Capsule and Sprinkle Formulations of Lubiprostone Are Not Biologically Similar in Patients with Functional Constipation

Introduction Lubiprostone capsules are approved for managing three different chronic constipation conditions. A “sprinkle” formulation may facilitate use in individuals with difficulty swallowing capsules. Our objective was to evaluate the bioequivalence, pharmacokinetics (PK), and bioavailability of lubiprostone sprinkles vs lubiprostone capsules, compared with placebo. Methods A 1-week randomized, placebo-controlled, double-blinded, bioequivalence study (study 302) and a single-dose PK and bioavailability crossover study (study 304) were conducted. In study 302, 522 subjects with chronic constipation were randomized to lubiprostone sprinkle 24 μg twice daily (BID), lubiprostone capsule 24 μg BID, or placebo. The primary efficacy endpoint was observed spontaneous bowel movement (SBM) counts (equivalence defined as showing the 90% confidence interval [CI] of the “between-group SBM ratio” to be contained within 0.8–1.25). Study 304 included two cohorts of healthy volunteers randomized to a single 48-μg lubiprostone dose, sprinkle, or capsule (n = 35) or to a single 48-μg sprinkle dose, in fed or fasted state (n = 14). Results Both lubiprostone formulations significantly improved SBM count (sprinkle, 4.82 ± 3.66, P = 0.002; capsule, 5.74 ± 3.79, P