OBJECTIVES: To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of pramlintide in treating adolescents with type 1 diabetes. STUDY DESIGN:Twelve subjects (9 females, 3 males, age 12 to 17 years; A1C, 8.4%; body mass index, 25 kg/m(2)) were randomized to pramlintide (15 or 30 microg) or placebo administered before a standardized breakfast. Insulin lispro (50% of usual mealtime dose) was injected separately. Acetaminophen (1000 mg) was administered orally to provide an indicator of gastric emptying rate. RESULTS: In 9 evaluable subjects, plasma pramlintide concentrations increased dose-proportionately; mean peak plasma concentration (C(max)) (15-microg dose, 93 +/- 9 pg/mL; 30-microg dose, 202 +/- 21 pg/mL) occurred approximately 0.3 h (median time to peak concentration) after administration. Pramlintide reduced incremental area under the concentration curve (AUC(0-3h)) for glucagon and glucose versus placebo (glucagon: 15-microg dose, 4 +/- 7 pg(*)h/mL; 30-microg dose, 5 +/- 7 pg(*)h/mL; placebo, 35 +/- 9 pg(*)h/mL; glucose: 15-microg dose, 129 +/- 43 mg(*)h/dL; 30-microg dose, 132 +/- 37 mg(*)h/dL; placebo, 217 +/- 56 mg(*)h/dL). Acetaminophen C(max) decreased with pramlintide; median T(max) was delayed by approximately 2.6- to 3.8-fold. Pramlintide was well tolerated, and no treatment-related adverse events occurred. CONCLUSIONS:Pramlintide reduced postprandial glucagon and glucose excursions and slowed gastric emptying in adolescents with type 1 diabetes, with no treatment-related adverse events. Long-term studies evaluating the efficacy and safety of pramlintide in adolescents are warranted.
RCT Entities:
OBJECTIVES: To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of pramlintide in treating adolescents with type 1 diabetes. STUDY DESIGN: Twelve subjects (9 females, 3 males, age 12 to 17 years; A1C, 8.4%; body mass index, 25 kg/m(2)) were randomized to pramlintide (15 or 30 microg) or placebo administered before a standardized breakfast. Insulin lispro (50% of usual mealtime dose) was injected separately. Acetaminophen (1000 mg) was administered orally to provide an indicator of gastric emptying rate. RESULTS: In 9 evaluable subjects, plasma pramlintide concentrations increased dose-proportionately; mean peak plasma concentration (C(max)) (15-microg dose, 93 +/- 9 pg/mL; 30-microg dose, 202 +/- 21 pg/mL) occurred approximately 0.3 h (median time to peak concentration) after administration. Pramlintide reduced incremental area under the concentration curve (AUC(0-3h)) for glucagon and glucose versus placebo (glucagon: 15-microg dose, 4 +/- 7 pg(*)h/mL; 30-microg dose, 5 +/- 7 pg(*)h/mL; placebo, 35 +/- 9 pg(*)h/mL; glucose: 15-microg dose, 129 +/- 43 mg(*)h/dL; 30-microg dose, 132 +/- 37 mg(*)h/dL; placebo, 217 +/- 56 mg(*)h/dL). Acetaminophen C(max) decreased with pramlintide; median T(max) was delayed by approximately 2.6- to 3.8-fold. Pramlintide was well tolerated, and no treatment-related adverse events occurred. CONCLUSIONS: Pramlintide reduced postprandial glucagon and glucose excursions and slowed gastric emptying in adolescents with type 1 diabetes, with no treatment-related adverse events. Long-term studies evaluating the efficacy and safety of pramlintide in adolescents are warranted.
Authors: Stuart A Weinzimer; Jennifer L Sherr; Eda Cengiz; Grace Kim; Jessica L Ruiz; Lori Carria; Gayane Voskanyan; Anirban Roy; William V Tamborlane Journal: Diabetes Care Date: 2012-07-18 Impact factor: 19.112