title: Dextromethorphan and quinidine in adult patients with uncontrolled painful diabetic peripheral neuropathy: a 29-day, multicenter, open-label, dose-escalation study.
abstract: BACKGROUND
  Pain associated with diabetic peripheral neuropathy (DPN) has a substantial negative impact on patients' quality of life.
  
  
  OBJECTIVE
  The primary objective of this study was to evaluate the tolerability of capsules containing dextromethorphan (DM) and quinidine (Q) in patients with painful DPN. A secondary objective was to perform a preliminary assessment of the efficacy of DM/Q in this patient population.
  
  
  METHODS
  This was a multicenter, open-label, dose-escalation study. Eligible patients were aged between 18 and 80 years, had a confirmed diagnosis of diabetes with acceptable glycemic control, had been receiving established diabetic therapy for at least 3 months, and had a clinical diagnosis of distal symmetric sensory neuropathy with daily DPN-associated pain for the previous 3 months. On study entry, patient-rated diabetic pain had to be moderate or greater. Patients who met the inclusion criteria underwent a 2-week washout period during which all analgesics were discontinued, followed by 29 days of treatment with capsules containing DM 30 mg and Q 30 mg (DM30/Q30), beginning with 1 capsule/d and escalating at approximately 1-week intervals, as tolerated, to a maximum dose of 4 capsules/d (DM120/Q120). Tolerability was assessed based on adverse events and changes in clinical and laboratory parameters and nerve conduction velocity. Preliminary efficacy assessments included changes from baseline in scores on the pain intensity rating scale (PIRS), pain relief rating scale (PRRS), peripheral neuropathy quality-of-life instrument, and patients' diary assessments of sleep, present pain intensity, pain, and activity.
  
  
  RESULTS
  The study included 36 men and women (mean age, 58 years; mean body mass index, 32.8 kg/m(2)). Of the 33 subjects who completed the study, 23 (69.7%) did so at the highest permitted dose (DM120/Q120). The most commonly reported adverse events (occurring in > or =5% of subjects) were nausea (27.8%), dizziness (25.0%), and headache (25.0%). Three patients experienced 5 serious adverse events, only 1 of which was considered possibly related to study drug. The most commonly occurring laboratory abnormalities (involving glycosylated hemoglobin, serum glucose, triglycerides, and cholesterol) were considered typical of a population with diabetes. Improvements from baseline in scores on the PIRS, PRRS, and other exploratory efficacy measures were noted (P < 0.001).
  
  
  CONCLUSIONS
  The results of this open-label study indicated that the combination of DMIQ (dose range, DM30/Q30-DM120/Q120) was well tolerated in patients with pain associated with DPN. Based on the preliminary efficacy results, a randomized, controlled, double-blind trial is warranted to assess the tolerability and efficacy of this combination in patients with DPN.
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, Illinois 60637, USA. r-thisted@uchicago.edu
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Thisted
authors.forename: Leslie
authors.initials: L
authors.lastname: Klaff
authors.forename: Sherwyn L
authors.initials: SL
authors.lastname: Schwartz
authors.forename: James P
authors.initials: JP
authors.lastname: Wymer
authors.forename: Neil W
authors.initials: NW
authors.lastname: Culligan
authors.forename: Gary
authors.initials: G
authors.lastname: Gerard
authors.forename: Laura E
authors.initials: LE
authors.lastname: Pope
authors.forename: James E
authors.initials: JE
authors.lastname: Berg
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D002853:Chromatography, Liquid; D003915:Dextromethorphan / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010146:Pain / Q000178:diet therapy / Q000209:etiology; D011802:Quinidine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D003915:Dextromethorphan; D011802:Quinidine