A Study to Evaluate the Long-term Safety of Repeated QUTENZA Administration for Treatment of Pain Caused by Nerve Damage in Diabetic Patients (PACE)

A Randomized, Controlled, Long-term Safety Study Evaluating the Effect of Repeated Applications of QUTENZATM Plus Standard of Care Versus Standard of Care Alone in Subjects With Painful Diabetic Peripheral Neuropathy

The purpose of the study is to assess the safety of repeated applications of QUTENZA in reducing pain intensity in subjects who have peripheral neuropathic pain due to diabetes.

Study Overview

• Status: Completed
• Conditions: Painful Diabetic Peripheral Neuropathy (PDPN)
• Intervention / Treatment: Drug: QUTENZA

Detailed Description

Patients will be divided into 3 groups of approximately equal size. In the first group, patients will receive a QUTENZA patch applied for 30 minutes to the feet; in the second group, patients will receive a QUTENZA patch applied for 60 minutes to the feet. In both these groups patients will also continue to receive their normal treatment (Standard of Care (SOC)) for their peripheral neuropathic pain (PNP) and may receive further QUTENZA patch applications in the same way during the study. The third group will not receive a QUTENZA patch but will continue to receive their normal treatment for their neuropathic pain (SOC). Subjects will be involved in the study for up to 15 months and will have to visit the clinic at least 9 times.

• Study Type: Interventional
• Enrollment (Actual): 468
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bonheiden, Belgium, 2820
    • Site: 601
• Czech Republic
  • Beroun, Czech Republic, 26601
    • Site: 903
  • Brno, Czech Republic, 60200
    • Site: 910
  • Chocen, Czech Republic, 56501
    • Site: 908
  • Litomerice, Czech Republic, 41201
    • Site: 911
  • Ostrava, Czech Republic, 71000
    • Site: 906
  • Policka, Czech Republic, 57201
    • Site: 904
  • Praha 4, Czech Republic, 14000
    • Site: 901
  • Prerov, Czech Republic, 75003
    • Site: 902
  • Rychnov nad Kneznou, Czech Republic, 51601
    • Site: 909
• France
  • Bron, France, 69677
    • Site: 207
  • Paris, France, 75004
    • Site: 202
  • Pierre Benite, France, 69495
    • Site: 201
  • Toulouse, France, 31059
    • Site: 206
• Germany
  • Chiemsee, Germany, 83209
    • Site: 508
  • Dresden, Germany, 1307
    • Site: 502
  • Falkensee, Germany, 14612
    • Site: 501
  • Frankfurt, Germany, 60311
    • Site: 514
  • Hamburg, Germany, 22177
    • Site: 507
  • Koln, Germany, 50937
    • Site: 509
  • Leipzig, Germany, 04109
    • Site: 505
  • Muenster, Germany, 48145
    • Site: 506
  • Wangen, Germany, 88239
    • Site: 512
• Italy
  • Milano, Italy, 20162
    • Site: 404
  • Roma, Italy, 00133
    • Site: 401
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Site: 651
• Poland
  • Bialystok, Poland, 15435
    • Site: 965
  • Bydgoszcz, Poland, 85822
    • Site: 961
  • Elblag, Poland, 82300
    • Site: 957
  • Gdynia, Poland, 81049
    • Site: 958
  • Katowice, Poland, 40954
    • Site: 954
  • Krakow, Poland, 31530
    • Site: 964
  • Lodz, Poland, 90153
    • Site: 951
  • Lubin, Poland, 59300
    • Site: 966
  • Poznan, Poland, 61655
    • Site: 953
  • Torun, Poland, 87100
    • Site: 959
  • Warszawa, Poland, 1868
    • Site: 960
• Russian Federation
  • Kemerovo, Russian Federation, 150062
    • Site: 714
  • Samara, Russian Federation, 79117778999
    • Site: 708
  • Saratov, Russian Federation, 79117120826
    • Site: 709
  • St. Petersburg, Russian Federation, 191015
    • Site: 703
  • St. Petersburg, Russian Federation, 194358
    • Site: 716
  • St. Petersburg, Russian Federation, 79117120826
    • Site: 704
  • St. Petersburg, Russian Federation, 79117778999
    • Site: 706
  • Tomsk, Russian Federation, 79117778999
    • Site: 713
  • Yaroslavl, Russian Federation, 79117778999
    • Site: 711
• Spain
  • Valencia, Spain, 46010
    • Site: 303
  • Valencia, Spain, 46014
    • Site: 304
  • Valladolid, Spain, 47012
    • Site: 305
• Ukraine
  • Chernihiv, Ukraine, 14034
    • Site: 808
  • Kharkiv, Ukraine, 61037
    • Site: 803
  • Kvuv, Ukraine, 79010
    • Site: 812
  • Kyiv, Ukraine, 2091
    • Site: 805
  • Kyiv, Ukraine, 4053
    • Site: 807
  • Kyiv, Ukraine, 4114
    • Site: 806
  • Lviv, Ukraine, 79010
    • Site: 810
  • Mykolayiv, Ukraine, 54003
    • Site: 802
  • Odesa, Ukraine, 65009
    • Site: 801
  • Vinnitsa, Ukraine, 21010
    • Site: 813
  • Zaporizhzhya, Ukraine, 69001
    • Site: 815
• United Kingdom
  • Chorley, United Kingdom, PR7 1PP
    • Site: 102
  • Liverpool, United Kingdom, L7 8XP
    • Site: 103
  • Poole, United Kingdom, BH15 2JB
    • Site: 104
  • Rugby, United Kingdom, CV22 5PX
    • Site: 101

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
• Stable glycemic control for at least 6 months 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 in the ankles or above
• Pain that could not be clearly differentiated from, or conditions that might interfere with, the assessment of PDPN
• Significant pain (moderate or above) of an etiology other than PDPN, that may interfere with judging PDPN-related pain
• Female subjects of childbearing potential must have a negative serum or urine pregnancy test at enrollment and must agree to maintain highly effective birth control during the study.
• Hypersensitivity to capsaicin (i.e., chili peppers or over-the-counter [OTC] capsaicin products), any QUTENZA excipients, Eutectic Mixture of Local Anesthetics( EMLA) ingredients or adhesives

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1. Qutenza 30 minutes + SOC	Drug: QUTENZA; A Qutenza (8% capsaicin) patch will be applied to identified painful areas for 30 minutes (Arm 1) or 60 minutes (Arm 2).; Other Names: Capsaisin
Experimental: 2. Qutenza 60 minutes + SOC	Drug: QUTENZA; A Qutenza (8% capsaicin) patch will be applied to identified painful areas for 30 minutes (Arm 1) or 60 minutes (Arm 2).; Other Names: Capsaisin
No Intervention: 3. SOC; Subjects randomized to this group will receive treatment optimized for them on an individual basis. The investigator will be free to provide whatever pharmacological or other treatment is considered optimal for management of the subject's pain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage change in health related quality of life (HRQOL) total score as assessed by the disease specific Norfolk scale	Baseline till endpoint (discontinuation or End of Study visit) (up to 64 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological function as assessed by the Utah Early Neuropathy Scale (UENS) and sensory testing	Physicians measuring neurological function will be blinded to treatment	Baseline till End of Study (up to 64 weeks)
Tolerability of patch application by dermal assessment		Screening till Last visit when QUTENZA patch is applied (up to 53 weeks)
Tolerability of patch application by "pain now" Numeric Pain Rating Scale (NPRS) scores after patch application	Assessed within 15 minutes and 60 minutes after patch removal.	Baseline till Last visit when QUTENZA patch is applied (up to 52 weeks)
Tolerability of patch application by rescue medication use		Days 1 through 5 after each patch application
Adverse Events and serious adverse Events		Screening visit through End of study visit (up to 65 weeks)
Vital Signs (heart rate and blood pressure)	In case of patch application to be performed within 15 minutes before topical anesthetic application and within 15 minutes after patch removal.	Screening visit through End of study visit (up to 65 weeks)
Laboratory Analyses	The tests performed at the screening visit will include Hematology: Red Blood Cell Count, White Blood Cell Count, Lymphocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Hemoglobin, Hematocrit and Platelets. Biochemistry: Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT), Alkaline Phosphatase, Sodium, Potassium, Blood Urea Nitrogen (BUN), Creatinine and Lipid profile. Subsequent HbA1c and lipid profile follow-up will be done at bi-monthly visits. The other tests will be performed if clinically indicated.	Screening visit through End of study visit (up to 65 weeks)
Intensity of neuropathic pain using "average pain" NPRS scores	Question 5 of Brief Pain Inventory-Diabetic Neuropathy (BPI-DN)	Screening visit through End of study visit (up to 65 weeks)
Brief Pain Inventory (BPI) pain severity index and pain interference index		Screening visit through End of study visit (up to 65 weeks)
Patient Global Impression of Change		After each patch re-application, from first patch re-application through End of Study visit (up to 56 weeks)
Generic HRQOL measured by European Quality of Life - 5 Dimensions (EQ-5D) questionnaire		After each patch application, from first patch application through End of Study (up to 64 weeks)
Treatment satisfaction using the Self-Assessment of Treatment (SAT) questionnaire at week 12/End Of Study visit		End of Study (up to 65 weeks)

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Senior Clinical Study Manager, Astellas Pharma Europe B.V.

Publications and helpful links

General Publications

• Vinik AI, Perrot S, Vinik EJ, Pazdera L, Jacobs H, Stoker M, Long SK, Snijder RJ, van der Stoep M, Ortega E, Katz N. Capsaicin 8% patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy: a randomised, 52-week, open-label, safety study. BMC Neurol. 2016 Dec 6;16(1):251. doi: 10.1186/s12883-016-0752-7.

Helpful Links

• Link to results on EudraCT
• Link to results on Astellas Clinical Study Results Web site

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: November 21, 2011
• First Submitted That Met QC Criteria: November 21, 2011
• First Posted (Estimate): November 23, 2011

Study Record Updates

• Last Update Posted (Estimate): October 14, 2015
• Last Update Submitted That Met QC Criteria: October 12, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Qutenza; Painful Diabetic Peripheral Neuropathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pain; Diabetic Neuropathies; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Dermatologic Agents; Antipruritics; Capsaicin
• Other Study ID Numbers: E05-CL-3002; 2009-016458-42 (EudraCT Number)