A multicenter, randomized, placebo-controlled, double-blind phase II trial evaluating the optimal dose, efficacy and safety of LC 15-0444 in patients with type 2 diabetes.
OBJECTIVE
The objective of this study was to evaluate the optimal dose, efficacy and safety of a novel dipeptidyl peptidase-4 (DPP-IV) inhibitor, LC15-0444, in Korean subjects with type 2 diabetes mellitus treated by diet and exercise.


METHODS
This study was a double-blind, randomized, multicenter and parallel-group, dose-range finding study. We enrolled 145 patients (91 men and 54 women) with a median age of 53 years and a median body mass index of 25.1 kg/m(2) . The median baseline fasting plasma glucose (FPG) was 8.1 mmol/l, the median HbA1c was 7.9% and the median time since the diagnosis of diabetes was 3 years. After 2 weeks of an exercise/diet programme followed by 2 weeks of a placebo period, the subjects were randomized to one of the four following groups for a 12-week active treatment period: placebo and 50, 100 or 200 mg of LC15-0444.


RESULTS
All three doses of LC15-0444 significantly reduced the HbA1c from baseline compared to the placebo group (-0.06 vs. -0.98, -0.74 and -0.78% in the placebo and 50, 100 and 200 mg groups, respectively), without a significant difference between the doses. Subjects with a higher baseline HbA1c (≥8.5%) had a greater reduction in HbA1c. Insulin secretory function, as assessed using homeostasis model assessment-beta cell, C-peptide and the insulinogenic index, improved significantly with LC15-0444 treatment. Insulin sensitivity, as assessed using homeostasis model assessment-insulin resistance, also improved significantly after 12 weeks of treatment. The 50 and 200 mg groups had significantly reduced total cholesterol and low-density lipoprotein cholesterol levels at 12 weeks compared to the placebo group. No dosage of LC15-0444 affected weight or waist circumference. The incidences of adverse events were similar in all study subjects.


CONCLUSIONS
LC15-0444 monotherapy (50 mg for 12 weeks) improved the HbA1c, FPG level, oral glucose tolerance test results, β-cell function and insulin sensitivity measures, and was well tolerated in Korean subjects with type 2 diabetes.
Rhee
E J
EJ
Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Lee
W Y
WY
Yoon
K H
KH
Yoo
S J
SJ
Lee
I K
IK
Baik
S H
SH
Kim
Y K
YK
Lee
M K
MK
Park
K S
KS
Park
J Y
JY
Cha
B S
BS
Lee
H W
HW
Min
K W
KW
Bae
H Y
HY
Kim
M J
MJ
Kim
J A
JA
Kim
D K
DK
Kim
S W
SW
D001786:Blood Glucose; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009930:Organic Chemicals / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010881:Piperidones; D010919:Placebos / Q000008:administration & dosage; D011743:Pyrimidines; D056910:Republic of Korea; D016896:Treatment Outcome
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D009930:Organic Chemicals; D010881:Piperidones; D010919:Placebos; D011743:Pyrimidines; C534891:LC15-0444