study Completion Date
:
Feb 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Capsaicin 8% Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 |
Drug: Capsaicin 8%
Capsaicin 8% transdermal delivery system
Other Names:
|
| Placebo Comparator: Placebo Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
Drug: Placebo
Placebo Patch
|
Outcome Measures
Primary Outcome Measures
- Percent Change in the Average Daily Pain Score From Baseline to Between Weeks 2 and 8 [Baseline to between Weeks 2 to 8]
Percent change in the average daily pain score from baseline to between Weeks 2 and 8, measured using Question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN). Participants assessed their pain due to diabetes in the last 24 hours on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine).
Secondary Outcome Measures
- Percent Change in the Average Daily Pain Score From Baseline to Between Weeks 2 and 12 [Baseline to between Weeks 2 and 12]
Percent Change in the Average Daily Pain Score from baseline to between Weeks 2 and 12 measured using Question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN). Participants assessed their pain due to diabetes in the last 24 hours on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine).
- Weekly Percent Change From Baseline in Average Daily Pain Score [Baseline to Weeks 2, 3, 4, 5, 6, 7, 8, 9,10, 11 and 12]
Weekly Percent Change from baseline in average daily pain score from baseline to Week 12 measured using Question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN). Participants assessed their pain due to diabetes in the last 24 hours on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine).
- Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline [Baseline and Weeks 2, 4, 8 and 12]
Weekly average of average daily pain score at Baseline and Weeks 2,4,8 and 12 measured using Question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN). Participants assessed their pain due to diabetes in the last 24 hours on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine).
- Percentage of Participants With 30% Reduction in Average Daily Pain Score. [Baseline, Weeks 2-8 and Weeks 2-12]
Percentage of participants achieving 30% decrease in the average daily pain score in Weeks 2 and 8 and Weeks 2 and 12 measured using Question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN). Participants assessed their pain on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine).
- Percentage of Participants With 50% Reduction in Average Daily Pain Score. [Baseline, Weeks 2-8 and Weeks 2-12]
Percentage of participants achieving 50% decrease in the average daily pain score in Weeks 2 and 8 and Weeks 2 and 12 measured using Question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN). Participants assessed their pain on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine).
- Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 [Baseline to Week 2]
Overall participant status assessed using Patient Global Impression of Change (PGIC) self-assessment questionnaire which was used by participants to report on 7 categories listed as follows; Very Much Improved, Much Improved, Minimally Improved, No Change, Minimally Worse, Much Worse and Very Much Worse in Week 2
- Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 [Baseline to Week 8]
Overall participant status assessed using Patient Global Impression of Change (PGIC) self-assessment questionnaire which was used by participants to report on 7 categories listed as follows; Very Much Improved, Much Improved, Minimally Improved, No Change, Minimally Worse, Much Worse and Very Much Worse in Week 8
- Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 [Baseline to Week 12]
Overall participant status assessed using Patient Global Impression of Change (PGIC) self-assessment questionnaire which was used by participants to report on 7 categories listed as follows; Very Much Improved, Much Improved, Minimally Improved, No Change, Minimally Worse, Much Worse and Very Much Worse in Week 12
- Change From Baseline in the European Quality Of Life (QOL) Questionnaire in 5 Dimensions (EQ-5D) With Visual Analog Scale (VAS) to Weeks 2, 8 and 12 [Baseline to Weeks 2, 8 and 12]
Change from Baseline in the European Quality Of Life (QOL) questionnaire in 5 dimensions (EQ-5D) with Visual Analog Scale (VAS) to Weeks 2, 8 and 12. EQ-5D self-reported questionnaire is used to measure health-related quality of life by measuring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D questionnaire includes a visual analog scale (VAS) which records participants self-rated health status on a graduated (0-100) scale with higher scores indicating higher Health-Related Quality of Life (HRQoL).
- Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Scale From Baseline to Weeks 2, 8 and 12 [Baseline to Weeks 2, 8 and 12]
The Hospital Anxiety and Depression Scale (HADS) is a self-report scale developed for the assessment of anxiety and depression, that contain 14 items rated on a 4-point Likert-type scale. There are 2 subscales,one assessing depression and the other anxiety. The 7-item depression and anxiety subscales yield scores of 0 to 21 that are interpreted with the following cut-off points: 0 to 7, normal; 8 to 10, mild mood disturbance; 11 to 14, moderate mood disturbance; and 15 to 21, severe mood disturbance.
- Change in Hospital Anxiety and Depression Scale (HADS) Depression Scale From Baseline to Weeks 2, 8 and 12. [Baseline to Weeks 2, 8 and 12]
The Hospital Anxiety and Depression Scale (HADS) is a self-report scale developed for the assessment of anxiety and depression, it contains 14 items rated on a 4-point Likert-type scale. There are 2 subscales,one assessing depression and the other anxiety. The 7-item depression and anxiety subscales yield scores of 0 to 21 that are interpreted with the following cut-off points: 0 to 7, normal; 8 to 10, mild mood disturbance; 11 to 14, moderate mood disturbance; and 15 to 21, severe mood disturbance.
- Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 [Baseline, Weeks 8 and 12]
Treatment satisfaction assessment based on Self-Assessment Treatment (SAT II) questionnaire and the question "Over the past 7 days, how much has the study treatment improved your pain level?"
- Percent Change in Average Sleep Interference Score From Baseline to Between Weeks 2-8 and Weeks 2-12 [Baseline, Weeks 2-8 and Weeks 2-12]
Percent change in average sleep interference was measured by Question 9F of the Brief Pain Inventory-Diabetic Neuropathy (BPI DN) and was used to assess pain and sleep interference index. Daily sleep interference rating scale consists of an 11-point numerical scale with which the patient describes how pain related to diabetes has interfered with their sleep during the past 24 hours. On a scale 0 identifies "pain does not interfere with sleep" and 10 identifies "pain completely interferes with sleep". Average sleep interference score is assessed from baseline to Weeks 2-8 and Weeks 2-12.
- Tolerability of Patch Application Assessed by Dermal Assessment on Day 1, 15 Minutes and 60 Minutes After Patch Removal. [Day 1, 15 minutes and 60 minutes after patch removal]
Tolerability of patch application was assessed by dermal assessment (0 to 7 point severity score on Dermal Assessment Scale). Data reported is based on the number of participants in the combined category with a score ≥ 4 (Definite edema or higher), 15 and 60 minutes after patch removal.
- Change From Pre-application in"Pain Now" Score [Pre-application and 15 minutes and 60 minutes after patch removal]
Change from pre-application in"Pain Now" score was measured on a scale from 0-10 where 0 equates to "No Pain" and 10 to "Pain as bad as you can imagine". Participants were asked to provide pain ratings relative only to the area of pain undergoing treatment.
- Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 [Days 1 - 5]
Summarized number of participants who used Rescue Pain Medications for Pain
- Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 [Baseline to Week 12]
Number of patients assessed for Safety through Adverse Events (AE) and Serious Adverse Events (SAE), vital signs, and laboratory analyses from baseline to week 12
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of painful, distal, symmetrical, sensorimotor polyneuropathy which is due to diabetes, for at least 1 year prior to screening visit
-
Average Numeric Pain Rating Scale (NPRS) score over the last 24 hours of ≥4 at the screening and the baseline visit
Exclusion Criteria:
-
Primary pain associated with PDPN (Painful Diabetic Peripheral Neuropathy) in the ankles or above
-
Pain that could not be clearly differentiated from, or conditions that might interfere with the assessment of PDPN (Painful Diabetic Peripheral Neuropathy), neurological disorders unrelated to diabetic neuropathy (e.g., phantom limb pain from amputation); skin condition in the area of the neuropathy that could alter sensation (e.g., plantar ulcer)
-
Current or previous foot ulcer as determined by medical history and medical examination
-
Any amputation of lower extremity
-
Severe renal disease as defined by a creatinine clearance of <30 ml/min calculated according to the Cockcroft-Gault formula
-
Clinically significant cardiovascular disease within 6 months prior to screening visit defined as cerebrovascular accident, unstable or poorly controlled hypertension, transient ischemic attack, myocardial infarction, unstable angina, current arrhythmia, any heart surgery including coronary artery bypass graft surgery, percutaneous coronary angioplasty/stent placement, or valvular heart disease
-
Significant peripheral vascular disease (intermittent claudication or lack of pulsation of either the dorsalis pedis or posterior tibial artery, or ankle-brachial systolic blood pressure index of <0.80)
-
Clinically significant foot deformities, including hallux rigidus, hallux valgus, or rigid toe as determined by physical examination as judged by the investigator
-
Clinically significant ongoing, uncontrolled or untreated abnormalities in cardiac, renal, hepatic, or pulmonary function that may interfere either with the ability to complete the study or the evaluation of adverse events
-
Diagnosis of any poorly controlled major psychiatric disorder
-
Active substance abuse or history of chronic substance abuse within 1 year prior to screening visit or any prior chronic substance abuse (including alcoholism) likely to re-occur during the study period as judged by the investigator
-
Hypersensitivity to capsaicin (i.e., chili peppers or over-the-counter [OTC] capsaicin products), any Capsaicin 8% transdermal delivery system excipients, Eutectic Mixture of Local Anaesthetics (EMLA) ingredients or adhesives
-
Use of any topical pain medication, such as non-steroidal anti-inflammatory drugs, menthol, methyl salicylate, local anesthetics, steroids or capsaicin products on the painful areas within 7 days preceding the first patch application at the baseline visit
-
Use of oral or transdermal opioids exceeding a total daily dose of morphine of 80 mg/day, or equivalent; or any parenteral opioids, regardless of dose, within 7 days preceding the first patch application at the baseline visit
-
Skin areas to be treated with Capsaicin 8% transdermal delivery system showing changes such as crusting or ulcers
-
Planned elective surgery during the trial
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Site: 125 | Anniston | Alabama | United States | 36207 |
| 2 | Site: 131 | Fresno | California | United States | 93720 |
| 3 | Site: 123 | Long Beach | California | United States | 90806 |
| 4 | Site: 116 | Los Angeles | California | United States | 90033 |
| 5 | Site: 112 | Orange | California | United States | 92868 |
| 6 | Site: 130 | Walnut Creek | California | United States | 94597 |
| 7 | Site: 113 | Milford | Connecticut | United States | 06460 |
| 8 | Site: 119 | New London | Connecticut | United States | 06320 |
| 9 | Site: 117 | Boynton Beach | Florida | United States | 33435 |
| 10 | Site: 124 | Bradenton | Florida | United States | 34205 |
| 11 | Site: 107 | Clearwater | Florida | United States | 33765 |
| 12 | Site: 120 | Jupiter | Florida | United States | 33458 |
| 13 | Site: 108 | Orlando | Florida | United States | 32806 |
| 14 | Site: 132 | Oviedo | Florida | United States | 32765 |
| 15 | Site: 127 | St. Petersburg | Florida | United States | 33709 |
| 16 | Site: 122 | Tampa | Florida | United States | 33606 |
| 17 | Site: 133 | Honolulu | Hawaii | United States | 96814 |
| 18 | Site: 126 | New Bedford | Massachusetts | United States | 02740 |
| 19 | Site: 115 | Ann Arbor | Michigan | United States | 48104 |
| 20 | Site: 128 | Hazelwood | Missouri | United States | 63042 |
| 21 | Site:111 | New York | New York | United States | 10029 |
| 22 | Site: 110 | Winston-Salem | North Carolina | United States | 27103 |
| 23 | Site: 121 | Kettering | Ohio | United States | 45429 |
| 24 | Site:106 | Dallas | Texas | United States | 75230 |
| 25 | Site: 118 | Houston | Texas | United States | 77030 |
| 26 | Site: 114 | Houston | Texas | United States | 77098 |
| 27 | Site: 103 | Lubbock | Texas | United States | 79410 |
| 28 | Site: 105 | San Antonio | Texas | United States | 78228 |
| 29 | Site: 102 | San Antonio | Texas | United States | 78229 |
Sponsors and Collaborators
- Astellas Pharma Inc
Investigators
- Study Chair: Clinical Study Manager, Astellas Pharma Europe B.V.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01533428
Other Study ID Numbers:
- E05-CL-3004
First Posted:
Feb 15, 2012
Last Update Posted:
Nov 4, 2015
Last Verified:
Oct 1, 2015
Keywords provided by Astellas Pharma Inc
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Period Title: Overall Study | ||
| STARTED | 186 | 183 |
| COMPLETED | 177 | 175 |
| NOT COMPLETED | 9 | 8 |
Baseline Characteristics
| Arm/Group Title | Capsaicin 8% | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 | Total of all reporting groups |
| Overall Participants | 186 | 183 | 369 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
63.90
(10.64)
|
62.00
(10.81)
|
63.00
(10.75)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
72
38.7%
|
82
44.8%
|
154
41.7%
|
| Male |
114
61.3%
|
101
55.2%
|
215
58.3%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| White |
132
71%
|
131
71.6%
|
263
71.3%
|
| Black or African American |
36
19.4%
|
38
20.8%
|
74
20.1%
|
| Asian |
4
2.2%
|
4
2.2%
|
8
2.2%
|
| American Indian or Alaskan Native |
2
1.1%
|
1
0.5%
|
3
0.8%
|
| Native Hawaiian or Other Pacific Islander |
1
0.5%
|
2
1.1%
|
3
0.8%
|
| Other |
11
5.9%
|
7
3.8%
|
18
4.9%
|
| Duration of Painful Diabetic Peripheral Neuropathy (PDPN) (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
5.83
(4.01)
|
5.72
(3.98)
|
5.78
(3.99)
|
| Glycosylated Hemoglobin (HbA1c) (Percentage of Glycosylated Hemoglobin) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Percentage of Glycosylated Hemoglobin] |
7.39
(1.309)
|
7.23
(1.223)
|
7.31
(1.268)
|
| Average Pain Score (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
6.64
(1.416)
|
6.38
(1.473)
|
6.51
(1.449)
|
Outcome Measures
| Title | Percent Change in the Average Daily Pain Score From Baseline to Between Weeks 2 and 8 |
|---|---|
| Description | Percent change in the average daily pain score from baseline to between Weeks 2 and 8, measured using Question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN). Participants assessed their pain due to diabetes in the last 24 hours on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine). |
| Time Frame | Baseline to between Weeks 2 to 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| Mean (Standard Deviation) [percentage change] |
-27.44
(26.79)
|
-20.85
(28.92)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | All statistical comparisons were made using two-sided tests at the 5% significance level | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.025 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -6.6 | |
| Confidence Interval |
(2-Sided) 95% -12.3 to -0.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change in the Average Daily Pain Score From Baseline to Between Weeks 2 and 12 |
|---|---|
| Description | Percent Change in the Average Daily Pain Score from baseline to between Weeks 2 and 12 measured using Question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN). Participants assessed their pain due to diabetes in the last 24 hours on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine). |
| Time Frame | Baseline to between Weeks 2 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| Mean (Standard Deviation) [percentage change] |
-27.96
(27.25)
|
-21.00
(29.42)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | All statistical comparisons were made using two-sided tests at the 5% significance level. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.018 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -7.1 | |
| Confidence Interval |
(2-Sided) 95% -12.9 to -1.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Weekly Percent Change From Baseline in Average Daily Pain Score |
|---|---|
| Description | Weekly Percent Change from baseline in average daily pain score from baseline to Week 12 measured using Question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN). Participants assessed their pain due to diabetes in the last 24 hours on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine). |
| Time Frame | Baseline to Weeks 2, 3, 4, 5, 6, 7, 8, 9,10, 11 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT ); Baseline last observation carried forward (BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| Week 2 |
-22.97
(26.24)
|
-19.00
(27.99)
|
| Week 3 |
-27.17
(27.28)
|
-20.51
(29.96)
|
| Week 4 |
-28.18
(28.15)
|
-21.11
(30.52)
|
| Week 5 |
-28.35
(29.48)
|
-21.17
(30.26)
|
| Week 6 |
-27.87
(30.02)
|
-21.66
(31.45)
|
| Week 7 |
-29.03
(29.98)
|
-21.02
(32.50)
|
| Week 8 |
-28.53
(31.92)
|
-21.46
(31.29)
|
| Week 9 |
-28.61
(31.64)
|
-21.78
(31.05)
|
| Week 10 |
-28.17
(30.79)
|
-20.73
(32.39)
|
| Week 11 |
-29.04
(31.13)
|
-21.75
(32.58)
|
| Week 12 |
-29.64
(31.20)
|
-20.76
(33.33)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparison of capsaicin 8% and placebo for change from Baseline to Week 2. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.208 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -4.1 | |
| Confidence Interval |
(2-Sided) 95% -10.4 to 2.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparison of capsaicin 8% and placebo for change from Baseline to Week 3. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.036 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -6.7 | |
| Confidence Interval |
(2-Sided) 95% -13.1 to -0.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparison of capsaicin 8% and placebo for change from Baseline to Week 4. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.027 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -7.2 | |
| Confidence Interval |
(2-Sided) 95% -13.5 to -0.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparison of capsaicin 8% and placebo for change from Baseline to Week 5. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.024 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -7.3 | |
| Confidence Interval |
(2-Sided) 95% -13.6 to -1.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparison of capsaicin 8% and placebo for change from Baseline to Week 6. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.051 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -6.3 | |
| Confidence Interval |
(2-Sided) 95% -12.6 to 0.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparison of capsaicin 8% and placebo for change from Baseline to Week 7. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.012 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -8.1 | |
| Confidence Interval |
(2-Sided) 95% -14.4 to -1.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparison of capsaicin 8% and placebo for change from Baseline to Week 8. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.026 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -7.2 | |
| Confidence Interval |
(2-Sided) 95% -13.5 to -0.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparison of capsaicin 8% and placebo for change from Baseline to Week 9. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.032 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -6.9 | |
| Confidence Interval |
(2-Sided) 95% -13.2 to -0.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparison of capsaicin 8% and placebo for change from Baseline to Week 10. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.020 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -7.5 | |
| Confidence Interval |
(2-Sided) 95% -13.9 to -1.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparison of capsaicin 8% and placebo for change from Baseline to Week 11. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.022 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -7.4 | |
| Confidence Interval |
(2-Sided) 95% -13.7 to -1.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparison of capsaicin 8% and placebo for change from Baseline to Week 12. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -9.0 | |
| Confidence Interval |
(2-Sided) 95% -15.3 to -2.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline |
|---|---|
| Description | Weekly average of average daily pain score at Baseline and Weeks 2,4,8 and 12 measured using Question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN). Participants assessed their pain due to diabetes in the last 24 hours on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine). |
| Time Frame | Baseline and Weeks 2, 4, 8 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| Baseline |
6.64
(1.416)
|
6.38
(1.473)
|
| Week 2 |
5.14
(2.059)
|
5.14
(2.111)
|
| Week 4 |
4.83
(2.280)
|
5.02
(2.299)
|
| Week 8 |
4.78
(2.457)
|
5.01
(2.343)
|
| Week 12 |
4.73
(2.436)
|
5.08
(2.456)
|
| Title | Percentage of Participants With 30% Reduction in Average Daily Pain Score. |
|---|---|
| Description | Percentage of participants achieving 30% decrease in the average daily pain score in Weeks 2 and 8 and Weeks 2 and 12 measured using Question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN). Participants assessed their pain on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine). |
| Time Frame | Baseline, Weeks 2-8 and Weeks 2-12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT ); Baseline last observation carried forward(BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| 30% Pain Reduction-Week 2 to 8 |
74
39.8%
|
60
32.8%
|
| 30% Pain Reduction-Week 2 to 12 |
76
40.9%
|
58
31.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Percentage of participants with 30% reduction in average daily pain score assessed in Weeks 2-8. The comparison of the odds ratio of capsaicin 8% to placebo for percent change from baseline was performed using a logistic regression model. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.108 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Analysis of regression logistics model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.4 | |
| Confidence Interval |
(2-Sided) 95% 0.9 to 2.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Percentage of participants with 30% reduction in average daily pain score assessed in Weeks 2-12. The comparison of the odds ratio of capsaicin 8% to placebo for percent change from baseline was performed using a logistic regression model. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.050 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Analysis of regression logistics model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.5 | |
| Confidence Interval |
(2-Sided) 95% 1.0 to 2.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With 50% Reduction in Average Daily Pain Score. |
|---|---|
| Description | Percentage of participants achieving 50% decrease in the average daily pain score in Weeks 2 and 8 and Weeks 2 and 12 measured using Question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN). Participants assessed their pain on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine). |
| Time Frame | Baseline, Weeks 2-8 and Weeks 2-12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT ); Baseline last observation carried forward(BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| 50% Pain Reduction-Week 2 to 8 |
39
21%
|
33
18%
|
| 50% Pain Reduction-Week 2 to 12 |
41
22%
|
35
19.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Percentage of participants with 50% reduction in average daily pain score assessed in Weeks 2-8. The comparison of the odds ratio of capsaicin 8% to placebo for percent change from baseline was performed using a logistic regression model. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.403 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Analysis of regression logistics model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.2 | |
| Confidence Interval |
(2-Sided) 95% 0.7 to 2.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Percentage of participants with 50% reduction in average daily pain score assessed in Weeks 2-12. The comparison of the odds ratio of capsaicin 8% to placebo for percent change from baseline was performed using a logistic regression model. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.446 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Analysis of regression logistics model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.2 | |
| Confidence Interval |
(2-Sided) 95% 0.7 to 2.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 |
|---|---|
| Description | Overall participant status assessed using Patient Global Impression of Change (PGIC) self-assessment questionnaire which was used by participants to report on 7 categories listed as follows; Very Much Improved, Much Improved, Minimally Improved, No Change, Minimally Worse, Much Worse and Very Much Worse in Week 2 |
| Time Frame | Baseline to Week 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 183 | 180 |
| Very Much Improved |
10
5.4%
|
9
4.9%
|
| Much Improved |
49
26.3%
|
38
20.8%
|
| Minimally Improved |
72
38.7%
|
58
31.7%
|
| No Change |
45
24.2%
|
68
37.2%
|
| Minimally Worse |
3
1.6%
|
6
3.3%
|
| Much Worse |
3
1.6%
|
0
0%
|
| Very Much Worse |
1
0.5%
|
1
0.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparing the difference between capsaicin 8% and placebo for counts by category using a Cochran-Mantel-Haenszel test. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.072 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Analysis of Cochran-Mantel-Haenszel test model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Title | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 |
|---|---|
| Description | Overall participant status assessed using Patient Global Impression of Change (PGIC) self-assessment questionnaire which was used by participants to report on 7 categories listed as follows; Very Much Improved, Much Improved, Minimally Improved, No Change, Minimally Worse, Much Worse and Very Much Worse in Week 8 |
| Time Frame | Baseline to Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 180 | 172 |
| Very Much Improved |
20
10.8%
|
16
8.7%
|
| Much Improved |
51
27.4%
|
36
19.7%
|
| Minimally Improved |
58
31.2%
|
48
26.2%
|
| No Change |
47
25.3%
|
59
32.2%
|
| Minimally Worse |
4
2.2%
|
8
4.4%
|
| Much Worse |
0
0%
|
4
2.2%
|
| Very Much Worse |
0
0%
|
1
0.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparing the difference between capsaicin 8% and placebo for counts by category using a Cochran-Mantel-Haenszel test. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.075 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Analysis of Cochran-Mantel-Haenszel test model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Title | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 |
|---|---|
| Description | Overall participant status assessed using Patient Global Impression of Change (PGIC) self-assessment questionnaire which was used by participants to report on 7 categories listed as follows; Very Much Improved, Much Improved, Minimally Improved, No Change, Minimally Worse, Much Worse and Very Much Worse in Week 12 |
| Time Frame | Baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 168 | 172 |
| Very Much Improved |
23
12.4%
|
22
12%
|
| Much Improved |
45
24.2%
|
29
15.8%
|
| Minimally Improved |
39
21%
|
40
21.9%
|
| No Change |
50
26.9%
|
72
39.3%
|
| Minimally Worse |
9
4.8%
|
8
4.4%
|
| Much Worse |
2
1.1%
|
1
0.5%
|
| Very Much Worse |
0
0%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparing the difference between capsaicin 8% and placebo for counts by category using a Cochran-Mantel-Haenszel test. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.169 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Analysis of Cochran-Mantel-Haenszel test model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Title | Change From Baseline in the European Quality Of Life (QOL) Questionnaire in 5 Dimensions (EQ-5D) With Visual Analog Scale (VAS) to Weeks 2, 8 and 12 |
|---|---|
| Description | Change from Baseline in the European Quality Of Life (QOL) questionnaire in 5 dimensions (EQ-5D) with Visual Analog Scale (VAS) to Weeks 2, 8 and 12. EQ-5D self-reported questionnaire is used to measure health-related quality of life by measuring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D questionnaire includes a visual analog scale (VAS) which records participants self-rated health status on a graduated (0-100) scale with higher scores indicating higher Health-Related Quality of Life (HRQoL). |
| Time Frame | Baseline to Weeks 2, 8 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT); Baseline and Last Observation Carried Forward (BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| Week 8 [ N=180;N=170] |
4.0
(17.09)
|
3.5
(18.36)
|
| Week 12 [N=170; N=172] |
3.8
(17.94)
|
3.7
(19.08)
|
| Week 2 [N=184; N=181] |
1.3
(15.20)
|
3.9
(18.81)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | The statistical comparison between Baseline and Week 8 was made using two-sided tests at the 5% significance level. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.320 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 1.7 | |
| Confidence Interval |
(2-Sided) 95% -1.6 to 5.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | The statistical comparison between Baseline and Week 12 was made using two-sided tests at the 5% significance level. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.473 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 1.2 | |
| Confidence Interval |
(2-Sided) 95% -2.1 to 4.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | The statistical comparison between Baseline and Week 2 was made using two-sided tests at the 5% significance level. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.514 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 1.7 | |
| Confidence Interval |
(2-Sided) 95% -4.4 to 2.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Scale From Baseline to Weeks 2, 8 and 12 |
|---|---|
| Description | The Hospital Anxiety and Depression Scale (HADS) is a self-report scale developed for the assessment of anxiety and depression, that contain 14 items rated on a 4-point Likert-type scale. There are 2 subscales,one assessing depression and the other anxiety. The 7-item depression and anxiety subscales yield scores of 0 to 21 that are interpreted with the following cut-off points: 0 to 7, normal; 8 to 10, mild mood disturbance; 11 to 14, moderate mood disturbance; and 15 to 21, severe mood disturbance. |
| Time Frame | Baseline to Weeks 2, 8 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT); Baseline and Last Observation Carried Forward (BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| Week 2 [N=183; N=180] |
-0.4
(2.57)
|
-0.5
(2.74)
|
| Week 8 [N=178; N=171] |
-0.7
(2.72)
|
-0.6
(3.11)
|
| Week 12 [N=169; N=169] |
-0.9
(2.90)
|
-0.9
(3.03)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparing the difference between capsaicin 8% and placebo for change from Baseline at Week 2 was completed using ANCOVA model. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.719 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparing the difference between capsaicin 8% and placebo for change from Baseline at Week 8 was completed using ANCOVA model. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.334 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 0.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparing the difference between capsaicin 8% and placebo for change from Baseline at Week 12 was completed using ANCOVA model. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.726 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Hospital Anxiety and Depression Scale (HADS) Depression Scale From Baseline to Weeks 2, 8 and 12. |
|---|---|
| Description | The Hospital Anxiety and Depression Scale (HADS) is a self-report scale developed for the assessment of anxiety and depression, it contains 14 items rated on a 4-point Likert-type scale. There are 2 subscales,one assessing depression and the other anxiety. The 7-item depression and anxiety subscales yield scores of 0 to 21 that are interpreted with the following cut-off points: 0 to 7, normal; 8 to 10, mild mood disturbance; 11 to 14, moderate mood disturbance; and 15 to 21, severe mood disturbance. |
| Time Frame | Baseline to Weeks 2, 8 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT); Baseline and Last Observation Carried Forward (BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| Week 2 [ N=184; N=181] |
-0.6
(2.39)
|
-0.6
(2.73)
|
| Week 8 [N=180; N=171] |
-0.7
(2.42)
|
-0.4
(3.15)
|
| Week 12 [N=169; N=171] |
-0.8
(2.41)
|
-0.6
(3.24)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparing the difference between capsaicin 8% and placebo for change from Baseline at Week 2 was completed using ANCOVA model. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.841 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparing the difference between capsaicin 8% and placebo for change from Baseline at Week 8 was completed using ANCOVA model. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.171 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -0.9 to 0.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | Comparing the difference between capsaicin 8% and placebo for change from Baseline at Week 12 was completed using ANCOVA model. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.595 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment, gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 |
|---|---|
| Description | Treatment satisfaction assessment based on Self-Assessment Treatment (SAT II) questionnaire and the question "Over the past 7 days, how much has the study treatment improved your pain level?" |
| Time Frame | Baseline, Weeks 8 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| Week 8 [N=177; N=170] [Not at all] |
59
31.7%
|
82
44.8%
|
| Week 8 [N=177; N=170] [Slightly Better] |
35
18.8%
|
33
18%
|
| Week 8 [N=177; N=170] [Moderately Better] |
37
19.9%
|
21
11.5%
|
| Week 8 [N=177; N=170] [Quite a Bit Better] |
30
16.1%
|
21
11.5%
|
| Week 8 [N=177; N=170] [Very Much Better] |
16
8.6%
|
13
7.1%
|
| Week 12 [N=166; N=171] [Not at all] |
69
37.1%
|
91
49.7%
|
| Week 12 [N=166; N=171] [Slightly Better] |
30
16.1%
|
38
20.8%
|
| Week 12 [N=166; N=171] [Moderately Better] |
23
12.4%
|
12
6.6%
|
| Week 12 [N=166; N=171] [Quite a Bit Better] |
29
15.6%
|
14
7.7%
|
| Week 12 [N=166; N=171][Very Much Better] |
15
8.1%
|
16
8.7%
|
| Title | Percent Change in Average Sleep Interference Score From Baseline to Between Weeks 2-8 and Weeks 2-12 |
|---|---|
| Description | Percent change in average sleep interference was measured by Question 9F of the Brief Pain Inventory-Diabetic Neuropathy (BPI DN) and was used to assess pain and sleep interference index. Daily sleep interference rating scale consists of an 11-point numerical scale with which the patient describes how pain related to diabetes has interfered with their sleep during the past 24 hours. On a scale 0 identifies "pain does not interfere with sleep" and 10 identifies "pain completely interferes with sleep". Average sleep interference score is assessed from baseline to Weeks 2-8 and Weeks 2-12. |
| Time Frame | Baseline, Weeks 2-8 and Weeks 2-12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used. |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| Week 2-8 |
-33.12
(33.683)
|
-24.15
(45.019)
|
| Week 2-12 |
-33.99
(33.566)
|
-24.67
(43.188)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | All statistical comparisons were made using two-sided tests at the 5% significance level. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.030 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment,gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -9.0 | |
| Confidence Interval |
(2-Sided) 95% -17.2 to -0.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Capsaicin 8%, Placebo |
|---|---|---|
| Comments | All statistical comparisons were made using two-sided tests at the 5% significance level. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.020 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance model including treatment,gender, pain score at baseline, HbA1c at screening and site as factors/covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -9.5 | |
| Confidence Interval |
(2-Sided) 95% -17.4 to -1.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Tolerability of Patch Application Assessed by Dermal Assessment on Day 1, 15 Minutes and 60 Minutes After Patch Removal. |
|---|---|
| Description | Tolerability of patch application was assessed by dermal assessment (0 to 7 point severity score on Dermal Assessment Scale). Data reported is based on the number of participants in the combined category with a score ≥ 4 (Definite edema or higher), 15 and 60 minutes after patch removal. |
| Time Frame | Day 1, 15 minutes and 60 minutes after patch removal |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAF) |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| 15 minutes after patch removal [N=185,N=180] |
0
0%
|
2
1.1%
|
| 60 minutes after patch removal [N=185,N=179] |
0
0%
|
2
1.1%
|
| Title | Change From Pre-application in"Pain Now" Score |
|---|---|
| Description | Change from pre-application in"Pain Now" score was measured on a scale from 0-10 where 0 equates to "No Pain" and 10 to "Pain as bad as you can imagine". Participants were asked to provide pain ratings relative only to the area of pain undergoing treatment. |
| Time Frame | Pre-application and 15 minutes and 60 minutes after patch removal |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAF) |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| 15 minutes after patch removal [N=185; N=183] |
-1.6
(2.49)
|
-2.0
(2.08)
|
| 60 minutes after patch removal [N=185; N=182] |
-1.8
(2.57)
|
-2.2
(2.07)
|
| Title | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 |
|---|---|
| Description | Summarized number of participants who used Rescue Pain Medications for Pain |
| Time Frame | Days 1 - 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAF) |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| Overall |
35
18.8%
|
10
5.5%
|
| Analgesics |
22
11.8%
|
9
4.9%
|
| Anilides |
20
10.8%
|
9
4.9%
|
| Natural opium alkaloids |
14
7.5%
|
4
2.2%
|
| Other opioids |
2
1.1%
|
0
0%
|
| Salicylic acid and derivatives |
1
0.5%
|
0
0%
|
| Antiinflammatory and antirheumatic products |
15
8.1%
|
1
0.5%
|
| Propionic acid derivatives |
15
8.1%
|
1
0.5%
|
| Other gynecologicals |
15
8.1%
|
1
0.5%
|
| Antiinflammatory products vaginal administration |
15
8.1%
|
1
0.5%
|
| Topical products for joint and muscular pain |
16
8.6%
|
1
0.5%
|
| Antiinflammatory preparations, nonsteroids for top |
15
8.1%
|
1
0.5%
|
| Preparations with salicylic acid derivatives |
1
0.5%
|
0
0%
|
| Title | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 |
|---|---|
| Description | Number of patients assessed for Safety through Adverse Events (AE) and Serious Adverse Events (SAE), vital signs, and laboratory analyses from baseline to week 12 |
| Time Frame | Baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAF) |
| Arm/Group Title | Capsaicin 8% | Placebo |
|---|---|---|
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 |
| Measure Participants | 186 | 183 |
| Treatment-emergent adverse events (TEAEs) |
87
46.8%
|
62
33.9%
|
| Drug-related TEAEs |
65
34.9%
|
23
12.6%
|
| Deaths |
0
0%
|
0
0%
|
| Serious TEAEs |
2
1.1%
|
7
3.8%
|
| Drug-related serious TEAEs |
0
0%
|
0
0%
|
| TEAEs permanent discontinuation of study drug |
0
0%
|
0
0%
|
| Drug-related TEAEs to permanent discontinuation |
0
0%
|
0
0%
|
| Application site reactions |
63
33.9%
|
15
8.2%
|
Adverse Events
| Time Frame | Adverse Events were reported from the first application of study drug to Week 12 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Capsaicin 8% | Placebo | ||
| Arm/Group Description | Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 | ||
All Cause Mortality |
||||
| Capsaicin 8% | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Capsaicin 8% | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/186 (1.1%) | 7/183 (3.8%) | ||
| Cardiac disorders | ||||
| Coronary artery disease | 0/186 (0%) | 1/183 (0.5%) | ||
| Myocardial infarction | 0/186 (0%) | 1/183 (0.5%) | ||
| General disorders | ||||
| Noncardiac chest pain | 0/186 (0%) | 1/183 (0.5%) | ||
| Infections and infestations | ||||
| Postprocedural infection | 0/186 (0%) | 1/183 (0.5%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/186 (0.5%) | 0/183 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Oesophageal carcinoma | 0/186 (0%) | 1/183 (0.5%) | ||
| Nervous system disorders | ||||
| Convulsion | 1/186 (0.5%) | 0/183 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic obstructive pulmonary disease | 0/186 (0%) | 2/183 (1.1%) | ||
| Surgical and medical procedures | ||||
| Knee arthroplasty | 0/186 (0%) | 1/183 (0.5%) | ||
| Vascular disorders | ||||
| Hypotension | 0/186 (0%) | 1/183 (0.5%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Capsaicin 8% | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 61/186 (32.8%) | 18/183 (9.8%) | ||
| General disorders | ||||
| Application site pain | 18/186 (9.7%) | 4/183 (2.2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Pain in extremity | 20/186 (10.8%) | 10/183 (5.5%) | ||
| Nervous system disorders | ||||
| Burning sensation | 26/186 (14%) | 5/183 (2.7%) | ||
Limitations/Caveats
Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Institute and/or Principal Investigator may publish or present trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript at least 30 days prior to publication to ensure that no confidential information of Sponsor is included in the document. Sponsor may delay the publication for an additional 60 days to seek patent protection.
Results Point of Contact
| Name/Title | Medical Science Director, Global Medical Science |
|---|---|
| Organization | Astellas Pharma Global Development |
| Phone | +31(0)715454002 |
| Astellas.resultsdisclosure@astellas.com |
Responsible Party:
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01533428
Other Study ID Numbers:
- E05-CL-3004
First Posted:
Feb 15, 2012
Last Update Posted:
Nov 4, 2015
Last Verified:
Oct 1, 2015