title: Comparable efficacy and superior gastrointestinal tolerability (nausea, vomiting, constipation) of tapentadol compared with oxycodone hydrochloride.
abstract: BACKGROUND
  Two randomized, double-blind, placebo-controlled studies in acute and chronic pain treatment, powered to assess noninferiority of the efficacy of tapentadol immediate release (IR) (50 mg, 75 mg) versus oxycodone hydrochloride (HCl) IR (10 mg), established comparable efficacy of tapentadol IR with oxycodone HCl IR, and suggested tapentadol IR's improved gastrointestinal tolerability. The impact of these equianalgesic doses of tapentadol and oxycodone HCl on bowel function and gastrointestinal tolerability was then directly assessed in the current study, using a validated bowel function diary to comprehensively assess opioid-induced constipation symptoms and outcomes.
  
  
  METHODS
  In this double-blind study, patients with end-stage joint disease were randomized to tapentadol IR (50 mg or 75 mg), oxycodone HCl IR 10 mg, or placebo. Treatment with IR formulations (14 days) was followed by treatment (28 days) with extended-release (ER) formulations of active drugs (or placebo).
  
  
  RESULTS
  Oxycodone HCl IR treatment significantly decreased (P<0.001) mean (SD) number of spontaneous bowel movements over the 14-day period (average per week: [6.7 (5.44)] versus tapentadol IR 50 mg [9.0 (4.04)], tapentadol IR 75 mg [8.6 (4.65)], and placebo [9.9 (5.16)]) (primary measure), confirming the tolerability findings of the earlier studies. Additionally, incidences of nausea and vomiting were significantly lower over the 14-day period (nominal P<0.001) for tapentadol IR 50 and 75 mg, versus oxycodone HCl IR 10 mg. Results with ER formulations of tapentadol and oxycodone HCl over a longer treatment period were consistent with those of IR formulations.
  
  
  CONCLUSIONS
  Tapentadol IR (50 mg, 75 mg) consistently demonstrated superior gastrointestinal tolerability, including for the most commonly reported events, such as nausea, vomiting, and constipation at doses that provide comparable efficacy with oxycodone HCl IR 10 mg. These findings validate and extend the tolerability findings of the two earlier studies that established comparable efficacy of these tapentadol and oxycodone HCl doses.
authors.affiliation: Neuroscience, Johnson & Johnson Pharmaceutical Research & Development, Titusville, New Jersey 08560, USA. metropol@its.jnj.com
authors.forename: Mila
authors.initials: M
authors.lastname: Etropolski
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kelly
authors.forename: Akiko
authors.initials: A
authors.lastname: Okamoto
authors.forename: Christine
authors.initials: C
authors.lastname: Rauschkolb
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D002908:Chronic Disease; D003248:Constipation / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007592:Joint Diseases / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010636:Phenols / Q000008:administration & dosage* / Q000009:adverse effects*; D000077432:Tapentadol; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000701:Analgesics, Opioid; D010636:Phenols; D010098:Oxycodone; D000077432:Tapentadol