PMID- 37564986
OWN - NLM
STAT- MEDLINE
DCOM- 20230816
LR  - 20230816
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 14
DP  - 2023
TI  - Pharmacokinetics, pharmacodynamics, and safety of prandial oral insulin (N11005) 
      in healthy subjects.
PG  - 1172327
LID - 10.3389/fendo.2023.1172327 [doi]
LID - 1172327
AB  - AIMS: To verify whether the oral insulin N11005 is administered as a prandial 
      insulin by assessing the pharmacokinetics (PK), pharmacodynamics (PD), and safety 
      profiles of N11005 with a short-acting biosynthetic human insulin (Novolin R) as 
      reference. METHODS: This was a randomized, open-label, single-dose, crossover 
      hyperinsulinemic-euglycemic clamp study in healthy Chinese male subjects. A total 
      of 12 subjects were enrolled in the test (T) group (N11005, 300 IU, p.o.) and the 
      reference (R) group (Novolin R, 0.1 IU/Kg, i.h.) with a washout period of 14 
      days. All subjects were administered on the same day of the clamp study. Glucose 
      Infusion Rates (GIR), serum insulin, and C-peptide concentration were determined 
      during every 8-hour clamp cycle. Trial registration: Clinicaltrials.gov 
      identifier NCT04975022. RESULTS: After administration, the ratios of mean serum 
      C-peptide concentration to baseline concentration in both T and R groups were 
      lower than 50%, which confirmed the stability of the clamp platform. T group 
      (N11005) showed a more rapid onset of action (tGIR(10%max) approximately 11 min) and a 
      comparable duration of action to the R group, which was basically in line with 
      the characteristics of prandial insulins. No adverse events (AEs) occurred 
      throughout the study, which demonstrated that N11005 and Novolin R are safe and 
      well-tolerated. CONCLUSIONS: The PD profiles of the single-dose N11005 in the 
      human body are similar to those of prandial insulins, with an excellent safety 
      profile. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT04975022.
CI  - Copyright (c) 2023 Pan, Wang, Li, Chen, Zhuang, Zhou, Huang, Zhou, Lan, Wang, Wang, 
      Hong, Hao, Yang and Guo.
FAU - Pan, Qi
AU  - Pan Q
AD  - Department of Endocrinology, Beijing Hospital, National Center of Gerontology, 
      Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 
      China.
FAU - Wang, Xiaoxia
AU  - Wang X
AD  - Department of Endocrinology, Beijing Hospital, National Center of Gerontology, 
      Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 
      China.
FAU - Li, Wenjia
AU  - Li W
AD  - Sunshine Lake Pharma Co., Ltd., Dongguan, China.
FAU - Chen, Xiaofeng
AU  - Chen X
AD  - Sunshine Lake Pharma Co., Ltd., Dongguan, China.
FAU - Zhuang, Yulei
AU  - Zhuang Y
AD  - Sunshine Lake Pharma Co., Ltd., Dongguan, China.
FAU - Zhou, Qinghong
AU  - Zhou Q
AD  - Sunshine Lake Pharma Co., Ltd., Dongguan, China.
FAU - Huang, Yuhui
AU  - Huang Y
AD  - Sunshine Lake Pharma Co., Ltd., Dongguan, China.
FAU - Zhou, Yijie
AU  - Zhou Y
AD  - Sunshine Lake Pharma Co., Ltd., Dongguan, China.
FAU - Lan, Li
AU  - Lan L
AD  - Sunshine Lake Pharma Co., Ltd., Dongguan, China.
FAU - Wang, Zhijie
AU  - Wang Z
AD  - Sunshine Lake Pharma Co., Ltd., Dongguan, China.
FAU - Wang, Wenjia
AU  - Wang W
AD  - Sunshine Lake Pharma Co., Ltd., Dongguan, China.
FAU - Hong, Juan
AU  - Hong J
AD  - Sunshine Lake Pharma Co., Ltd., Dongguan, China.
FAU - Hao, Wei-Hua
AU  - Hao WH
AD  - INNOPHARMAX, INC., Taipei, Taiwan.
FAU - Yang, Yu-Tsai
AU  - Yang YT
AD  - INNOPHARMAX, INC., Taipei, Taiwan.
FAU - Guo, Lixin
AU  - Guo L
AD  - Department of Endocrinology, Beijing Hospital, National Center of Gerontology, 
      Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 
      China.
LA  - eng
SI  - ClinicalTrials.gov/NCT04975022
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230726
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (C-Peptide)
RN  - 0 (Insulin)
SB  - IM
MH  - Humans
MH  - Male
MH  - C-Peptide
MH  - Glucose Clamp Technique
MH  - Healthy Volunteers
MH  - *Insulin/pharmacokinetics
MH  - Cross-Over Studies
PMC - PMC10411801
OTO - NOTNLM
OT  - healthy subjects
OT  - oral insulin
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - safety
COIS- Authors WL, XC, YLZ, QZ, YH, YJZ, LL, ZW, WW, and JH were employed by the company 
      Sunshine Lake Pharma Co., Ltd. Authors W-HH and Y-TY were employed by the company 
      INNOPHARMAX, INC. The authors declare that this study received funding from 
      Sunshine Lake Pharma Co., Ltd. The funder had the following involvement in the 
      study: experiment development, data research, statistical support, and animal 
      studies. W.H., and Y.Y. from INNOPHARMAX, INC. also contributed to animal 
      studies. The remaining authors declare that the research was conducted in the 
      absence of any commercial or financial relationships that could be construed as a 
      potential conflict of interest.
EDAT- 2023/08/11 06:43
MHDA- 2023/08/14 06:43
PMCR- 2023/01/01
CRDT- 2023/08/11 04:08
PHST- 2023/02/23 00:00 [received]
PHST- 2023/07/03 00:00 [accepted]
PHST- 2023/08/14 06:43 [medline]
PHST- 2023/08/11 06:43 [pubmed]
PHST- 2023/08/11 04:08 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2023.1172327 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2023 Jul 26;14:1172327. doi: 
      10.3389/fendo.2023.1172327. eCollection 2023.