title: Novel design for a phase IIa placebo-controlled, double-blind randomized withdrawal study to evaluate the safety and efficacy of CNV1014802 in patients with trigeminal neuralgia.
abstract: BACKGROUND
  Trigeminal neuralgia (TN) is a rare severe unilateral facial pain condition. Current guidelines in trigeminal neuralgia management recommend sodium channel blockers--carbamazepine or oxcarbazepine--as the first-line treatment. However, the currently available drugs are often associated with poor tolerability resulting in sub-optimal pain control. CNV1014802 is a novel sodium channel blocker that is being assessed in the treatment of trigeminal neuralgia. Due to the severity of the condition, it is not ethical to conduct a traditional placebo-controlled randomized controlled trial. It is also difficult to use an active control such as carbamazepine, the current gold standard, because of its complex pharmacology and potential for drug interactions.
  
  
  METHODS
  The trial uses a randomized withdrawal design to assess efficacy in this rare condition. There is a 21-day open-label phase followed by a randomized 28-day placebo-controlled phase for responders. Thirty patients will be randomized. The primary outcome measure will be pain relief, but secondary measures of quality of life will be of significant importance given the effect of this condition on activities of daily living. Safety and adverse event endpoints are described.
  
  
  CONCLUSIONS
  There have been very few well-controlled, randomized, placebo-controlled studies in trigeminal neuralgia, and the majority of drugs have had other primary uses. Due to the severity of the pain, minimizing the time a patient is administered placebo was a key factor in designing this study. This study will not only provide data on the efficacy of CNV1014802 in trigeminal neuralgia, but will also provide information on the effectiveness and acceptability of a novel trial design in trigeminal neuralgia.
  
  
  BACKGROUND
  Trial number NCT01540630.
authors.affiliation: Facial pain unit, Division of Diagnostic, Surgical and Medical Sciences, Eastman Dental Hospital, UCLH NHS Foundation Trust/University College London, 256 Gray's Inn Road, WC1X 8LD, London, UK. j.zakrzewska@ucl.ac.uk.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Zakrzewska
authors.forename: Joanne
authors.initials: J
authors.lastname: Palmer
authors.forename: Dominik A
authors.initials: DA
authors.lastname: Ettlin
authors.forename: Mark
authors.initials: M
authors.lastname: Obermann
authors.forename: Gerard M P
authors.initials: GM
authors.lastname: Giblin
authors.forename: Valerie
authors.initials: V
authors.lastname: Morisset
authors.forename: Simon
authors.initials: S
authors.lastname: Tate
authors.forename: Kevin
authors.initials: K
authors.lastname: Gunn
mesh_terms: D004311:Double-Blind Method; D006801:Humans; D017063:Outcome Assessment, Health Care; D010647:Phenyl Ethers / Q000009:adverse effects / Q000627:therapeutic use*; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012107:Research Design; D026941:Sodium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D014277:Trigeminal Neuralgia / Q000188:drug therapy*; D028761:Withholding Treatment
chemical_list: D010647:Phenyl Ethers; D026941:Sodium Channel Blockers; D011392:Proline; C000592131:vixotrigine