SEOUL, Korea I January 21, 2013 I South Korea’s Dong-A Pharmaceutical announced positive top-line results from phase 2 clinical trial of its DPP-4 inhibitor, Evogliptin (coded as DA-1229).
The multi-center phase 2 clinical trial conducted in Korea was a randomized, double-blind, placebo-controlled, therapeutic exploratory clinical study to investigate efficacy and safety of Evogliptin. A total of 157 patients with type 2 diabetes who had inadequate glycaemic control on diet and exercise were administered with either placebo or one of the three doses of Evogliptin (2.5, 5, 10 mg) once daily for 12 weeks.
Evogliptin met primary endpoint at all dose groups by significantly lowering HbA1c level from baseline compared to placebo group. The change of HbA1c level from baseline was -0.56%, -0.66%, -0.61% in Evogliptin 2.5, 5, 10 mg group, respectively, while the change was -0.09% in placebo group (P < 0.0001). In addition, the change of Fasting Plasma Glucose (FPG) at 12 weeks was -14.10, -15.16, -11.86 mg/dL in 2.5, 5, 10 mg group, respectively, which presents significant improvements in comparison with +6.38 mg/dL in placebo group (P=0.0003). AUC of plasma glucose for 2 hours in Oral Glucose Tolerance Test (OGTT) was also significantly reduced from baseline in Evogliptin-treated groups (P < 0.001).
Evogliptin was proven to be safe and well tolerated at all dose groups with no severe ADRs found in the phase 2 clinical trial. There were no statistically significant differences in the incidence rates of ADRs between Evogliptin treatment groups and placebo group. Furthermore, no pancreatitis-related AEs were reported in this trial.
Collectively, the dose regimen of 5 mg once daily was selected for phase 3 clinical trials. This is an expected result because Evogliptin was already found to be highly potent in the previous studies. The PK-PD analysis in mice, rats, dogs, and monkeys showed that effective plasma concentrations (EC80) of DA-1229 ranged from 3.3 to 19.3 ng/mL, which were lower than those of a leading comparator drug by 3 to 36 folds. In phase 1 clinical trial, a single dose of Evogliptin 5 mg inhibited DPP-4 activity more than 80%, and repeated once-daily dose of Evogliptin 5 mg maintained DPP-4 inhibition more than 24 hours.
Evogliptin features in its low renal excretion. As PK studies in animal models and healthy human volunteers presented low renal elimination, it is highly expected Evogliptin does not need dose titration in patients with renal impairment. Further PK study in renal impaired patients is planned for firm confirmation on this advantage. In addition, not only antidiabetic functions, Evogliptin also showed potentials to prevent and improve fatty liver and dyslipidemia in a high-fat diet induced obese mice model. Considering that there are lots of diabetic patients with obesity and dyslipidemia, Evogliptin is expected to be more helpful for those patients.
Dong-A pharmaceutical signed license agreements of Evogliptin with Chinese and Indian pharmaceutical companies last year which granted the rights of Evogliptin in the territory of China and India/ Nepal, respectively.
Dong-A plans to initiate phase 3 clinical trials in the first half of this year using 5 mg dose of Evogliptin as monotherapy and combination therapy with metformin, and expects its launch in 2016 in Korea. Dong-A is actively seeking promising licensing partner companies for development and commercialization of Evogliptin for the territory of any countries except China and India/Nepal. (contact: jeje@donga.co.kr).
SOURCE: Dong-A Pharmaceutical
Post Views: 303
SEOUL, Korea I January 21, 2013 I South Korea’s Dong-A Pharmaceutical announced positive top-line results from phase 2 clinical trial of its DPP-4 inhibitor, Evogliptin (coded as DA-1229).
The multi-center phase 2 clinical trial conducted in Korea was a randomized, double-blind, placebo-controlled, therapeutic exploratory clinical study to investigate efficacy and safety of Evogliptin. A total of 157 patients with type 2 diabetes who had inadequate glycaemic control on diet and exercise were administered with either placebo or one of the three doses of Evogliptin (2.5, 5, 10 mg) once daily for 12 weeks.
Evogliptin met primary endpoint at all dose groups by significantly lowering HbA1c level from baseline compared to placebo group. The change of HbA1c level from baseline was -0.56%, -0.66%, -0.61% in Evogliptin 2.5, 5, 10 mg group, respectively, while the change was -0.09% in placebo group (P < 0.0001). In addition, the change of Fasting Plasma Glucose (FPG) at 12 weeks was -14.10, -15.16, -11.86 mg/dL in 2.5, 5, 10 mg group, respectively, which presents significant improvements in comparison with +6.38 mg/dL in placebo group (P=0.0003). AUC of plasma glucose for 2 hours in Oral Glucose Tolerance Test (OGTT) was also significantly reduced from baseline in Evogliptin-treated groups (P < 0.001).
Evogliptin was proven to be safe and well tolerated at all dose groups with no severe ADRs found in the phase 2 clinical trial. There were no statistically significant differences in the incidence rates of ADRs between Evogliptin treatment groups and placebo group. Furthermore, no pancreatitis-related AEs were reported in this trial.
Collectively, the dose regimen of 5 mg once daily was selected for phase 3 clinical trials. This is an expected result because Evogliptin was already found to be highly potent in the previous studies. The PK-PD analysis in mice, rats, dogs, and monkeys showed that effective plasma concentrations (EC80) of DA-1229 ranged from 3.3 to 19.3 ng/mL, which were lower than those of a leading comparator drug by 3 to 36 folds. In phase 1 clinical trial, a single dose of Evogliptin 5 mg inhibited DPP-4 activity more than 80%, and repeated once-daily dose of Evogliptin 5 mg maintained DPP-4 inhibition more than 24 hours.
Evogliptin features in its low renal excretion. As PK studies in animal models and healthy human volunteers presented low renal elimination, it is highly expected Evogliptin does not need dose titration in patients with renal impairment. Further PK study in renal impaired patients is planned for firm confirmation on this advantage. In addition, not only antidiabetic functions, Evogliptin also showed potentials to prevent and improve fatty liver and dyslipidemia in a high-fat diet induced obese mice model. Considering that there are lots of diabetic patients with obesity and dyslipidemia, Evogliptin is expected to be more helpful for those patients.
Dong-A pharmaceutical signed license agreements of Evogliptin with Chinese and Indian pharmaceutical companies last year which granted the rights of Evogliptin in the territory of China and India/ Nepal, respectively.
Dong-A plans to initiate phase 3 clinical trials in the first half of this year using 5 mg dose of Evogliptin as monotherapy and combination therapy with metformin, and expects its launch in 2016 in Korea. Dong-A is actively seeking promising licensing partner companies for development and commercialization of Evogliptin for the territory of any countries except China and India/Nepal. (contact: jeje@donga.co.kr).
SOURCE: Dong-A Pharmaceutical
Post Views: 303
