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) (STEP)

A Phase III, Double-blind, Randomized, Placebo-controlled, Multicenter Study Evaluating the Efficacy and Safety of QUTENZA® in Subjects With Painful Diabetic Peripheral Neuropathy

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.

Study Overview

• Status: Completed
• Conditions: Pain; Diabetic Peripheral Neuropathy
• Intervention / Treatment: Drug: Capsaicin 8%; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 369
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Site: 125
  • California
    • Fresno, California, United States, 93720
      • Site: 131
    • Long Beach, California, United States, 90806
      • Site: 123
    • Los Angeles, California, United States, 90033
      • Site: 116
    • Orange, California, United States, 92868
      • Site: 112
    • Walnut Creek, California, United States, 94597
      • Site: 130
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Site: 113
    • New London, Connecticut, United States, 06320
      • Site: 119
  • Florida
    • Boynton Beach, Florida, United States, 33435
      • Site: 117
    • Bradenton, Florida, United States, 34205
      • Site: 124
    • Clearwater, Florida, United States, 33765
      • Site: 107
    • Jupiter, Florida, United States, 33458
      • Site: 120
    • Orlando, Florida, United States, 32806
      • Site: 108
    • Oviedo, Florida, United States, 32765
      • Site: 132
    • St. Petersburg, Florida, United States, 33709
      • Site: 127
    • Tampa, Florida, United States, 33606
      • Site: 122
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Site: 133
  • Massachusetts
    • New Bedford, Massachusetts, United States, 02740
      • Site: 126
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Site: 115
  • Missouri
    • Hazelwood, Missouri, United States, 63042
      • Site: 128
  • New York
    • New York, New York, United States, 10029
      • Site:111
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Site: 110
  • Ohio
    • Kettering, Ohio, United States, 45429
      • Site: 121
  • Texas
    • Dallas, Texas, United States, 75230
      • Site:106
    • Houston, Texas, United States, 77030
      • Site: 118
    • Houston, Texas, United States, 77098
      • Site: 114
    • Lubbock, Texas, United States, 79410
      • Site: 103
    • San Antonio, Texas, United States, 78228
      • Site: 105
    • San Antonio, Texas, United States, 78229
      • Site: 102

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: Qutenza
Placebo Comparator: Placebo; Placebo patch was applied for 30 minutes to the painful area(s) on Day 1	Drug: Placebo; Placebo Patch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline to between Weeks 2 to 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline to between Weeks 2 and 12
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).	Baseline to Weeks 2, 3, 4, 5, 6, 7, 8, 9,10, 11 and 12
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).	Baseline and Weeks 2, 4, 8 and 12
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).	Baseline, Weeks 2-8 and Weeks 2-12
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).	Baseline, Weeks 2-8 and Weeks 2-12
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	Baseline to Week 2
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	Baseline to Week 8
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	Baseline to 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	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).	Baseline to Weeks 2, 8 and 12
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.	Baseline to Weeks 2, 8 and 12
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.	Baseline to Weeks 2, 8 and 12
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?"	Baseline, Weeks 8 and 12
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.	Baseline, 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.	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.	Day 1, 15 minutes and 60 minutes after patch removal
Change From Pre-application in"Pain Now" Score	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.	Pre-application and 15 minutes and 60 minutes after patch removal
Number of Participants Who Used Rescue Pain Medication Days 1 Through 5	Summarized number of participants who used Rescue Pain Medications for Pain	Days 1 - 5
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	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

General Publications

• Simpson DM, Robinson-Papp J, Van J, Stoker M, Jacobs H, Snijder RJ, Schregardus DS, Long SK, Lambourg B, Katz N. Capsaicin 8% Patch in Painful Diabetic Peripheral Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Study. J Pain. 2017 Jan;18(1):42-53. doi: 10.1016/j.jpain.2016.09.008. Epub 2016 Oct 13.

Helpful Links

• Link to results on Astellas Clinical Study Results Web site

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: February 12, 2012
• First Submitted That Met QC Criteria: February 14, 2012
• First Posted (Estimate): February 15, 2012

Study Record Updates

• Last Update Posted (Estimate): November 4, 2015
• Last Update Submitted That Met QC Criteria: October 12, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Painful Diabetic Peripheral Neuropathy,; Capsaicin 8% transdermal delivery system
• Additional Relevant MeSH Terms: Nervous System Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Diabetic Neuropathies; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Dermatologic Agents; Antipruritics; Capsaicin
• Other Study ID Numbers: E05-CL-3004