OBJECTIVE: To investigate safety, pharmacokinetics and pharmacodynamics of albiglutide in Japanese subjects with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: This randomized, single-blind, placebo-controlled study examined four doses/dose schedules of subcutaneously (sc) administered albiglutide: 15 mg weekly, 30 mg weekly, 50 mg biweekly, and 100 mg monthly (cohorts A-D, respectively) in 40 subjects (mean age 54.5 years, mean range of glycosylated hemoglobin [HbA(1c)] 7.1-8.3%), over a 4-week treatment period. MAIN OUTCOME MEASURES: Safety parameters, including adverse events, clinical laboratory tests, vital signs, and 12-lead electrocardiogram; plasma concentrations of albiglutide; and pharmacodynamic parameters, including change from baseline and weighted mean AUC(0-4) in plasma glucose, glucagon, insulin, and C-peptide levels. CLINICAL TRIAL REGISTRATION: NCT00530309. RESULTS: At day 29, mean changes from baseline (vs. placebo) in fasting plasma glucose (FPG) were: cohort A, -1.92 mmol/L; B, -1.98 mmol/L; C, -1.74 mmol/L; D, -0.73 mmol/L; changes in weighted mean glucose AUC(0-4) were: cohort A, -2.86 mmol/L; B, -3.58 mmol/L; C, -2.51 mmol/L; D, -1.44 mmol/L (for FPG and AUC(0-4), all p < or = 0.002 except 100 mg sc monthly, p = NS); changes from baseline HbA(1c) were: cohort A, -0.58%; B, -0.57%; C, -0.63%; and D, -0.51% (all p < 0.03). Albiglutide sc had a median half-life of 5.3 days, plasma apparent systemic clearance of 68.7 mL/h, and apparent volume of distribution of 12.6 L. Incidence of adverse events was low and comparable to sc placebo in all albiglutide treatment arms except 100 mg sc monthly, where gastrointestinal (GI) adverse events were most common. Limitations of this study include the small sample size, short treatment duration, and enrollment of predominantly male subjects. CONCLUSIONS: Weekly and biweekly albiglutide improved glycemic control and were well-tolerated in Japanese subjects with type 2 diabetes mellitus.
RCT Entities:
OBJECTIVE: To investigate safety, pharmacokinetics and pharmacodynamics of albiglutide in Japanese subjects with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: This randomized, single-blind, placebo-controlled study examined four doses/dose schedules of subcutaneously (sc) administered albiglutide: 15 mg weekly, 30 mg weekly, 50 mg biweekly, and 100 mg monthly (cohorts A-D, respectively) in 40 subjects (mean age 54.5 years, mean range of glycosylated hemoglobin [HbA(1c)] 7.1-8.3%), over a 4-week treatment period. MAIN OUTCOME MEASURES: Safety parameters, including adverse events, clinical laboratory tests, vital signs, and 12-lead electrocardiogram; plasma concentrations of albiglutide; and pharmacodynamic parameters, including change from baseline and weighted mean AUC(0-4) in plasma glucose, glucagon, insulin, and C-peptide levels. CLINICAL TRIAL REGISTRATION: NCT00530309. RESULTS: At day 29, mean changes from baseline (vs. placebo) in fasting plasma glucose (FPG) were: cohort A, -1.92 mmol/L; B, -1.98 mmol/L; C, -1.74 mmol/L; D, -0.73 mmol/L; changes in weighted mean glucose AUC(0-4) were: cohort A, -2.86 mmol/L; B, -3.58 mmol/L; C, -2.51 mmol/L; D, -1.44 mmol/L (for FPG and AUC(0-4), all p < or = 0.002 except 100 mg sc monthly, p = NS); changes from baseline HbA(1c) were: cohort A, -0.58%; B, -0.57%; C, -0.63%; and D, -0.51% (all p < 0.03). Albiglutide sc had a median half-life of 5.3 days, plasma apparent systemic clearance of 68.7 mL/h, and apparent volume of distribution of 12.6 L. Incidence of adverse events was low and comparable to sc placebo in all albiglutide treatment arms except 100 mg sc monthly, where gastrointestinal (GI) adverse events were most common. Limitations of this study include the small sample size, short treatment duration, and enrollment of predominantly male subjects. CONCLUSIONS: Weekly and biweekly albiglutide improved glycemic control and were well-tolerated in Japanese subjects with type 2 diabetes mellitus.