A randomized, double-blind, placebo-controlled, phase II clinical trial to investigate the efficacy and safety of oral DA-1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise

Chang Hee Jung, Cheol Young Park, Kyu Joeng Ahn, Nan Hee Kim, Hak Chul Jang, Moon Kyu Lee, Joong Yeol Park, Choon Hee Chung, Kyung Wan Min, Yeon Ah Sung, Jeong Hyun Park, Sung Jin Kim, Hyo Jung Lee, Sung Woo Park

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: DA-1229 is a novel, potent and selective dipeptidyl peptidase-4 (DPP-IV) inhibitor that is orally bioavailable. We aimed to evaluate the optimal dose, efficacy and safety of DA-1229, in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise. Methods: We enrolled 158 patients (mean age, 53 years and a mean BMI, 25.6 kg/m2). The mean baseline fasting plasma glucose level, HbA1c and duration of diabetes were 8.28 mmol/L, 7.6% (60 mmol/mol) and 3.9 years, respectively. After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period, the subjects were randomized into one of four groups for a 12-week active treatment period: placebo, 2.5, 5 or 10 mg of DA-1229. Results: All three doses of DA-1229 significantly reduced HbA1c from baseline compared to the placebo group (-0.09 in the placebo group vs. -0.56, -0.66 and -0.61% in 2.5, 5 and 10-mg groups, respectively) but without any significant differences between the doses. Insulin secretory function, as assessed by homeostasis model assessment β-cell, the insulinogenic index, 2-h oral glucose tolerance test (OGTT) C-peptide and post-OGTT C-peptide area under the curve (AUC)0-2h, significantly improved with DA-1229 treatment. The incidence of adverse events was similar between the treatment groups and DA-1229 did not affect body weight or induce hypoglycaemic events. Conclusions: DA-1229 monotherapy (5 mg for 12 weeks) improved HbA1c, fasting plasma glucose level, OGTT results and β-cell function. This drug was well tolerated in Korean subjects with type 2 diabetes mellitus.

Original languageEnglish
Pages (from-to)295-306
Number of pages12
JournalDiabetes/Metabolism Research and Reviews
Volume31
Issue number3
DOIs
Publication statusPublished - 2015 Mar 1

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Phase II Clinical Trials
Type 2 Diabetes Mellitus
Placebos
Exercise
Diet
Safety
Glucose Tolerance Test
C-Peptide
Fasting
Dipeptidyl Peptidase 4
Glucose
4-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one
Hypoglycemic Agents
Area Under Curve
Homeostasis
Therapeutics
Body Weight
Insulin
Incidence
Pharmaceutical Preparations

Keywords

  • Dose-finding study
  • DPP-IV inhibitor
  • Monotherapy
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

A randomized, double-blind, placebo-controlled, phase II clinical trial to investigate the efficacy and safety of oral DA-1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise. / Jung, Chang Hee; Park, Cheol Young; Ahn, Kyu Joeng; Kim, Nan Hee; Jang, Hak Chul; Lee, Moon Kyu; Park, Joong Yeol; Chung, Choon Hee; Min, Kyung Wan; Sung, Yeon Ah; Park, Jeong Hyun; Kim, Sung Jin; Lee, Hyo Jung; Park, Sung Woo.

In: Diabetes/Metabolism Research and Reviews, Vol. 31, No. 3, 01.03.2015, p. 295-306.

Research output: Contribution to journalArticle

Jung, Chang Hee ; Park, Cheol Young ; Ahn, Kyu Joeng ; Kim, Nan Hee ; Jang, Hak Chul ; Lee, Moon Kyu ; Park, Joong Yeol ; Chung, Choon Hee ; Min, Kyung Wan ; Sung, Yeon Ah ; Park, Jeong Hyun ; Kim, Sung Jin ; Lee, Hyo Jung ; Park, Sung Woo. / A randomized, double-blind, placebo-controlled, phase II clinical trial to investigate the efficacy and safety of oral DA-1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise. In: Diabetes/Metabolism Research and Reviews. 2015 ; Vol. 31, No. 3. pp. 295-306.
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abstract = "Background: DA-1229 is a novel, potent and selective dipeptidyl peptidase-4 (DPP-IV) inhibitor that is orally bioavailable. We aimed to evaluate the optimal dose, efficacy and safety of DA-1229, in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise. Methods: We enrolled 158 patients (mean age, 53 years and a mean BMI, 25.6 kg/m2). The mean baseline fasting plasma glucose level, HbA1c and duration of diabetes were 8.28 mmol/L, 7.6{\%} (60 mmol/mol) and 3.9 years, respectively. After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period, the subjects were randomized into one of four groups for a 12-week active treatment period: placebo, 2.5, 5 or 10 mg of DA-1229. Results: All three doses of DA-1229 significantly reduced HbA1c from baseline compared to the placebo group (-0.09 in the placebo group vs. -0.56, -0.66 and -0.61{\%} in 2.5, 5 and 10-mg groups, respectively) but without any significant differences between the doses. Insulin secretory function, as assessed by homeostasis model assessment β-cell, the insulinogenic index, 2-h oral glucose tolerance test (OGTT) C-peptide and post-OGTT C-peptide area under the curve (AUC)0-2h, significantly improved with DA-1229 treatment. The incidence of adverse events was similar between the treatment groups and DA-1229 did not affect body weight or induce hypoglycaemic events. Conclusions: DA-1229 monotherapy (5 mg for 12 weeks) improved HbA1c, fasting plasma glucose level, OGTT results and β-cell function. This drug was well tolerated in Korean subjects with type 2 diabetes mellitus.",
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AU - Park, Cheol Young

AU - Ahn, Kyu Joeng

AU - Kim, Nan Hee

AU - Jang, Hak Chul

AU - Lee, Moon Kyu

AU - Park, Joong Yeol

AU - Chung, Choon Hee

AU - Min, Kyung Wan

AU - Sung, Yeon Ah

AU - Park, Jeong Hyun

AU - Kim, Sung Jin

AU - Lee, Hyo Jung

AU - Park, Sung Woo

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N2 - Background: DA-1229 is a novel, potent and selective dipeptidyl peptidase-4 (DPP-IV) inhibitor that is orally bioavailable. We aimed to evaluate the optimal dose, efficacy and safety of DA-1229, in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise. Methods: We enrolled 158 patients (mean age, 53 years and a mean BMI, 25.6 kg/m2). The mean baseline fasting plasma glucose level, HbA1c and duration of diabetes were 8.28 mmol/L, 7.6% (60 mmol/mol) and 3.9 years, respectively. After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period, the subjects were randomized into one of four groups for a 12-week active treatment period: placebo, 2.5, 5 or 10 mg of DA-1229. Results: All three doses of DA-1229 significantly reduced HbA1c from baseline compared to the placebo group (-0.09 in the placebo group vs. -0.56, -0.66 and -0.61% in 2.5, 5 and 10-mg groups, respectively) but without any significant differences between the doses. Insulin secretory function, as assessed by homeostasis model assessment β-cell, the insulinogenic index, 2-h oral glucose tolerance test (OGTT) C-peptide and post-OGTT C-peptide area under the curve (AUC)0-2h, significantly improved with DA-1229 treatment. The incidence of adverse events was similar between the treatment groups and DA-1229 did not affect body weight or induce hypoglycaemic events. Conclusions: DA-1229 monotherapy (5 mg for 12 weeks) improved HbA1c, fasting plasma glucose level, OGTT results and β-cell function. This drug was well tolerated in Korean subjects with type 2 diabetes mellitus.

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KW - Dose-finding study

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