title: 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.
abstract: BACKGROUND
  This 52-week study evaluated the long-term safety and tolerability of capsaicin 8% w/w (179 mg) patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy (PDPN).
  
  
  METHODS
  Phase 3, multinational, open-label, randomised, controlled, 52-week safety study, conducted in Europe. Patients were randomised to capsaicin 8% patch repeat treatment (30 or 60 min; 1-7 treatments with ≥ 8-week intervals) to painful areas of the feet plus SOC, or SOC alone. The primary objective was the safety of capsaicin 8% patch repeat treatment (30 min and 60 min applications) plus SOC versus SOC alone over 52 weeks, assessed by changes in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) total score from baseline to end of study (EOS). Secondary safety endpoints included Utah Early Neuropathy Scale (UENS) assessments and standardised testing of sensory perception and reflex function.
  
  
  RESULTS
  Overall, 468 patients were randomised (30 min plus SOC, n = 156; 60 min plus SOC, n = 157; SOC alone, n = 155). By EoS, mean changes in Norfolk QOL-DN total score from baseline [estimated mean difference versus SOC alone; 90% CI for difference] were: 30 min plus SOC, -27.6% [-20.9; -31.7, -10.1]; 60 min plus SOC, -32.8% [-26.1; -36.8, -15.4]; SOC alone, -6.7%. Mean changes [difference versus SOC alone] in UENS total score by EoS versus baseline were: 30 min plus SOC, -2.1 [-0.9; -1.8, 0.1]; 60 min plus SOC, -3.0 [-1.7; -2.7, -0.8]; SOC alone, -1.2. No detrimental deterioration was observed in any of the Norfolk or UENS subscales by EoS with capsaicin. Also, no worsening in sensory perception testing of sharp, warm, cold and vibration stimuli was found with capsaicin by EoS. Capsaicin treatment was well tolerated and the most frequent treatment-emergent adverse events were application site pain (30 min, 28.2%; 60 min, 29.3%), burning sensation (30 min, 9.0%; 60 min, 9.6%) and application site erythema (30 min, 7.7%; 60 min, 8.9%).
  
  
  CONCLUSIONS
  In patients with PDPN, capsaicin 8% patch repeat treatment plus SOC over 52 weeks was well tolerated with no negative functional or neurological effects compared with SOC alone.
  
  
  BACKGROUND
  ClinicalTrials.gov registration: NCT01478607 . Date of registration November 21, 2011; retrospectively registered.
authors.affiliation: Eastern Virginia Medical School, Strelitz Diabetes Center, 855 W Brambleton Avenue, Room 2018, Norfolk, VA, 23510, USA. vinikai@evms.edu.
authors.forename: Aaron I
authors.initials: AI
authors.lastname: Vinik
authors.affiliation: Hôpital Hôtel Dieu, Paris Descartes University, Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Perrot
authors.affiliation: Eastern Virginia Medical School, Strelitz Diabetes Center, 855 W Brambleton Avenue, Room 2018, Norfolk, VA, 23510, USA.
authors.forename: Etta J
authors.initials: EJ
authors.lastname: Vinik
authors.affiliation: Vestra Clinics - Dedicated Research Clinics, Rychnov nad Kneznou, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Pazdera
authors.affiliation: Astellas Pharma Europe B. V, Leiden, The Netherlands.
authors.forename: Hélène
authors.initials: H
authors.lastname: Jacobs
authors.affiliation: Astellas Pharma Europe B. V, Leiden, The Netherlands.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Stoker
authors.affiliation: Astellas Pharma Europe B. V, Leiden, The Netherlands.|INC Research, Camberley, UK.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Long
authors.affiliation: Astellas Pharma Europe B. V, Leiden, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Snijder
authors.affiliation: Astellas Pharma Europe B. V, Leiden, The Netherlands.
authors.forename: Marjolijne
authors.initials: M
authors.lastname: van der Stoep
authors.affiliation: Hospital Rio Hortega, Valladolid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Ortega
authors.affiliation: Analgesic Solutions, Natick, MA, USA.|Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Katz
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D002211:Capsaicin / Q000008:administration & dosage / Q000009:adverse effects*; D003929:Diabetic Neuropathies / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D017063:Outcome Assessment, Health Care; D018689:Sensory System Agents / Q000008:administration & dosage / Q000009:adverse effects*; D059039:Standard of Care
chemical_list: D018689:Sensory System Agents; D002211:Capsaicin
keywords: Capsaicin 8% patch; Norfolk QOL-DN; Painful diabetic peripheral neuropathy; TPRV1; UENS