title: Safety and tolerability of tapentadol extended release in moderate to severe chronic osteoarthritis or low back pain management: pooled analysis of randomized controlled trials.
abstract: BACKGROUND
  This analysis of pooled data from four randomized, controlled-dose adjustment, phase 3 studies (three 15-week, double-blind, placebo- and active-controlled studies and a 1-year, open-label, active-controlled safety study) in patients with chronic osteoarthritis hip or knee pain or low back pain evaluated the safety and tolerability of tapentadol extended release (ER) for the management of moderate to severe, chronic pain.
  
  
  METHODS
  In the three 15-week studies, patients were randomized (1:1:1) to twice-daily (bid) doses of placebo, tapentadol ER (100-250 mg), or oxycodone hydrochloride (HCl) controlled release (CR; 20-50 mg). In the 1-year safety study, patients were randomized (4:1) to tapentadol ER (100-250 mg bid) or oxycodone HCl CR (20-50 mg bid). Adverse events (AEs) and discontinuations were recorded in each study; pooled results were analyzed by treatment group.
  
  
  RESULTS
  In the placebo (n = 993), tapentadol ER (n = 1,874), and oxycodone CR (n = 1,224) groups, respectively, 40.7%, 48.4%, and 62.3% of patients discontinued treatment prematurely and 58.7%, 79.0%, and 86.6% of patients experienced ≥ 1 treatment-emergent AE (TEAE). Incidences of gastrointestinal TEAEs in the placebo, tapentadol ER, and oxycodone CR groups, respectively, were 26.6%, 47.3%, and 65.4%; incidences of nervous system TEAEs were 22.5%, 42.6%, and 45.1%, respectively. Moderate or severe gastrointestinal TEAEs were reported for 10.9% of patients who received placebo, 25.3% of patients who received tapentadol ER, and 42.3% of patients who received oxycodone CR, and moderate or severe nervous system TEAEs were reported for 10.6%, 22.1%, and 25.2% of patients, respectively. In the placebo, tapentadol ER, and oxycodone CR groups, respectively, incidences of gastrointestinal TEAEs leading to study discontinuation were 2.1%, 8.3%, and 24.1%; incidences of nervous system TEAEs leading to discontinuation were 1.4%, 7.9%, and 16.3%, respectively.
  
  
  CONCLUSIONS
  Results from this large patient population showed that tapentadol ER (100-250 mg bid) had improved gastrointestinal tolerability compared with oxycodone CR, based on the overall incidence of gastrointestinal TEAEs, the incidence of moderate or severe gastrointestinal TEAEs, and the incidence of gastrointestinal TEAEs leading to discontinuation.
authors.affiliation: Janssen Research & Development, LLC, 1125 Trenton Harbourton Rd, Titusville, NJ, 08560, USA, MEtropol@its.jnj.com.
authors.forename: Mila
authors.initials: M
authors.lastname: Etropolski
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kuperwasser
authors.forename: Maren
authors.initials: M
authors.lastname: Flügel
authors.forename: Thomas
authors.initials: T
authors.lastname: Häufel
authors.forename: Bernd
authors.initials: B
authors.lastname: Lange
authors.forename: Christine
authors.initials: C
authors.lastname: Rauschkolb
authors.forename: Frank
authors.initials: F
authors.lastname: Laschewski
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects; D059350:Chronic Pain / Q000175:diagnosis / Q000188:drug therapy; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D017116:Low Back Pain / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000175:diagnosis / Q000188:drug therapy; D020370:Osteoarthritis, Knee / Q000175:diagnosis / Q000188:drug therapy; D010098:Oxycodone / Q000008:administration & dosage / Q000009:adverse effects; D059408:Pain Management / Q000379:methods; D010147:Pain Measurement; D010636:Phenols / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D017450:Receptors, Opioid, mu / Q000819:agonists; D000077432:Tapentadol; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D003692:Delayed-Action Preparations; D010636:Phenols; D017450:Receptors, Opioid, mu; D010098:Oxycodone; D000077432:Tapentadol