Diabetic Peripheral Neuropathy, Pain
Conditions
Keywords
Painful Diabetic Peripheral Neuropathy,, Capsaicin 8% transdermal delivery system
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.
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.
Interventions
DRUGCapsaicin 8%
Capsaicin 8% transdermal delivery system
DRUGPlacebo
Placebo Patch
Sponsors
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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 inPain Now Score | Pre-application and 15 minutes and 60 minutes after patch removal | Change from pre-application inPain 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 |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Capsaicin 8% Capsaicin 8% patch was applied for 30 minutes to the painful area(s) on Day 1 | 186 |
| Placebo Placebo patch was applied for 30 minutes to the painful area(s) on Day 1 | 183 |
| Total | 369 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 6 |
Baseline characteristics
| Characteristic | Capsaicin 8% | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 63.90 years STANDARD_DEVIATION 10.64 | 62.00 years STANDARD_DEVIATION 10.81 | 63.00 years STANDARD_DEVIATION 10.75 |
| Average Pain Score | 6.64 units on a scale STANDARD_DEVIATION 1.416 | 6.38 units on a scale STANDARD_DEVIATION 1.473 | 6.51 units on a scale STANDARD_DEVIATION 1.449 |
| Duration of Painful Diabetic Peripheral Neuropathy (PDPN) | 5.83 years STANDARD_DEVIATION 4.01 | 5.72 years STANDARD_DEVIATION 3.98 | 5.78 years STANDARD_DEVIATION 3.99 |
| Glycosylated Hemoglobin (HbA1c) | 7.39 Percentage of Glycosylated Hemoglobin STANDARD_DEVIATION 1.309 | 7.23 Percentage of Glycosylated Hemoglobin STANDARD_DEVIATION 1.223 | 7.31 Percentage of Glycosylated Hemoglobin STANDARD_DEVIATION 1.268 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Asian | 4 participants | 4 participants | 8 participants |
| Race/Ethnicity, Customized Black or African American | 36 participants | 38 participants | 74 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Other | 11 participants | 7 participants | 18 participants |
| Race/Ethnicity, Customized White | 132 participants | 131 participants | 263 participants |
| Sex: Female, Male Female | 72 Participants | 82 Participants | 154 Participants |
| Sex: Female, Male Male | 114 Participants | 101 Participants | 215 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 61 / 186 | 18 / 183 |
| serious Total, serious adverse events | 2 / 186 | 7 / 183 |
Outcome results
Primary
Percent Change in the Average Daily Pain Score From Baseline to Between Weeks 2 and 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).
Time frame: Baseline to between Weeks 2 to 8
Population: Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Capsaicin 8% | Percent Change in the Average Daily Pain Score From Baseline to Between Weeks 2 and 8 | -27.44 percentage change | Standard Deviation 26.79 |
| Placebo | Percent Change in the Average Daily Pain Score From Baseline to Between Weeks 2 and 8 | -20.85 percentage change | Standard Deviation 28.92 |
Comparison: All statistical comparisons were made using two-sided tests at the 5% significance levelp-value: 0.02595% CI: [-12.3, -0.8]ANCOVA
Secondary
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
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
Population: Intention to Treat (ITT); Baseline and Last Observation Carried Forward (BLOCF) imputation was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capsaicin 8% | 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 | Week 8 [ N=180;N=170] | 4.0 units on a scale | Standard Deviation 17.09 |
| Capsaicin 8% | 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 | Week 12 [N=170; N=172] | 3.8 units on a scale | Standard Deviation 17.94 |
| Capsaicin 8% | 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 | Week 2 [N=184; N=181] | 1.3 units on a scale | Standard Deviation 15.2 |
| Placebo | 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 | Week 8 [ N=180;N=170] | 3.5 units on a scale | Standard Deviation 18.36 |
| Placebo | 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 | Week 12 [N=170; N=172] | 3.7 units on a scale | Standard Deviation 19.08 |
| Placebo | 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 | Week 2 [N=184; N=181] | 3.9 units on a scale | Standard Deviation 18.81 |
Comparison: The statistical comparison between Baseline and Week 8 was made using two-sided tests at the 5% significance level.p-value: 0.3295% CI: [-1.6, 5]ANCOVA
Comparison: The statistical comparison between Baseline and Week 12 was made using two-sided tests at the 5% significance level.p-value: 0.47395% CI: [-2.1, 4.5]ANCOVA
Comparison: The statistical comparison between Baseline and Week 2 was made using two-sided tests at the 5% significance level.p-value: 0.51495% CI: [-4.4, 2.2]ANCOVA
Secondary
Change From Pre-application inPain Now Score
Change from pre-application inPain 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
Population: Safety Analysis Set (SAF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capsaicin 8% | Change From Pre-application inPain Now Score | 15 minutes after patch removal [N=185; N=183] | -1.6 units on a scale | Standard Deviation 2.49 |
| Capsaicin 8% | Change From Pre-application inPain Now Score | 60 minutes after patch removal [N=185; N=182] | -1.8 units on a scale | Standard Deviation 2.57 |
| Placebo | Change From Pre-application inPain Now Score | 15 minutes after patch removal [N=185; N=183] | -2.0 units on a scale | Standard Deviation 2.08 |
| Placebo | Change From Pre-application inPain Now Score | 60 minutes after patch removal [N=185; N=182] | -2.2 units on a scale | Standard Deviation 2.07 |
Secondary
Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Scale From 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.
Time frame: Baseline to Weeks 2, 8 and 12
Population: Intention to Treat (ITT); Baseline and Last Observation Carried Forward (BLOCF) imputation was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capsaicin 8% | Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Scale From Baseline to Weeks 2, 8 and 12 | Week 2 [N=183; N=180] | -0.4 units on a scale | Standard Deviation 2.57 |
| Capsaicin 8% | Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Scale From Baseline to Weeks 2, 8 and 12 | Week 8 [N=178; N=171] | -0.7 units on a scale | Standard Deviation 2.72 |
| Capsaicin 8% | Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Scale From Baseline to Weeks 2, 8 and 12 | Week 12 [N=169; N=169] | -0.9 units on a scale | Standard Deviation 2.9 |
| Placebo | Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Scale From Baseline to Weeks 2, 8 and 12 | Week 2 [N=183; N=180] | -0.5 units on a scale | Standard Deviation 2.74 |
| Placebo | Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Scale From Baseline to Weeks 2, 8 and 12 | Week 8 [N=178; N=171] | -0.6 units on a scale | Standard Deviation 3.11 |
| Placebo | Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Scale From Baseline to Weeks 2, 8 and 12 | Week 12 [N=169; N=169] | -0.9 units on a scale | Standard Deviation 3.03 |
Comparison: Comparing the difference between capsaicin 8% and placebo for change from Baseline at Week 2 was completed using ANCOVA model.p-value: 0.71995% CI: [-0.5, 0.7]ANCOVA
Comparison: Comparing the difference between capsaicin 8% and placebo for change from Baseline at Week 8 was completed using ANCOVA model.p-value: 0.33495% CI: [-0.8, 0.3]ANCOVA
Comparison: Comparing the difference between capsaicin 8% and placebo for change from Baseline at Week 12 was completed using ANCOVA model.p-value: 0.72695% CI: [-0.7, 0.5]ANCOVA
Secondary
Change in Hospital Anxiety and Depression Scale (HADS) Depression Scale From 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.
Time frame: Baseline to Weeks 2, 8 and 12
Population: Intention to Treat (ITT); Baseline and Last Observation Carried Forward (BLOCF) imputation was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capsaicin 8% | Change in Hospital Anxiety and Depression Scale (HADS) Depression Scale From Baseline to Weeks 2, 8 and 12. | Week 2 [ N=184; N=181] | -0.6 units on a scale | Standard Deviation 2.39 |
| Capsaicin 8% | Change in Hospital Anxiety and Depression Scale (HADS) Depression Scale From Baseline to Weeks 2, 8 and 12. | Week 8 [N=180; N=171] | -0.7 units on a scale | Standard Deviation 2.42 |
| Capsaicin 8% | Change in Hospital Anxiety and Depression Scale (HADS) Depression Scale From Baseline to Weeks 2, 8 and 12. | Week 12 [N=169; N=171] | -0.8 units on a scale | Standard Deviation 2.41 |
| Placebo | Change in Hospital Anxiety and Depression Scale (HADS) Depression Scale From Baseline to Weeks 2, 8 and 12. | Week 2 [ N=184; N=181] | -0.6 units on a scale | Standard Deviation 2.73 |
| Placebo | Change in Hospital Anxiety and Depression Scale (HADS) Depression Scale From Baseline to Weeks 2, 8 and 12. | Week 8 [N=180; N=171] | -0.4 units on a scale | Standard Deviation 3.15 |
| Placebo | Change in Hospital Anxiety and Depression Scale (HADS) Depression Scale From Baseline to Weeks 2, 8 and 12. | Week 12 [N=169; N=171] | -0.6 units on a scale | Standard Deviation 3.24 |
Comparison: Comparing the difference between capsaicin 8% and placebo for change from Baseline at Week 2 was completed using ANCOVA model.p-value: 0.84195% CI: [-0.6, 0.5]ANCOVA
Comparison: Comparing the difference between capsaicin 8% and placebo for change from Baseline at Week 8 was completed using ANCOVA model.p-value: 0.17195% CI: [-0.9, 0.2]ANCOVA
Comparison: Comparing the difference between capsaicin 8% and placebo for change from Baseline at Week 12 was completed using ANCOVA model.p-value: 0.59595% CI: [-0.7, 0.4]ANCOVA
Secondary
Number of Participants Who Used Rescue Pain Medication Days 1 Through 5
Summarized number of participants who used Rescue Pain Medications for Pain
Time frame: Days 1 - 5
Population: Safety Analysis Set (SAF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Overall | 35 participants |
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Analgesics | 22 participants |
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Anilides | 20 participants |
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Natural opium alkaloids | 14 participants |
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Other opioids | 2 participants |
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Salicylic acid and derivatives | 1 participants |
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Antiinflammatory and antirheumatic products | 15 participants |
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Propionic acid derivatives | 15 participants |
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Other gynecologicals | 15 participants |
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Antiinflammatory products vaginal administration | 15 participants |
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Topical products for joint and muscular pain | 16 participants |
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Antiinflammatory preparations, nonsteroids for top | 15 participants |
| Capsaicin 8% | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Preparations with salicylic acid derivatives | 1 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Preparations with salicylic acid derivatives | 0 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Topical products for joint and muscular pain | 1 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Overall | 10 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Antiinflammatory and antirheumatic products | 1 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Analgesics | 9 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Antiinflammatory products vaginal administration | 1 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Anilides | 9 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Propionic acid derivatives | 1 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Natural opium alkaloids | 4 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Antiinflammatory preparations, nonsteroids for top | 1 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Other opioids | 0 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Other gynecologicals | 1 participants |
| Placebo | Number of Participants Who Used Rescue Pain Medication Days 1 Through 5 | Salicylic acid and derivatives | 0 participants |
Secondary
Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in 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
Time frame: Baseline to Week 12
Population: Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | Minimally Improved | 39 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | Minimally Worse | 9 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | Much Improved | 45 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | Much Worse | 2 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | No Change | 50 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | Very Much Worse | 0 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | Very Much Improved | 23 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | Very Much Worse | 0 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | Very Much Improved | 22 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | Much Improved | 29 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | Minimally Improved | 40 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | No Change | 72 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | Minimally Worse | 8 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12 | Much Worse | 1 participants |
Comparison: Comparing the difference between capsaicin 8% and placebo for counts by category using a Cochran-Mantel-Haenszel test.p-value: 0.169Cochran-Mantel-Haenszel
Secondary
Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in 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
Time frame: Baseline to Week 2
Population: Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | Minimally Improved | 72 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | Minimally Worse | 3 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | Much Improved | 49 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | Much Worse | 3 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | No Change | 45 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | Very Much Worse | 1 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | Very Much Improved | 10 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | Very Much Worse | 1 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | Very Much Improved | 9 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | Much Improved | 38 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | Minimally Improved | 58 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | No Change | 68 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | Minimally Worse | 6 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2 | Much Worse | 0 participants |
Comparison: Comparing the difference between capsaicin 8% and placebo for counts by category using a Cochran-Mantel-Haenszel test.p-value: 0.072Cochran-Mantel-Haenszel
Secondary
Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in 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
Time frame: Baseline to Week 8
Population: Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | Minimally Improved | 58 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | Minimally Worse | 4 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | Much Improved | 51 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | Much Worse | 0 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | No Change | 47 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | Very Much Worse | 0 participants |
| Capsaicin 8% | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | Very Much Improved | 20 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | Very Much Worse | 1 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | Very Much Improved | 16 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | Much Improved | 36 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | Minimally Improved | 48 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | No Change | 59 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | Minimally Worse | 8 participants |
| Placebo | Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8 | Much Worse | 4 participants |
Comparison: Comparing the difference between capsaicin 8% and placebo for counts by category using a Cochran-Mantel-Haenszel test.p-value: 0.075Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With 30% Reduction in Average Daily Pain Score.
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
Population: Intention to Treat (ITT ); Baseline last observation carried forward(BLOCF) imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capsaicin 8% | Percentage of Participants With 30% Reduction in Average Daily Pain Score. | 30% Pain Reduction-Week 2 to 8 | 74 percentage of participants |
| Capsaicin 8% | Percentage of Participants With 30% Reduction in Average Daily Pain Score. | 30% Pain Reduction-Week 2 to 12 | 76 percentage of participants |
| Placebo | Percentage of Participants With 30% Reduction in Average Daily Pain Score. | 30% Pain Reduction-Week 2 to 8 | 60 percentage of participants |
| Placebo | Percentage of Participants With 30% Reduction in Average Daily Pain Score. | 30% Pain Reduction-Week 2 to 12 | 58 percentage of participants |
Comparison: 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.p-value: 0.10895% CI: [0.9, 2.2]Regression, Logistic
Comparison: 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.p-value: 0.0595% CI: [1, 2.4]Regression, Logistic
Secondary
Percentage of Participants With 50% Reduction in Average Daily Pain Score.
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
Population: Intention to Treat (ITT ); Baseline last observation carried forward(BLOCF) imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capsaicin 8% | Percentage of Participants With 50% Reduction in Average Daily Pain Score. | 50% Pain Reduction-Week 2 to 8 | 39 percentage of participants |
| Capsaicin 8% | Percentage of Participants With 50% Reduction in Average Daily Pain Score. | 50% Pain Reduction-Week 2 to 12 | 41 percentage of participants |
| Placebo | Percentage of Participants With 50% Reduction in Average Daily Pain Score. | 50% Pain Reduction-Week 2 to 8 | 33 percentage of participants |
| Placebo | Percentage of Participants With 50% Reduction in Average Daily Pain Score. | 50% Pain Reduction-Week 2 to 12 | 35 percentage of participants |
Comparison: 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.p-value: 0.40395% CI: [0.7, 2.1]Regression, Logistic
Comparison: 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.p-value: 0.44695% CI: [0.7, 2]Regression, Logistic
Secondary
Percent Change in Average Sleep Interference Score From Baseline to Between 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.
Time frame: Baseline, Weeks 2-8 and Weeks 2-12
Population: Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capsaicin 8% | Percent Change in Average Sleep Interference Score From Baseline to Between Weeks 2-8 and Weeks 2-12 | Week 2-8 | -33.12 percentage of change | Standard Deviation 33.683 |
| Capsaicin 8% | Percent Change in Average Sleep Interference Score From Baseline to Between Weeks 2-8 and Weeks 2-12 | Week 2-12 | -33.99 percentage of change | Standard Deviation 33.566 |
| Placebo | Percent Change in Average Sleep Interference Score From Baseline to Between Weeks 2-8 and Weeks 2-12 | Week 2-8 | -24.15 percentage of change | Standard Deviation 45.019 |
| Placebo | Percent Change in Average Sleep Interference Score From Baseline to Between Weeks 2-8 and Weeks 2-12 | Week 2-12 | -24.67 percentage of change | Standard Deviation 43.188 |
Comparison: All statistical comparisons were made using two-sided tests at the 5% significance level.p-value: 0.0395% CI: [-17.2, -0.9]ANCOVA
Comparison: All statistical comparisons were made using two-sided tests at the 5% significance level.p-value: 0.0295% CI: [-17.4, -1.5]ANCOVA
Secondary
Percent Change in the Average Daily Pain Score From 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).
Time frame: Baseline to between Weeks 2 and 12
Population: Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Capsaicin 8% | Percent Change in the Average Daily Pain Score From Baseline to Between Weeks 2 and 12 | -27.96 percentage change | Standard Deviation 27.25 |
| Placebo | Percent Change in the Average Daily Pain Score From Baseline to Between Weeks 2 and 12 | -21.00 percentage change | Standard Deviation 29.42 |
Comparison: All statistical comparisons were made using two-sided tests at the 5% significance level.p-value: 0.01895% CI: [-12.9, -1.2]ANCOVA
Secondary
Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From 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
Time frame: Baseline to Week 12
Population: Safety Analysis Set (SAF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capsaicin 8% | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Treatment-emergent adverse events (TEAEs) | 87 participants |
| Capsaicin 8% | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Drug-related TEAEs | 65 participants |
| Capsaicin 8% | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Deaths | 0 participants |
| Capsaicin 8% | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Serious TEAEs | 2 participants |
| Capsaicin 8% | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Drug-related serious TEAEs | 0 participants |
| Capsaicin 8% | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | TEAEs permanent discontinuation of study drug | 0 participants |
| Capsaicin 8% | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Drug-related TEAEs to permanent discontinuation | 0 participants |
| Capsaicin 8% | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Application site reactions | 63 participants |
| Placebo | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Application site reactions | 15 participants |
| Placebo | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Treatment-emergent adverse events (TEAEs) | 62 participants |
| Placebo | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Drug-related serious TEAEs | 0 participants |
| Placebo | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Drug-related TEAEs | 23 participants |
| Placebo | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Drug-related TEAEs to permanent discontinuation | 0 participants |
| Placebo | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Deaths | 0 participants |
| Placebo | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | TEAEs permanent discontinuation of study drug | 0 participants |
| Placebo | Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12 | Serious TEAEs | 7 participants |
Secondary
Tolerability of Patch Application Assessed by Dermal Assessment on 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.
Time frame: Day 1, 15 minutes and 60 minutes after patch removal
Population: Safety Analysis Set (SAF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capsaicin 8% | Tolerability of Patch Application Assessed by Dermal Assessment on Day 1, 15 Minutes and 60 Minutes After Patch Removal. | 15 minutes after patch removal [N=185,N=180] | 0 participants |
| Capsaicin 8% | Tolerability of Patch Application Assessed by Dermal Assessment on Day 1, 15 Minutes and 60 Minutes After Patch Removal. | 60 minutes after patch removal [N=185,N=179] | 0 participants |
| Placebo | Tolerability of Patch Application Assessed by Dermal Assessment on Day 1, 15 Minutes and 60 Minutes After Patch Removal. | 15 minutes after patch removal [N=185,N=180] | 2 participants |
| Placebo | Tolerability of Patch Application Assessed by Dermal Assessment on Day 1, 15 Minutes and 60 Minutes After Patch Removal. | 60 minutes after patch removal [N=185,N=179] | 2 participants |
Secondary
Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at 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?
Time frame: Baseline, Weeks 8 and 12
Population: Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capsaicin 8% | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 8 [N=177; N=170] [Not at all] | 59 participants |
| Capsaicin 8% | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 8 [N=177; N=170] [Slightly Better] | 35 participants |
| Capsaicin 8% | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 8 [N=177; N=170] [Moderately Better] | 37 participants |
| Capsaicin 8% | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 8 [N=177; N=170] [Quite a Bit Better] | 30 participants |
| Capsaicin 8% | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 8 [N=177; N=170] [Very Much Better] | 16 participants |
| Capsaicin 8% | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 12 [N=166; N=171] [Not at all] | 69 participants |
| Capsaicin 8% | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 12 [N=166; N=171] [Slightly Better] | 30 participants |
| Capsaicin 8% | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 12 [N=166; N=171] [Moderately Better] | 23 participants |
| Capsaicin 8% | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 12 [N=166; N=171] [Quite a Bit Better] | 29 participants |
| Capsaicin 8% | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 12 [N=166; N=171][Very Much Better] | 15 participants |
| Placebo | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 12 [N=166; N=171] [Moderately Better] | 12 participants |
| Placebo | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 8 [N=177; N=170] [Not at all] | 82 participants |
| Placebo | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 12 [N=166; N=171] [Not at all] | 91 participants |
| Placebo | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 8 [N=177; N=170] [Slightly Better] | 33 participants |
| Placebo | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 12 [N=166; N=171][Very Much Better] | 16 participants |
| Placebo | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 8 [N=177; N=170] [Moderately Better] | 21 participants |
| Placebo | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 12 [N=166; N=171] [Slightly Better] | 38 participants |
| Placebo | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 8 [N=177; N=170] [Quite a Bit Better] | 21 participants |
| Placebo | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 12 [N=166; N=171] [Quite a Bit Better] | 14 participants |
| Placebo | Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12 | Week 8 [N=177; N=170] [Very Much Better] | 13 participants |
Secondary
Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline
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
Population: Intention to Treat (ITT); Baseline Last Observation Carried Forward (BLOCF) imputation was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capsaicin 8% | Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline | Week 2 | 5.14 units on a scale | Standard Deviation 2.059 |
| Capsaicin 8% | Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline | Week 8 | 4.78 units on a scale | Standard Deviation 2.457 |
| Capsaicin 8% | Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline | Week 4 | 4.83 units on a scale | Standard Deviation 2.28 |
| Capsaicin 8% | Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline | Week 12 | 4.73 units on a scale | Standard Deviation 2.436 |
| Capsaicin 8% | Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline | Baseline | 6.64 units on a scale | Standard Deviation 1.416 |
| Placebo | Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline | Week 12 | 5.08 units on a scale | Standard Deviation 2.456 |
| Placebo | Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline | Baseline | 6.38 units on a scale | Standard Deviation 1.473 |
| Placebo | Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline | Week 2 | 5.14 units on a scale | Standard Deviation 2.111 |
| Placebo | Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline | Week 4 | 5.02 units on a scale | Standard Deviation 2.299 |
| Placebo | Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline | Week 8 | 5.01 units on a scale | Standard Deviation 2.343 |
Secondary
Weekly Percent Change From Baseline in Average Daily Pain Score
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
Population: Intention to Treat (ITT ); Baseline last observation carried forward (BLOCF) imputation was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capsaicin 8% | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 5 | -28.35 percentage change | Standard Deviation 29.48 |
| Capsaicin 8% | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 8 | -28.53 percentage change | Standard Deviation 31.92 |
| Capsaicin 8% | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 4 | -28.18 percentage change | Standard Deviation 28.15 |
| Capsaicin 8% | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 9 | -28.61 percentage change | Standard Deviation 31.64 |
| Capsaicin 8% | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 6 | -27.87 percentage change | Standard Deviation 30.02 |
| Capsaicin 8% | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 10 | -28.17 percentage change | Standard Deviation 30.79 |
| Capsaicin 8% | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 3 | -27.17 percentage change | Standard Deviation 27.28 |
| Capsaicin 8% | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 11 | -29.04 percentage change | Standard Deviation 31.13 |
| Capsaicin 8% | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 7 | -29.03 percentage change | Standard Deviation 29.98 |
| Capsaicin 8% | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 12 | -29.64 percentage change | Standard Deviation 31.2 |
| Capsaicin 8% | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 2 | -22.97 percentage change | Standard Deviation 26.24 |
| Placebo | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 12 | -20.76 percentage change | Standard Deviation 33.33 |
| Placebo | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 2 | -19.00 percentage change | Standard Deviation 27.99 |
| Placebo | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 3 | -20.51 percentage change | Standard Deviation 29.96 |
| Placebo | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 4 | -21.11 percentage change | Standard Deviation 30.52 |
| Placebo | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 5 | -21.17 percentage change | Standard Deviation 30.26 |
| Placebo | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 6 | -21.66 percentage change | Standard Deviation 31.45 |
| Placebo | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 7 | -21.02 percentage change | Standard Deviation 32.5 |
| Placebo | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 8 | -21.46 percentage change | Standard Deviation 31.29 |
| Placebo | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 9 | -21.78 percentage change | Standard Deviation 31.05 |
| Placebo | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 10 | -20.73 percentage change | Standard Deviation 32.39 |
| Placebo | Weekly Percent Change From Baseline in Average Daily Pain Score | Week 11 | -21.75 percentage change | Standard Deviation 32.58 |
Comparison: Comparison of capsaicin 8% and placebo for change from Baseline to Week 2.p-value: 0.20895% CI: [-10.4, 2.3]ANCOVA
Comparison: Comparison of capsaicin 8% and placebo for change from Baseline to Week 3.p-value: 0.03695% CI: [-13.1, -0.4]ANCOVA
Comparison: Comparison of capsaicin 8% and placebo for change from Baseline to Week 4.p-value: 0.02795% CI: [-13.5, -0.8]ANCOVA
Comparison: Comparison of capsaicin 8% and placebo for change from Baseline to Week 5.p-value: 0.02495% CI: [-13.6, -1]ANCOVA
Comparison: Comparison of capsaicin 8% and placebo for change from Baseline to Week 6.p-value: 0.05195% CI: [-12.6, 0]ANCOVA
Comparison: Comparison of capsaicin 8% and placebo for change from Baseline to Week 7.p-value: 0.01295% CI: [-14.4, -1.8]ANCOVA
Comparison: Comparison of capsaicin 8% and placebo for change from Baseline to Week 8.p-value: 0.02695% CI: [-13.5, -0.8]ANCOVA
Comparison: Comparison of capsaicin 8% and placebo for change from Baseline to Week 9.p-value: 0.03295% CI: [-13.2, -0.6]ANCOVA
Comparison: Comparison of capsaicin 8% and placebo for change from Baseline to Week 10.p-value: 0.0295% CI: [-13.9, -1.2]ANCOVA
Comparison: Comparison of capsaicin 8% and placebo for change from Baseline to Week 11.p-value: 0.02295% CI: [-13.7, -1.1]ANCOVA
Comparison: Comparison of capsaicin 8% and placebo for change from Baseline to Week 12.p-value: 0.00595% CI: [-15.3, -2.7]ANCOVA