[Show abstract][Hide abstract] ABSTRACT: The pharmacokinetics of some medications may be affected by differences in race and ethnicity, which can lead to suboptimal outcomes. The present study was conducted to assess the single- and multiple-dose pharmacokinetics of saxagliptin in healthy Chinese subjects living in China.
This was an open-label, 9-day study conducted at the Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China. Sixteen healthy Chinese subjects of both sexes between 21 and 33 years of age were administered saxagliptin 5 mg orally on day 1, then once daily on days 3-7. Pharmacokinetic variables for saxagliptin (primary outcome) and its active metabolite, 5-hydroxy saxagliptin (secondary outcome), after single and multiple oral doses of saxagliptin were assessed. Safety was also assessed.
Saxagliptin was absorbed rapidly (median time to reach maximum concentration [t(max)]: 0.5 and 1 hour on days 1 and 7, respectively), and its pharmacologically active metabolite, 5-hydroxy saxagliptin, appeared in plasma (median t(max): 1.0 and 1.5 hours, respectively). Plasma exposure to 5-hydroxy saxagliptin was approximately 2- to 3-fold higher than exposure to saxagliptin. Plasma concentration-time profiles for saxagliptin and 5-hydroxy saxagliptin were similar on days 1 and 7, with no evidence of drug accumulation on repeated dosing. The elimination half-lives (t(½)) for saxagliptin and 5-hydroxy saxagliptin were approximately 3 and 4 hours, respectively, with renal excretion as the primary route of elimination. After single and multiple dosing, 54.48% and 52.60%, respectively, of the administered saxagliptin dose was recovered in urine as unchanged drug or 5-hydroxy saxagliptin. Saxagliptin was generally well tolerated. Six (37.5%) subjects experienced an adverse event (AE). All AEs were mild in intensity and judged by the investigator as not related to the study medication. There were no deaths, serious AEs, discontinuations due to AEs, or other clinically significant AEs during this study.
Saxagliptin 5 mg (single dose and once-daily doses for 5 days) was generally well tolerated; the pharmacokinetics of saxagliptin and 5-hydroxy saxagliptin in healthy Chinese subjects were consistent with previous assessments in the saxagliptin clinical development program.
ClinicalTrials.gov identifier: NCT00770302.
No preview · Article · Jun 2012 · Clinical Drug Investigation
[Show abstract][Hide abstract] ABSTRACT: Few studies have assessed the use of new oral anti-diabetic agents in Asian populations. This study assesses the efficacy and safety of saxagliptin versus placebo in Asian patients with type 2 diabetes mellitus (T2DM).
Five hundred sixty-eight drug-naïve adult patients with T2DM and glycated haemoglobin levels (HbA(1c)) of 7.0-10.0% (53-86 mmol/mol) were randomized 1 : 1 to receive saxagliptin 5 mg daily or placebo. Efficacy endpoints included changes from baseline to week 24 in HbA(1c) , fasting plasma glucose (FPG), post-prandial glucose area under the curve from 0 to 180 min (PPG AUC(0-180)), and the proportion of patients achieving HbA(1c) <7.0% (53 mmol/mol). Adverse events (AEs) and serious AEs (SAEs) were evaluated.
Saxagliptin provided statistically significant adjusted mean decreases from baseline to week 24 compared with placebo, respectively, in HbA(1c) (-0.84% [-9 mmol/mol] versus -0.34% [-4 mmol/mol]; p < 0.0001), FPG (-0.90 versus -0.17 mmol/L; p < 0.0001), and PPG AUC(0-180) (-417 versus -235 mmol · min/L; p = 0.0010). A significantly greater proportion of patients achieved a therapeutic glycaemic response (HbA(1c) <7.0% [53 mmol/mol]) with saxagliptin (45.8%) versus placebo (28.8%; p < 0.0001). The proportions of patients who experienced ≥1 AE (excluding hypoglycaemia) was 43.3% for saxagliptin and 35.6% for placebo. Few patients in either treatment group experienced an SAE (2.8%, saxagliptin; 1.4%, placebo). A low proportion of patients reported hypoglycaemic events (1.8%, saxagliptin; 0.7%, placebo).
Saxagliptin improved glycaemic control and was well tolerated in drug-naïve Asian patients with T2DM.
No preview · Article · Mar 2012 · Diabetes/Metabolism Research and Reviews
[Show abstract][Hide abstract] ABSTRACT: To assess efficacy and safety of saxagliptin added to metformin versus placebo plus metformin in Asian patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on metformin alone.
Adults (HbA(1c) 7.0-10.0%, on stable metformin ≥ 1500 mg/day) were randomized 1:1 to saxagliptin 5mg daily plus metformin (n = 283) or placebo plus metformin (n = 287). The primary end point was HbA(1c) change from baseline to Week 24.
Saxagliptin plus metformin provided significant adjusted mean decreases versus placebo plus metformin (p ≤ 0.0052) in HbA(1c) (-0.78% versus -0.37%), fasting plasma glucose (-1.14 mmol/L versus -0.58 mmol/L), and postprandial glucose area under the curve from 0 to 180 min (-315 mmol min/L versus -160 mmol min/L). Significantly more saxagliptin-treated patients achieved a therapeutic glycemic response (HbA(1c)<7.0%) (46.5% versus 30.5%; p = 0.0001). The proportion of patients experiencing adverse events (excluding hypoglycemia) was similar for saxagliptin plus metformin (42.8%) versus placebo plus metformin (40.8%). Hypoglycemic events were reported in 1.4% of patients in each group.
Saxagliptin added to metformin significantly improved glycemic control and was well tolerated in Asian patients with T2DM who had inadequate glycemic control with metformin and diet and lifestyle modification.
No preview · Article · Aug 2011 · Diabetes research and clinical practice