Background Barth Syndrome (BTHS) is a rare genetic disorder that presents as a complex of debilitating symptoms and reduced life expectancy. Well-developed, BTHS-specific assessments measuring primary signs and symptoms of BTHS are not currently available, making it difficult to evaluate treatment effects in BTHS clinical studies. The objective of this research was to develop symptom-focused patient-reported outcome (PRO) measures for use in clinical studies with adolescents and adults with BTHS. Methods Concept elicitation interviews (CEIs) with pediatric (n = 18, age < 16 years) and adult (n = 15, age ≥ 16 years) individuals with BTHS and/or their caregivers were conducted to identify signs and symptoms relevant to BTHS and important to individuals with the condition. Based on CEI results, questionnaire construction activities were conducted to create unique adolescent and adult versions of the Barth Syndrome-Symptom Assessment (BTHS-SA). The questionnaires were evaluated in cognitive debriefing interviews (CDIs) with adolescents (n = 12; age 12- < 16 years) and adults (n = 12; age ≥ 16 years) with BTHS to assess relevance and readability of the tools. Results During the CEIs, a total of 48 and 40 signs and symptoms were reported by the pediatric and adult groups, respectively; 31 were reported by both age groups. Fatigue/tiredness and muscle weakness were the symptoms most frequently reported by both pediatric and adult patients with BTHS as important to improve with an effective treatment. The CEI results informed construction of a nine-item version of the BTHS-SA for adolescents and an eight-item version for adults. Developed for daily administration, each version asks respondents to rate symptom severity “at its worst” over the 24 h prior to administration. CDIs with both adolescents and adults with BTHS demonstrated that each BTHS-SA version was reflective of the disease experience and that respondents could interpret the questionnaire as intended and provide responses that accurately reflected their symptom experience. Conclusions The BTHS-SA adolescent and adult versions are content-valid PRO measures that can be used to evaluate severity of disease-specific symptoms in future clinical trials. Given the lack of available and well-developed assessments in this underserved therapeutic area, these tools fulfill a need for clinical researchers developing treatments for individuals with BTHS.
Ceftolozane/tazobactam, a novel antibacterial with potent activity against Gram-negative pathogens, was developed for treatment of complicated urinary tract infections, including pyelonephritis, and intra-abdominal infections. A phase 1 pharmacokinetic (PK) study of ceftolozane/tazobactam in healthy Japanese, Chinese, and white volunteers was conducted to assess the potential effect of ethnicity on PK. The PK of ceftolozane, tazobactam, and tazobactam metabolite M1 was compared after single 1.5- and 3-g intravenous doses of ceftolozane/tazobactam. Ten Japanese, nine Chinese, and ten white subjects were enrolled, and 27 completed all doses of study medication. Dose-normalized PK parameters for ceftolozane and tazobactam were similar among Japanese, Chinese, and white subjects (at 1.5-g and 3-g doses, ceftolozane area under the plasma concentration-time curve from zero to infinity [AUC ] = 166.3, 165.9, and 185.5 h μg/mL, respectively, and 157.7, 158.5, and 181.2 h μg/mL, respectively; tazobactam AUC = 48.5, 43.2, and 50.1 h μg/mL, respectively, and 47.3, 43.7, and 50.0 h μg/mL, respectively. The 90% CIs of their ratio estimates were within the range 0.80 to 1.25 with the exception of AUC for ceftolozane after the 3-g dose (0.79). The cumulative amount of ceftolozane and tazobactam excreted in urine was similar among ethnic groups. For all groups, treatment-emergent adverse events (AEs) were mild; no deaths or serious AEs were reported. The PK of ceftolozane/tazobactam was approximately dose proportional (i.e. doubling the dose approximately doubles the exposure) and similar among the groups. No dosage adjustment is needed for ceftolozane/tazobactam in Japanese and Chinese patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.