A randomized clinical trial to evaluate the single-dose pharmacokinetics, pharmacodynamics, and safety of sitagliptin in pediatric patients with type 2 diabetes
| Autor: | Xiujiang S. Li, Lata Maganti, Tracie L. Miller, Wen-Lin Luo, Henry Rodriguez, Susan J. Lee, Daniel Tatosian, Philip Zeitler, Iain P. Fraser, Jaclyn K. Patterson, Mark S. Kipnes, Naomi D. Neufeld, Jocelyn Gilmartin, S. Aubrey Stoch, Larry A. Fox |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism Cmax 030209 endocrinology & metabolism Type 2 diabetes Placebo Gastroenterology law.invention 03 medical and health sciences 0302 clinical medicine Double-Blind Method Pharmacokinetics Randomized controlled trial law Internal medicine Internal Medicine Humans Hypoglycemic Agents Medicine 030212 general & internal medicine Age of Onset Child Dose-Response Relationship Drug business.industry Body Weight Sitagliptin Phosphate Age Factors medicine.disease Diabetes Mellitus Type 2 Tolerability Sitagliptin Pharmacodynamics Pediatrics Perinatology and Child Health Female business medicine.drug |
| Zdroj: | Pediatric Diabetes. 20:48-56 |
| ISSN: | 1399-543X |
| DOI: | 10.1111/pedi.12790 |
| Popis: | Objective To evaluate the single-dose pharmacokinetics (PK), pharmacodynamics (PD), and safety of sitagliptin in pediatric patients with type 2 diabetes mellitus (T2DM). Study design This was a randomized, placebo-controlled, double-blind evaluation of sitagliptin in 35 patients 10 to 17 years old with T2DM at 7 clinical research sites. The safety, tolerability, PK, and PD (dipeptidyl peptidase-4 [DPP-4] inhibition and aspects of glucose metabolism) of single doses of 50, 100, and 200 mg were assessed. Appropriate transformations on the PK parameters were used and back-transformed summary statistics are reported. Results Adverse experiences were reported by eight study participants; all were of mild intensity except one (intravenous site pain of moderate intensity). PK characteristics in the young patients were comparable to reference adult data, with geometric mean ratios (youths/adults) for AUC0-∞ , Cmax , and C24hr of 0.82, 1.04, and 0.74, respectively. Single doses of 50, 100, and 200 mg sitagliptin inhibited 67.2%, 73.8%, and 81.2% of plasma DPP-4 activity over 24 hours, respectively. Least squares (LS) mean glucose concentrations 2 hours after an oral glucose tolerance test or a meal tolerance test decreased in study participants treated with sitagliptin, compared to placebo, while active LS mean glucagon-like peptide 1 concentrations increased significantly at all sitagliptin doses in both tests. Conclusions Single doses of sitagliptin as high as 200 mg were generally well tolerated in 10- to 17-year-old male and female study participants with T2DM, and a daily sitagliptin dose of 100 mg is appropriate for evaluation in Phase III safety and efficacy studies in pediatric patients with T2DM. (ClinicalTrials.gov: NCT00730275). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|