title: Efficacy and tolerability studies evaluating a sleep aid and analgesic combination of naproxen sodium and diphenhydramine in the dental impaction pain model in subjects with induced transient insomnia.
abstract: OBJECTIVE
  The aim of this study was to evaluate the efficacy and tolerability of novel combination naproxen sodium (NS) and diphenhydramine (DPH) in subjects with postoperative dental pain along with transient insomnia induced by 5 h sleep phase advance. The present studies aimed to demonstrate the added benefit and optimal dosages of the combination product over individual ingredients alone in improving sleep and pain.
  
  
  METHODS
  Each of the two studies was a two-centre, randomised, double-blind and double-dummy trial. In the first study, subjects were randomised into one of the following treatment arms: NS 440 mg/DPH 50 mg, NS 220 mg/DPH 50 mg, NS 440 mg or DPH 50 mg. In the second study, subjects received either NS 440 mg/DPH 25 mg, NS 440 mg or DPH 50 mg. The co-primary end-points in both studies were wake time after sleep onset (WASO) and sleep latency (SL) measured by actigraphy. Other secondary sleep and pain end-points were also assessed.
  
  
  RESULTS
  The intent-to-treat population included 712 and 267 subjects from studies one and two, respectively. In the first study, only the NS 440 mg/DPH 50 mg combination showed significant improvements in both WASO vs. NS alone (-70.3 min p = 0.0002) and SL vs. DPH alone (25.50 and 41.50 min respectively, p < 0.0001). In the second study, the NS 440 mg/DPH 25 mg combination failed to show any significant improvements vs. either component alone.
  
  
  CONCLUSIONS
  Only the NS 440 mg/DPH 50 mg combination demonstrated improvement in both sleep latency vs. DPH 50 mg and sleep maintenance (WASO) vs. NS 440 mg. There were no serious or unexpected adverse events reported in either study.
  
  
  BACKGROUND
  NCT01280591 (study 1); NCT01495858 (study 2).
authors.affiliation: LLC, Palm Beach Gardens, FL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cooper
authors.affiliation: Bayer HealthCare Consumer Care, Whippany, NJ, USA.
authors.forename: I
authors.initials: I
authors.lastname: Laurora
authors.affiliation: Bayer HealthCare Consumer Care, Whippany, NJ, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Bayer HealthCare Consumer Care, Whippany, NJ, USA.
authors.forename: P
authors.initials: P
authors.lastname: Venkataraman
authors.affiliation: Bayer HealthCare Consumer Care, Whippany, NJ, USA.
authors.forename: R
authors.initials: R
authors.lastname: An
authors.affiliation: Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: T
authors.initials: T
authors.lastname: Roth
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D004155:Diphenhydramine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006993:Hypnotics and Sedatives; D008297:Male; D009288:Naproxen / Q000008:administration & dosage*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D017286:Polysomnography; D012890:Sleep / Q000502:physiology*; D000068776:Sleep Aids, Pharmaceutical / Q000008:administration & dosage*; D007319:Sleep Initiation and Maintenance Disorders / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D014081:Tooth Extraction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006993:Hypnotics and Sedatives; D000068776:Sleep Aids, Pharmaceutical; D009288:Naproxen; D004155:Diphenhydramine