Jessica E Pittman1, Umer Khan2, Theresa A Laguna3, Sonya Heltshe4, Christopher H Goss5, Don B Sanders6. 1. Division of Allergy and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States. 2. Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle WA, United States. 3. Division of Pulmonary and Sleep Medicine, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, United States. 4. Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle WA, United States; Division of Pulmonary and Sleep Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, United States. 5. Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle WA, United States; Division of Pulmonary and Sleep Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, United States; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States. 6. Division of Pediatric Pulmonary, Allergy and Sleep Medicine, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, United States. Electronic address: dbsand@iu.edu.
Abstract
BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease characterized by chronic sinopulmonary symptoms and chronic gastrointestinal symptoms that begins in infancy. Children with CF are increasingly being included in clinical trials. In order to fully evaluate the impact of new therapies in future clinical trials, an understanding of baseline adverse event (AE) rates in children with CF is needed. To address this, we determined the rates of common AEs in pediatric patients with CF who participated in two clinical trials. METHODS: We reviewed AEs for placebo recipients in the AZ0004 study and inhaled tobramycin recipients in the Early Pseudomonas Infection Control (EPIC) clinical trial. AEs were categorized based on Medical Dictionary for Regulatory Activities (MedDRA) coding classifications and pooled into common, batched AE descriptors. AE rates were estimated from negative binomial models according to age groups, severity of lung disease, and season. RESULTS: A total of 433 children had 8,266 total AEs reported, or 18.1 (95% CI 17.0, 19.2) AEs per person per year. Respiratory AEs were the most commonly reported AEs, with a rate of 7.6 events per person-year. The total SAE rate was 0.33 per person per-year. Cough was the most commonly reported respiratory AE, with 61% of subjects reporting at least one episode of cough within 4 months. The rate ratio of any AE was higher in Spring, Fall, and Winter, compared with Summer. CONCLUSIONS: AEs occur commonly in pediatric CF clinical trial participants. Season of enrollment could affect AE rates.
BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease characterized by chronic sinopulmonary symptoms and chronic gastrointestinal symptoms that begins in infancy. Children with CF are increasingly being included in clinical trials. In order to fully evaluate the impact of new therapies in future clinical trials, an understanding of baseline adverse event (AE) rates in children with CF is needed. To address this, we determined the rates of common AEs in pediatric patients with CF who participated in two clinical trials. METHODS: We reviewed AEs for placebo recipients in the AZ0004 study and inhaled tobramycin recipients in the Early Pseudomonas Infection Control (EPIC) clinical trial. AEs were categorized based on Medical Dictionary for Regulatory Activities (MedDRA) coding classifications and pooled into common, batched AE descriptors. AE rates were estimated from negative binomial models according to age groups, severity of lung disease, and season. RESULTS: A total of 433 children had 8,266 total AEs reported, or 18.1 (95% CI 17.0, 19.2) AEs per person per year. Respiratory AEs were the most commonly reported AEs, with a rate of 7.6 events per person-year. The total SAE rate was 0.33 per person per-year. Cough was the most commonly reported respiratory AE, with 61% of subjects reporting at least one episode of cough within 4 months. The rate ratio of any AE was higher in Spring, Fall, and Winter, compared with Summer. CONCLUSIONS: AEs occur commonly in pediatric CF clinical trial participants. Season of enrollment could affect AE rates.
Authors: Margaret Rosenfeld; Claire E Wainwright; Mark Higgins; Linda T Wang; Charlotte McKee; Daniel Campbell; Simon Tian; Jennifer Schneider; Steve Cunningham; Jane C Davies Journal: Lancet Respir Med Date: 2018-06-07 Impact factor: 30.700
Authors: Lisa Saiman; Michael Anstead; Nicole Mayer-Hamblett; Larry C Lands; Margaret Kloster; Jasna Hocevar-Trnka; Christopher H Goss; Lynn M Rose; Jane L Burns; Bruce C Marshall; Felix Ratjen Journal: JAMA Date: 2010-05-05 Impact factor: 56.272
Authors: Christopher H Goss; Nicole Mayer-Hamblett; Richard A Kronmal; Judy Williams; Bonnie W Ramsey Journal: J Cyst Fibros Date: 2006-07-07 Impact factor: 5.482
Authors: Michael W Konstan; Edward F McKone; Richard B Moss; Gautham Marigowda; Simon Tian; David Waltz; Xiaohong Huang; Barry Lubarsky; Jaime Rubin; Stefanie J Millar; David J Pasta; Nicole Mayer-Hamblett; Christopher H Goss; Wayne Morgan; Gregory S Sawicki Journal: Lancet Respir Med Date: 2016-12-21 Impact factor: 30.700
Authors: Miriam M Treggiari; George Retsch-Bogart; Nicole Mayer-Hamblett; Umer Khan; Michal Kulich; Richard Kronmal; Judy Williams; Peter Hiatt; Ronald L Gibson; Terry Spencer; David Orenstein; Barbara A Chatfield; Deborah K Froh; Jane L Burns; Margaret Rosenfeld; Bonnie W Ramsey Journal: Arch Pediatr Adolesc Med Date: 2011-09
Authors: Jane C Davies; Claire E Wainwright; Gerard J Canny; Mark A Chilvers; Michelle S Howenstine; Anne Munck; Jochen G Mainz; Sally Rodriguez; Haihong Li; Karl Yen; Claudia L Ordoñez; Richard Ahrens Journal: Am J Respir Crit Care Med Date: 2013-06-01 Impact factor: 21.405
Authors: Nicole Mayer-Hamblett; Margaret Kloster; Bonnie W Ramsey; Michael R Narkewicz; Lisa Saiman; Christopher H Goss Journal: Contemp Clin Trials Date: 2012-11-29 Impact factor: 2.226
Authors: Ranjani Somayaji; Christopher H Goss; Umer Khan; Moni Neradilek; Kathleen M Neuzil; Justin R Ortiz Journal: Clin Infect Dis Date: 2017-06-15 Impact factor: 9.079