Liraglutide in an Adolescent Population with Obesity: A Randomized, Double-Blind, Placebo-Controlled 5-Week Trial to Assess Safety, Tolerability, and Pharmacokinetics of Liraglutide in Adolescents Aged 12-17 Years.

OBJECTIVES: To investigate the safety, tolerability, and pharmacokinetics of liraglutide in adolescents with obesity. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial. Twenty-one subjects, aged 12-17 years and Tanner stage 2-5, with obesity (body mass index [BMI] corresponding to both a BMI ≥95th percentile for age and sex and to a BMI of ≥30 kg/m2 for adults; additionally, BMI was ≤45 kg/m2) were randomized (2:1) to receive 5 weeks of treatment with liraglutide (0.6 mg with weekly dose increase to a maximum of 3.0 mg for the last week) (n = 14) or placebo (n = 7). The primary endpoint was number of treatment-emergent adverse events (TEAEs). Secondary endpoints included safety measures, and pharmacokinetic and pharmacodynamic endpoints. RESULTS: All participants receiving liraglutide, and 4 receiving placebo (57.1%), had at least 1 TEAE. The most common TEAEs were gastrointestinal disorders. No severe TEAEs, TEAE-related withdrawals, or deaths occurred. Twelve hypoglycemic episodes occurred in 8 participants receiving liraglutide and 2 in 1 participant receiving placebo. No severe hypoglycemic episodes were reported. Liraglutide exposure in terms of trough concentration increased with dose, although dose proportionality was confounded by unexpectedly low trough concentration values at the 2.4 mg dose. Exposure in terms of model-derived area under the plasma concentration time curve from 0 to 24 hours after dose in steady state was similar to that in adults with obesity. CONCLUSIONS: Liraglutide had a similar safety and tolerability profile compared with adults when administered to adolescents with obesity, with no unexpected safety/tolerability issues. Results suggest that the dosing regimen approved for weight management in adults may be appropriate for use in adolescents. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01789086.

Comparable liraglutide pharmacokinetics in pediatric and adult populations with type 2 diabetes: a population pharmacokinetic analysis.

BACKGROUND AND OBJECTIVE: The safety, tolerability, and pharmacokinetics of the once-daily human glucagon-like peptide-1 (GLP-1) analog liraglutide have been evaluated in pediatric patients aged greater than 10 years with type 2 diabetes (T2D). In this study, a population pharmacokinetic analysis was compared to the pediatric pharmacokinetic data with those from two clinical pharmacology trials in adults with T2D. METHODS: A one-compartment pharmacokinetic model previously found to adequately describe the pharmacokinetics of liraglutide in adults with T2D was applied to the evaluation of 13 pediatric subjects (10-17 years of age) with T2D. Steady-state estimates for apparent clearance (CL/F) for individual subjects and corresponding dose were used to derive the area under the plasma-concentration time curve from 0-24 h (AUC24) and investigate dose proportionality in the pediatric trial. A covariate analysis evaluated the effects of body weight, gender, and age category (pediatric/adult) on liraglutide exposure. RESULTS: Dose proportionality in the dose range of 0.3-1.8 mg was indicated by the model-derived AUC24 slope: 1.05 (95% CI 0.96-1.15). Consistent with findings from adult trials, body weight and gender were relevant covariates for liraglutide exposure in the pediatric population. The CL/F estimates, and thus exposure, for the pediatric subjects with T2D were similar to those in the adult trials. CONCLUSION: Based on this population pharmacokinetic analysis, the liraglutide dose regimen that was found to be clinically effective in adults is predicted to achieve the same range of exposure in the pediatric population (10-17 years of age) with a pre-trial body weight range of 57-214 kg.