Evaluating the Acceptability, Swallowability, and Palatability of Film-Coated Mini-Tablet Formulation in Young Children: Results from an Open-Label, Single-Dose, Cross-Over Study
Juliane Münch,
Isabelle Sessler,
Hans Martin Bosse,
Manfred Wargenau,
Janine D. Dreesen,
Giulio Loforese,
Nicholas J. A. Webb,
Rama Sivasubramanian,
Sibylle Reidemeister,
Philipp Lustenberger,
Viviane Klingmann
Affiliations
Juliane Münch
Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Isabelle Sessler
Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Hans Martin Bosse
Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Manfred Wargenau
M.A.R.C.O. GmbH & Co. KG, Institute for Clinical Research and Statistics, 40211 Düsseldorf, Germany
Janine D. Dreesen
M.A.R.C.O. GmbH & Co. KG, Institute for Clinical Research and Statistics, 40211 Düsseldorf, Germany
Giulio Loforese
Global Drug Development, Novartis Pharma AG, 4002 Basel, Switzerland
Nicholas J. A. Webb
Global Drug Development, Novartis Pharma AG, 4002 Basel, Switzerland
Rama Sivasubramanian
Global Drug Development, Novartis Healthcare Pvt. Ltd., Hyderabad 500081, India
Sibylle Reidemeister
Global Drug Development, Novartis Pharma AG, 4002 Basel, Switzerland
Philipp Lustenberger
Global Drug Development, Novartis Pharma AG, 4002 Basel, Switzerland
Viviane Klingmann
Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Mini-tablets are advantageous over liquid formulations in overcoming challenges related to stability, taste, and dosage. This open-label, single-dose, cross-over study investigated the acceptability and safety of drug-free, film-coated mini-tablets in children aged 1 month–6 years (stratified: 4–6 years, 2–<4 years, 1–<2 years, 6–<12 months, and 1–<6 months), and their preference for swallowing either a high quantity of 2.0 mm or a low quantity of 2.5 mm diameter mini-tablets. The primary endpoint was acceptability derived from swallowability. The secondary endpoints were investigator-observed palatability, acceptability as a composite endpoint derived from both swallowability and palatability, and safety. Of 320 children randomized, 319 completed the study. Across all tablet sizes, quantities and age groups, acceptability rates based on swallowability were high (at least 87%). Palatability was rated as “pleasant/neutral” in 96.6% of children. The acceptability rates as per the composite endpoint were at least 77% and 86% for the 2.0 mm and 2.5 mm film-coated mini-tablets, respectively. No adverse events or deaths were reported. Recruitment in the 1–<6-months group was stopped early due to coughing—evaluated as “choked on” in three children. Both 2.0 mm and 2.5 mm film-coated mini-tablets are suitable formulations for young children.
