title: Comparison of Two Forms of Loperamide-Simeticone and a Probiotic Yeast (Saccharomyces boulardii) in the Treatment of Acute Diarrhoea in Adults: A Randomised Non-Inferiority Clinical Trial.
abstract: BACKGROUND
  Acute diarrhoea is a frequent health problem in both travellers and residents that has a social and economic impact. This study compared the efficacy and tolerability of two loperamide-simeticone formulations and a Saccharomyces boulardii capsule as symptomatic treatment.
  
  
  METHODS
  This was a prospective, randomised, single (investigator)-blind, three-arm, parallel group, non-inferiority clinical trial in adult subjects with acute diarrhoea at clinics in Mexico and India, with allocation to a loperamide-simeticone 2/125 mg caplet or chewable tablet (maximum eight in 48 h) or S. boulardii (250 mg twice daily for 5 days).
  
  
  METHODS
  The primary outcome measure was the number of unformed stools between 0 and 24 h following the initial dose of study medication (NUS 0-24). The secondary outcome measures were time to last unformed stool (TLUS), time to complete relief of diarrhoea (TCRD), time to complete relief of abdominal discomfort (TCRAD) and the subject's evaluation of treatment effectiveness. Follow-up endpoints at 7 days were feeling of complete wellness; stool passed since final study visit; and continued or recurrent diarrhoea.
  
  
  METHODS
  In this study, 415 subjects were randomised to either a loperamide-simeticone caplet (n = 139), loperamide-simeticone chewable tablet (n = 139) or S. boulardii capsule (n = 137) and were included in the intention-to-treat analysis.
  
  
  RESULTS
  With regards to mean NUS 0-24, the loperamide-simeticone caplet was non-inferior to loperamide-simeticone tablets (3.4 vs. 3.3; one-sided 97.5 % confidence interval ≤0.5), with both significantly lower than S. boulardii (4.3; p < 0.001). The loperamide-simeticone groups had a shorter median TLUS [14.9 and 14.0 vs. 28.5 h (loperamide-simeticone caplet and chewable tablet groups, respectively, vs. S. boulardii); p < 0.001], TCRD (26.0 and 26.0 vs. 45.8 h; p < 0.001) and TCRAD (12.2 and 12.0 vs. 23.9 h; p < 0.005) than S. boulardii. Treatment effectiveness for overall illness, diarrhoea and abdominal discomfort relief was greater (p < 0.001) in the loperamide-simeticone groups than with S. boulardii. At 7-day follow-up most subjects reported passing stool at least once since the final study visit (loperamide-simeticone caplet 94.1 %, loperamide-simeticone chewable tablet 94.8 %, S. boulardii 97.0 %), did not experience continued or recurrent diarrhoea [loperamide-simeticone caplet 3.7 % (p < 0.03 vs. S. boulardii), loperamide-simeticone chewable tablet 3.7 %, S. boulardii 5.7 %] and felt completely well [loperamide-simeticone caplet 96.3 % (p < 0.02 vs. S. boulardii), loperamide-simeticone chewable tablet 96.3 % (p < 0.02 vs. S. boulardii), S. boulardii 88.6 %]. All treatments were well-tolerated with few adverse events.
  
  
  CONCLUSIONS
  The loperamide-simeticone caplet was non-inferior to the original loperamide-simeticone chewable tablet formulation; both formulations can be expected to demonstrate similar clinical efficacy in the relief of symptoms of acute diarrhoea. Both loperamide-simeticone formulations were superior to the S. boulardii capsule in the primary and secondary endpoints.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT00807326.
authors.affiliation: Medical Affairs, Johnson & Johnson Ltd, Foundation Park, Roxborough Way, Maidenhead, SL6 3UG, UK. jcottre1@its.jnj.com.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Cottrell
authors.affiliation: Medical Affairs, Johnson & Johnson Ltd, Foundation Park, Roxborough Way, Maidenhead, SL6 3UG, UK.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Koenig
authors.affiliation: McNeil AB, PO Box 941, 251 09, Helsingborg, Sweden.
authors.forename: Roland
authors.initials: R
authors.lastname: Perfekt
authors.affiliation: Johnson & Johnson GmbH, Johnson & Johnson Platz 2 (Raiffeisenstraße 9), 41470, Neuss, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Hofmann
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D003967:Diarrhea / Q000188:drug therapy*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008139:Loperamide / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019936:Probiotics / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D012440:Saccharomyces; D012841:Simethicone / Q000009:adverse effects / Q000627:therapeutic use*; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D008139:Loperamide; D012841:Simethicone