An Open-label, Multicenter Study of the Safety, Pharmacokinetics, and Efficacy of Buprenorphine Transdermal System (BTDS) in Children From 7 to 16 Years of Age, Inclusive, Who Require Continuous Opioid Analgesia for Moderate to Severe Pain

The Number of Participants With Adverse Events as a Measure of Safety

时间窗: Up to 28 weeks

Safety assessments consisted of reports of AEs, vital signs (blood pressure, pulse rate, respiratory rate, and temperature), weight, hemoglobin-oxygen saturation measured by pulse oximetry (SpO2), clinical laboratory tests, somnolence (assessed by the University of Michigan Sedation Scale \[UMSS\]), conventional 12-lead electrocardiograms (ECGs), and 24-hour digital 12-lead ECGs (Holter monitor). Safety variables were summarized descriptively within age group for the safety population.

Pharmacokinetics (PK) of Buprenorphine Following Transdermal Administration: Apparent Volume of Distribution (Vc/F)

时间窗: Day 1, end of week 1, days 9/10, end of week 2, and end of week 4 or at discontinuation prior to end of study visit

The population PK (PopPK) of BTDS buprenorphine in pediatric patients ages 7 to 16 years was described by a 2-compartment model with sequential zero- and first-order absorption from the patch. A fixed allometric relationship was used to describe the effects of changes in ideal body weight (IBW) across pediatric patients on all clearance and volume parameters. Given the sparse sample collections, small sample size, and complexity of the absorption process with the patch formulation, this PopPK model was fit to the pediatric data using nonlinear mixed effects modeling (NONMEM) Bayes method with selective use of priors from previous adult PopPK results. Estimates of fixed effects from the final model were used to calculate the Vc/F after patch dosing given the covariate distribution in the PopPK dataset and the typical weights from children in the National Health and Nutrition Examination Survey (NHANES) dataset.

Pharmacokinetics (PK) of Buprenorphine Following Transdermal Administration: Apparent Clearance (CL/F)

时间窗: Day 1, end of week 1, days 9/10, end of week 2, and end of week 4 or at discontinuation prior to end of study visit

The population PK (PopPK) of BTDS buprenorphine in pediatric patients ages 7 to 16 years was described by a 2-compartment model with sequential zero- and first-order absorption from the patch. A fixed allometric relationship was used to describe the effects of changes in ideal body weight (IBW) across pediatric patients on all clearance and volume parameters. Given the sparse sample collections, small sample size, and complexity of the absorption process with the patch formulation, this PopPK model was fit to the pediatric data using nonlinear mixed effects modeling (NONMEM) Bayes method with selective use of priors from previous adult PopPK results. Estimates of fixed effects from the final model were used to calculate the CL/F after patch dosing given the covariate distribution in the PopPK dataset and the typical weights from children in the National Health and Nutrition Examination Survey (NHANES) dataset.