Once versus three times daily dosing of oral budesonide for active Crohn's disease: a double-blind, double-dummy, randomised trial.

BACKGROUND: Oral budesonide 9 mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn's disease. However, there is no precise recommendation for budesonide dosing due to lack of comparative data. A once-daily (OD) 9 mg dose may improve adherence and thereby efficacy. METHODS: An eight-week, double-blind, double-dummy randomised trial compared budesonide 9 mg OD versus 3mg three-times daily (TID) in patients with mild-to-moderately active ileocolonic Crohn's disease. Primary endpoint was clinical remission defined as CDAI <150 at week 8 (last observation carried forward). RESULTS: The final intent-to-treat population comprised 471 patients (238 [9 mg OD], 233 [3 mg TID]). The confirmatory population for the primary endpoint analysis was the interim per protocol population (n=377; 188 [9 mg OD], 189 [3mg TID]), in which the primary endpoint was statistically non-inferior with budesonide 9 mg OD versus 3 mg TID. Clinical remission was achieved in 71.3% versus 75.1%, a difference of -3.9% (95% CI [-14.6%; 6.4%]; p=0.020 for non-inferiority). The mean (SD) time to remission was 21.9 (13.8) days versus 21.4 (14.6) days with budesonide 9 mg OD versus 3 mg TID, respectively. In a subpopulation of 122 patients with baseline SES-CD ulcer score ≥1, complete mucosal healing occurred in 32.8% (21/64) on 9 mg OD and 41.4% (24/58) on 3mg TID; deep remission (mucosal healing and clinical remission) was observed in 26.6% (17/64) and 32.8% (19/58) of patients, respectively. Treatment-emergent suspected adverse drug reactions were reported in 4.6% of 9 mg OD and 4.7% of 3 mg TID patients. CONCLUSIONS: Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3mg TID dosing in mild-to-moderately active Crohn's disease.

Bioequivalence between novel ready-to-use liquid formulations of the recombinant human GH Omnitrope and the original lyophilized formulations for reconstitution of Omnitrope and Genotropin.

OBJECTIVE: Two strengths of a novel ready-to-use liquid preparation of the recombinant human GH (rhGH) Omnitrope were developed to increase the convenience for the patients. DESIGN: Omnitrope 3.3 mg/ml solution or Omnitrope 6.7 mg/ml solution was compared to Omnitrope 5 mg/ml powder and Genotropin 5 mg/ml powder in terms of pharmacokinetics, pharmacodynamics, safety, and local tolerance after a single s.c. dose of 5 mg. METHODS: Two randomized, double-blind, single-dose, three-way crossover studies were carried out in 36 young healthy volunteers each. Endogenous GH secretion was suppressed with a 25-h continuous i.v. infusion of octreotide (40 microg/h) starting 1 h before rhGH administration. RESULTS: Pharmacokinetic parameters were similar for the three treatments in both studies respectively. Bioequivalence criteria were met for area under the concentration-time curve (AUC) and C(max). Likewise, the pharmacodynamic parameters for IGF1, IGF-binding protein 3, and non-esterified fatty acid were similar for all preparations. No differences in adverse events were observed between groups. CONCLUSIONS: Omnitrope 3.3 mg/ml solution, 6.7 mg/ml solution, and 5 mg/ml powder, and Genotropin 5 mg/ml powder are bioequivalent, have similar pharmacokinetic and pharmacodynamic profiles, and are equally safe. Overall, the products can be considered to be therapeutically interchangeable.