PMID- 31173870
OWN - NLM
STAT- MEDLINE
DCOM- 20200106
LR  - 20221207
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 136
DP  - 2019 Aug 1
TI  - Single-dose escalation study of yogliptin in healthy Chinese volunteers.
PG  - 104950
LID - S0928-0987(19)30213-1 [pii]
LID - 10.1016/j.ejps.2019.06.004 [doi]
AB  - BACKGROUND: Yogliptin is a novel xanthine dipeptidyl peptidase-4 (DPP-4) 
      inhibitor targeting type 2 diabetes. After promising preclinical pharmacological 
      studies, the first human trial of yogliptin was designed. METHODS: A randomized, 
      double-blind, parallel, placebo-controlled phase I single-dose escalation study 
      was designed to evaluate the pharmacokinetics, pharmacodynamics, and tolerability 
      after single oral doses of yogliptin in healthy Chinese subjects. Healthy 
      subjects were assigned to nine cohorts, which received a single dose of yogliptin 
      at 2.5, 5, 10, 25, 50, 100, 200, 400, or 600 mg. Two subjects in each cohort 
      received placebo. Blood samples were collected before dosing and up to 192 h 
      afterwards. Urine samples were collected until 120 h after dosing. Plasma and 
      urine drug concentrations were determined using liquid chromatography coupled 
      with tandem mass spectrometry, and DPP-4 activity was measured using a 
      semi-quantitative, fluorescence-based kinetic assay. RESULTS: A total of 104 
      subjects were enrolled, 103 of whom completed the study (mean age, 25.3 years; 
      mean weight, 58.8 kg; mean BMI, 21.8 kg/m(2)). A total of 27 adverse events (AEs) 
      occurred in 25 of 86 yogliptin subjects (29.1%), and 3 AEs occurred in 3 of 18 
      placebo subjects (16.7%). Yogliptin was absorbed with a median time of maximum 
      observed concentration (T(max)) of 3.0 h and was eliminated slowly with a t(1/2) 
      of 25.45-43.84 h. The maximum observed concentration (C(max)) and area under the 
      curve (AUC) varied slightly more than dose-proportionally over the dose range 
      from 2.5 to 400 mg. The fraction of drug excreted in urine ranged from 8.39% to 
      24.77%. Mean DPP-4 inhibition at 24 h after dosing ranged from 97.7% to 99.5%, 
      and DPP-4 inhibition was >80% for 72 h at doses from 25 to 400 mg. DPP-4 
      inhibition was >80% for 1 week in the group receiving 400 mg. CONCLUSION: 
      Yogliptin was well tolerated in healthy subjects, with no dose-limiting toxicity 
      observed in the range from 2.5 to 600 mg. Yogliptin inhibited plasma DPP-4 
      activity for 72 h at single doses of 25-200 mg and for 1 week at 400 mg, 
      suggesting that once-weekly dosing of yogliptin is possible in type 2 diabetes 
      patients. TRIAL REGISTRATION: ChiCTR-IIR-17010311 (Chictr.org).
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Gou, Zhong-Ping
AU  - Gou ZP
AD  - Institute of Drug Clinical Trials, West China Hospital, Sichuan University, 
      Chengdu 610041, People's Republic of China.
FAU - Wang, Zhen-Lei
AU  - Wang ZL
AD  - Institute of Drug Clinical Trials, West China Hospital, Sichuan University, 
      Chengdu 610041, People's Republic of China.
FAU - Liang, Xiu-Fang
AU  - Liang XF
AD  - Institute of Drug Clinical Trials, West China Hospital, Sichuan University, 
      Chengdu 610041, People's Republic of China.
FAU - Zheng, Li
AU  - Zheng L
AD  - Institute of Drug Clinical Trials, West China Hospital, Sichuan University, 
      Chengdu 610041, People's Republic of China.
FAU - Wang, Ying
AU  - Wang Y
AD  - Institute of Drug Clinical Trials, West China Hospital, Sichuan University, 
      Chengdu 610041, People's Republic of China.
FAU - Feng, Ping
AU  - Feng P
AD  - Institute of Drug Clinical Trials, West China Hospital, Sichuan University, 
      Chengdu 610041, People's Republic of China. Electronic address: 
      fengping@wchscu.cn.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20190604
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - EC 3.4.14.5 (Dipeptidyl Peptidase 4)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - Asian People
MH  - Blood Glucose/drug effects
MH  - Cohort Studies
MH  - Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - Dipeptidyl Peptidase 4/metabolism
MH  - Dipeptidyl-Peptidase IV Inhibitors/*pharmacokinetics/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Hypoglycemic Agents/pharmacokinetics/therapeutic use
MH  - Male
OTO - NOTNLM
OT  - Dose escalation
OT  - Healthy subjects
OT  - Pharmacodynamic
OT  - Pharmacokinetics
OT  - Single dose
OT  - Tolerability
OT  - Yogliptin
EDAT- 2019/06/08 06:00
MHDA- 2020/01/07 06:00
CRDT- 2019/06/08 06:00
PHST- 2019/02/28 00:00 [received]
PHST- 2019/05/12 00:00 [revised]
PHST- 2019/06/03 00:00 [accepted]
PHST- 2019/06/08 06:00 [pubmed]
PHST- 2020/01/07 06:00 [medline]
PHST- 2019/06/08 06:00 [entrez]
AID - S0928-0987(19)30213-1 [pii]
AID - 10.1016/j.ejps.2019.06.004 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2019 Aug 1;136:104950. doi: 10.1016/j.ejps.2019.06.004. Epub 
      2019 Jun 4.