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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01533428
First received: February 12, 2012
Last updated: March 3, 2015
Last verified: March 2015
  Purpose

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 Intervention Phase
Diabetic Peripheral Neuropathy
Pain
Drug: Capsaicin 8%
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Percent Change in the Average Daily Pain Score From Baseline to Between Weeks 2 and 8 [ Time Frame: Baseline to between Weeks 2 to 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to between Weeks 2 and 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Weeks 2, 3, 4, 5, 6, 7, 8, 9,10, 11 and 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline, Weeks 2-8 and Weeks 2-12 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline, Weeks 2-8 and Weeks 2-12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 2 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Weeks 2, 8 and 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Weeks 2, 8 and 12 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline to Weeks 2, 8 and 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Weeks 8 and 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Weeks 2-8 and Weeks 2-12 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Day 1, 15 minutes and 60 minutes after patch removal ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pre-application and 15 minutes and 60 minutes after patch removal ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1 - 5 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: Yes ]
    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


Enrollment: 369
Study Start Date: February 2012
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Qutenza
Placebo Comparator: Placebo
Placebo patch was applied for 30 minutes to the painful area(s) on Day 1
Drug: Placebo
Placebo Patch
Other Name: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01533428

  Show 29 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Chair: Clinical Study Manager Astellas Pharma Europe B.V.
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01533428     History of Changes
Other Study ID Numbers: E05-CL-3004
Study First Received: February 12, 2012
Results First Received: February 6, 2015
Last Updated: March 3, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
Painful Diabetic Peripheral Neuropathy,
Capsaicin 8% transdermal delivery system

Additional relevant MeSH terms:
Diabetic Neuropathies
Peripheral Nervous System Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Nervous System Diseases
Neuromuscular Diseases
Capsaicin
Antipruritics
Dermatologic Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 28, 2015