Clinical trial NCT01533428: 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)
Official title: A Phase III, Double-blind, Randomized, Placebo-controlled, Multicenter Study Evaluating the Efficacy and Safety of QUTENZA® in Subjects With Painful Diabetic Peripheral Neuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetic Peripheral Neuropathy
Pain
Keywords: Painful Diabetic Peripheral Neuropathy,
Capsaicin 8% transdermal delivery system
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-02-15
Enrollment: 369
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Percent Change in the Average Daily Pain Score From Baseline to Between Weeks 2 and 8
timeFrame: Baseline to between Weeks 2 to 8
Secondary outcomes:
measure: Percent Change in the Average Daily Pain Score From Baseline to Between Weeks 2 and 12
timeFrame: Baseline to between Weeks 2 and 12
measure: Weekly Percent Change From Baseline in Average Daily Pain Score
timeFrame: Baseline to Weeks 2, 3, 4, 5, 6, 7, 8, 9,10, 11 and 12
measure: Weekly Average of Average Daily Pain at Baseline and Every Week After Baseline
timeFrame: Baseline and Weeks 2, 4, 8 and 12
measure: Percentage of Participants With 30% Reduction in Average Daily Pain Score.
timeFrame: Baseline, Weeks 2-8 and Weeks 2-12
measure: Percentage of Participants With 50% Reduction in Average Daily Pain Score.
timeFrame: Baseline, Weeks 2-8 and Weeks 2-12
measure: Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 2
timeFrame: Baseline to Week 2
measure: Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 8
timeFrame: Baseline to Week 8
measure: Overall Participant Status Assessed Using Patient Global Impression of Change (PGIC) Self-assessment Questionnaire in Week 12
timeFrame: Baseline to Week 12
measure: 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
timeFrame: Baseline to Weeks 2, 8 and 12
measure: Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Scale From Baseline to Weeks 2, 8 and 12
timeFrame: Baseline to Weeks 2, 8 and 12
measure: Change in Hospital Anxiety and Depression Scale (HADS) Depression Scale From Baseline to Weeks 2, 8 and 12.
timeFrame: Baseline to Weeks 2, 8 and 12
measure: Treatment Satisfaction Assessment Based on Self-Assessment of Treatment (SAT II) Questionnaire at Baseline, Weeks 8 and 12
timeFrame: Baseline, Weeks 8 and 12
measure: Percent Change in Average Sleep Interference Score From Baseline to Between Weeks 2-8 and Weeks 2-12
timeFrame: Baseline, Weeks 2-8 and Weeks 2-12
measure: Tolerability of Patch Application Assessed by Dermal Assessment on Day 1, 15 Minutes and 60 Minutes After Patch Removal.
timeFrame: Day 1, 15 minutes and 60 minutes after patch removal
measure: Change From Pre-application in"Pain Now" Score
timeFrame: Pre-application and 15 minutes and 60 minutes after patch removal
measure: Number of Participants Who Used Rescue Pain Medication Days 1 Through 5
timeFrame: Days 1 - 5
measure: Safety Assessed Through Adverse Events (AE) and Serious Adverse Events (SAE), Vital Signs, and Laboratory Analyses From Baseline to Week 12
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Site: 125
state: Alabama
city: Fresno
country: United States
facility: Site: 131
state: California
city: Long Beach
country: United States
facility: Site: 123
state: California
city: Los Angeles
country: United States
facility: Site: 116
state: California
city: Orange
country: United States
facility: Site: 112
state: California
city: Walnut Creek
country: United States
facility: Site: 130
state: California
city: Milford
country: United States
facility: Site: 113
state: Connecticut
city: New London
country: United States
facility: Site: 119
state: Connecticut
city: Boynton Beach
country: United States
facility: Site: 117
state: Florida
city: Bradenton
country: United States
facility: Site: 124
state: Florida
city: Clearwater
country: United States
facility: Site: 107
state: Florida
city: Jupiter
country: United States
facility: Site: 120
state: Florida
city: Orlando
country: United States
facility: Site: 108
state: Florida
city: Oviedo
country: United States
facility: Site: 132
state: Florida
city: St. Petersburg
country: United States
facility: Site: 127
state: Florida
city: Tampa
country: United States
facility: Site: 122
state: Florida
city: Honolulu
country: United States
facility: Site: 133
state: Hawaii
city: New Bedford
country: United States
facility: Site: 126
state: Massachusetts
city: Ann Arbor
country: United States
facility: Site: 115
state: Michigan
city: Hazelwood
country: United States
facility: Site: 128
state: Missouri
city: New York
country: United States
facility: Site:111
state: New York
city: Winston-Salem
country: United States
facility: Site: 110
state: North Carolina
city: Kettering
country: United States
facility: Site: 121
state: Ohio
city: Dallas
country: United States
facility: Site:106
state: Texas
city: Houston
country: United States
facility: Site: 118
state: Texas
city: Houston
country: United States
facility: Site: 114
state: Texas
city: Lubbock
country: United States
facility: Site: 103
state: Texas
city: San Antonio
country: United States
facility: Site: 105
state: Texas
city: San Antonio
country: United States
facility: Site: 102
state: Texas
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Clinical Study Manager
role: STUDY_CHAIR
References:
citation: 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.