title: Effect of food on the pharmacokinetics of canagliflozin/metformin (150/1,000 mg) immediate-release fixed-dose combination tablet in healthy participants.
abstract: OBJECTIVE
  To assess the effect of food on the pharmacokinetics (PK) of canagliflozin and metformin following administration of a canagliflozin/metformin (150/1,000 mg) immediate-release (IR) fixed-dose combination (FDC) tablet.
  
  
  METHODS
  A randomized, open-label, singlecenter, single-dose, 2-period, 2-sequence crossover study was conducted in healthy participants. Participants were randomized to 2 sequences of fasted and fed (or vice versa) administration of one 150/1,000 mg canagliflozin/metformin IR FDC, with 10-14 day washout between treatments PK parameters (AUC, Cmax, tmax, t1/2) were assessed for canagliflozin and metformin. Safety was evaluated.
  
  
  RESULTS
  When comparing the IR FDC tablet administered with and without food, PK parameters of canagliflozin were bioequivalent as the 90% confidence intervals (CIs) for log-transformed AUClast, AUCâ, and Cmax were within the bioequivalence limits of 80-125%. For metformin, overall exposure was similar under fed and fasted conditions as geometric mean ratios for AUC and associated 90% CI were contained within the bioequivalence limits, but geometric mean Cmax decreased by 16% in the fed compared to fasted state. Both treatments were well tolerated with similar adverse events and most common were gastrointestinal events, generally attributed to metformin.
  
  
  CONCLUSIONS
  Food did not affect canagliflozin bioavailability parameters (Cmax and AUCs) or AUCs of metformin. The Cmax of metformin was decreased by 16%, which is not considered clinically meaningful. The canagliflozin/metformin FDC tablet is recommended to be taken with meals to reduce the symptoms of gastrointestinal intolerability associated with metformin.
authors.forename: Joseph
authors.initials: J
authors.lastname: Murphy
authors.forename: Shean-Sheng
authors.initials: SS
authors.lastname: Wang
authors.forename: Hans
authors.initials: H
authors.lastname: Stieltjes
authors.forename: Ewa
authors.initials: E
authors.lastname: Wajs
authors.forename: Damayanthi
authors.initials: D
authors.lastname: Devineni
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D000068896:Canagliflozin; D018592:Cross-Over Studies; D004338:Drug Combinations; D005215:Fasting / Q000097:blood; D005260:Female; D018565:Food-Drug Interactions; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D019518:Postprandial Period; D013607:Tablets; D013810:Therapeutic Equivalency; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D005960:Glucosides; D007004:Hypoglycemic Agents; D013607:Tablets; D013876:Thiophenes; D000068896:Canagliflozin; D008687:Metformin