title: Challenges of correlating pH change with relief of clinical symptoms in gastro esophageal reflux disease: a phase III, randomized study of Zegerid versus Losec.
abstract: BACKGROUND
  Zegerid (on demand immediate-release omeprazole and sodium bicarbonate combination therapy) has demonstrated earlier absorption and more rapid pH change compared with Losec (standard enteric coated omeprazole), suggesting more rapid clinical relief of heartburn. This Phase III, multicenter, double-blind, double-dummy, randomized study assessed the clinical superiority of Zegerid versus Losec for rapid relief of heartburn associated with gastro-esophageal reflux disease (GERD).
  
  
  METHODS
  Patients with a history of frequent (2 3 days/week) uncomplicated GERD, were randomized to receive Zegerid (20 mg) or Losec (20 mg) with corresponding placebo. Study medication was self-administered on the first episode of heartburn, and could be taken for up to 3 days within a 14 day study period. Heartburn severity was self assessed up to 180 minutes post dose (9 point Likert scale). Primary endpoint was median time to sustained response (≥3 point reduction in heartburn severity for ≥45 minutes).
  
  
  RESULTS
  Of patients randomized to Zegerid (N=122) or Losec (N=117), 228/239 had recorded ≥1 evaluable heartburn episodes and were included in the modified intent-to-treat population. No significant between-group differences were observed for median time to sustained response (60.0 vs. 52.2 minutes, Zegerid [N=117] and Losec [N=111], respectively), sustained partial response (both, 37.5 minutes) and sustained total relief (both, 105 minutes). Significantly more patients treated with Zegerid reached sustained total relief within 0-30 minutes post dose in all analysis sets (p<0.05). Both treatments were well tolerated and did not raise any safety concerns.
  
  
  CONCLUSIONS
  Superiority of Zegerid over Losec for rapid heartburn relief was not demonstrated; both treatments were equally effective however the rapid onset of action of Losec was unexpected. Factors, including aspects of study design may have contributed to this. This study supports previously reported difficulty in correlating intra-gastric pH change with clinical effect in GERD therapy, highlighting the significance of several technical considerations for studies of this type.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01493089.
authors.affiliation: Norgine Ltd, Uxbridge, United Kingdom.
authors.forename: Dave
authors.initials: D
authors.lastname: Walker
authors.affiliation: Norgine Ltd, Uxbridge, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Ng Kwet Shing
authors.affiliation: Norgine Ltd, Uxbridge, United Kingdom.
authors.forename: Deborah
authors.initials: D
authors.lastname: Jones
authors.affiliation: Medical and Safety Services, ICON Clinical Research, Eastleigh, United Kingdom.
authors.forename: Hans-Jurgen
authors.initials: HJ
authors.lastname: Gruss
authors.affiliation: Department of Gastroenterology, Institute of Oncology and Medical Centre for Postgraduate Education, Warsaw, Poland.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Reguła
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000378:metabolism; D006356:Heartburn / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000494:pharmacology / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017693:Sodium Bicarbonate / Q000494:pharmacology / Q000627:therapeutic use*; D013270:Stomach / Q000187:drug effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D054328:Proton Pump Inhibitors; C494109:omeprazole, sodium bicarbonate drug combination; D017693:Sodium Bicarbonate; D009853:Omeprazole