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Jang, Cho, Km, Chung, Lim, Jang, and Yu: A Placebo-Controlled, Single and Multiple Dose Study to Investigate the Appropriate Parameters for Evaluation of Phannacodynamic Equivalence of Voglibose in Healthy Korean Volunteers
Original Article

J Korean Soc Clin Pharmacol Ther 2013;21(1):63-70.

Published online: 11 January 2013

DOI: https://doi.org/10.12793/jkscpt.2013.21.1.63

A Placebo-Controlled, Single and Multiple Dose Study to Investigate the Appropriate Parameters for Evaluation of Phannacodynamic Equivalence of Voglibose in Healthy Korean Volunteers

Kyungho Jang1, Sang-Heon Cho2, Jung-Ryul Km3, Jae-Yong Chung4, Kyoung Soo Lim1, In-Jin Jang1, Kyung-Sang Yu1

1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea

2Department of Clinical Pharmacology, Inha University School of Medicine & Hospital, Incheon, Korea

3Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Korea

4Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Korea

E-mail: ksyu@snu.ac.kr

Received 19 June 20131 July 2013       Accepted 1 July 2013

Copyright © 2013 Korean Society for Clinical Pharmacology and Therapeutics

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

Voglibose is an α-glucosidase inhibitor. The purpose of this study was to evaluate the pharmacodynamic characteristics of voglibose for determining the appropriate study design and parameters for a pharmacodynamic equivalence study of voglibose.

Methods:

This study consisted of two studies. The single dose study had an open and single sequence design. Nineteen subjects received placebo and then one tablet of voglibose on two consecutive days with sucrose. The multiple dose study was performed with the similar design, except that it was a multiple dose of the single dose study. Nine subjects who showed an effective response in the single dose study received placebo three times and then voglibose 4 times on two consecutive days. Serial blood samples for pharmacodynamic parameters were taken until 180 mins after each administration. The baseline adjusted maximum serum glucose level (Gmax) and area under the serum glucose level-time profiles were determined and compared.

Results:

In the single dose study, the difference in Gmax was -10.6 ± 28.7 mg/dL. The area under the serum glucose concentration-time curve (AUGC0-1h) of placebo and voglibose were 7825.0 ± 1145.3 mg • min/dL, 7907.5 ± 917.2 mg • min/dL, respectively. In the multiple dose study, the difference in Gmax was 46.6 ± 16.1 mg/dL. The AUGC0-1h of placebo and voglibose were 8138.6 ± 721.9 mg • min/dL and 6499.7 ± 447.2 mg • min/dL, respectively. The Gmax and AUGC0-1h of the multiple dose study was significantly different between placebo and voglibose in paired t-test.

Conclusion:

The differences in Gmax and AUGC0-1h are suitable for pharmacodynamic parameters to evaluate bioequivalence of voglibose.

Keywords: Voglibose, Pharmacodynamic, Equivalence, Diabetes

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Figure 1.
Mean (SD) serum glucose concentration-time curve after single administration of placebo and voglibose.
jkscpt-21-63f1.tif
Figure 2.
Mean (SD) serum glucose concentration-time curve after multiple administration of placebo and voglibose.
jkscpt-21-63f2.tif
Table 1.
Demographic data of subjects
Single administration (N=19) Multiple administration (N=9)
Age, years 24.7 ± 3.5 24.4 ± 4.4
Height, cm 176.0 ± 4.8 173.8 ± 3.0
Weight, kg 71.2 ± 11.6 66.6 ± 14.0

Data are presented as mean ± standard deviation (SD).

Table 2.
Pharmacodynamic parameters after single administration (N=19)
PD parameters Summary statistics P * v† P - V (P-V) / P (%) P-value ‡
AUGC§0-1h Mean ± SD 7825.0 ± 1145.3 7907.5 ± 917.2 -82.5 ± 885.5 -2.2 ± 12.5 0.7
CV (%) 14.6 11.6 -1073.6 -567.5
AUGC0-2h Mean ± SD 14136.2 ± 1778.6 14578.3 ± 1435.6 -442.1 ± 1154.6 -3.8 ± 9.0 0.1
CV (%) 12.6 9.9 -261.1 -235.4
AUGC0-3h Mean ± SD 18891.8 ± 1919.8 19769.0 ± 1409.6 -877.1 ± 1236.0 -5.1 ± 7.0 <0.05
CV (%) 10.2 7.1 -140.9 -136.3
Gmax∥ Mean ± SD 153.6 ± 22.4 151.7 ± 19.2 -10.6 ± 28.7 -16.3 ± 28.2 0.6
CV (%) 14.6 12.6 -271.2 -172.9

* P: Placebo. † V: Voglibose (0.3 mg). ‡ The paired t-test was performed between placebo and voglibose. § AUGC: Area under the serum glucose concentration-time curve after administration (mg·min/dL). ∥ Gmax: Maximum observed serum glucose concentration (mg/dL).

Table 3.
Pharmacodynamic parameters after multiple administration (N=9)
PD parameters Summary statistics P * V† P - V (P-V) / P (%) p-value ‡
AUGC§0-1h Mean ± SD 8133.6 ± 721.9 6499.7 ± 447.2 1638.8 ± 762.7 19.6 ± 8.7 0.0002
CV (%) 8.9 6.9 46.5 44.2
AUGC0-2h Mean ± SD 14634.3 ± 1081.5 12441.9 ± 805.8 2192.4 ± 1249.2 14.6 ± 7.8 0.0008
CV (%) 7.4 6.5 57.0 53.3
AUGC0-3h Mean ± SD 19432.0 ± 1187.8 17677.3 ± 873.8 1754.7 ± 1454.8 8.7 ± 6.8 0.0068
CV (%) 6.1 4.9 82.9 78.1
Gmax∥ Mean ± SD 157.7 ± 19.1 121.4 ± 10.7 46.6 ± 16.1 30.1 ± 7.3 0.0003
CV (%) 12.1 8.8 34.5 24.1

* P: Placebo. † V: Voglibose (0.3 mg). ‡ The paired t-test was performed between placebo and voglibose. § AUGC: Area under the serum glucose concentration-time curve after administration (mg·min/dL). ∥ Gmax: Maximum observed serum glucose concentration (mg/dL).

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