PMID- 36264446
OWN - NLM
STAT- MEDLINE
DCOM- 20221129
LR  - 20221129
IS  - 1179-6901 (Electronic)
IS  - 1174-5886 (Print)
IS  - 1174-5886 (Linking)
VI  - 22
IP  - 4
DP  - 2022 Dec
TI  - Chinese- and French-Manufactured Immediate-Release Glucophage((R)) Bioequivalence: 
      A Randomized, Open-Label, Crossover Study.
PG  - 301-309
LID - 10.1007/s40268-022-00405-3 [doi]
AB  - OBJECTIVE: We aimed to assess the bioequivalence, safety, and tolerability of 
      Chinese- and French-manufactured Glucophage((R)) immediate-release (GIR) tablets 
      under fasted and fed conditions in healthy volunteers. A bioequivalence study was 
      proposed to support the manufacturing transfer. METHODS: This was an open-label, 
      randomized, two-period, two-sequence, crossover study. Subjects were randomly 
      assigned to receive the test product (one 500 mg GIR tablet manufactured in 
      China) or reference product (one 500 mg GIR tablet manufactured in France). The 
      primary study endpoint was the area under the plasma concentration-time curve 
      from time zero to the last sampling time (AUC(t)) and maximum observed 
      concentration (C(max)). RESULTS: In total, 96 subjects were screened and 44 
      subjects were randomly assigned to treatment (fasted group, 26 subjects; fed 
      group, 18 subjects). All 44 subjects received the study drug, completed the 
      study, and were included in the pharmacokinetic (PK) and safety analysis sets. 
      Under fasted or fed conditions, the mean AUC(t) and C(max) (primary PK 
      parameters) were comparable between the test and reference products. Point 
      estimates for both parameters were close to 100% and the corresponding 90% 
      confidence intervals were within the specified 80-125% bioequivalence boundary. 
      There were no hypoglycemia-related adverse events (AEs) in either treatment 
      group. All AEs in the present study were mild in severity. CONCLUSIONS: 
      Bioequivalence between the test and reference GIR tablets was demonstrated under 
      fasted and fed conditions and both were safe and well tolerated. CLINICAL TRIALS 
      REGISTRATION: This study was registered at ClinicalTrials.gov under the 
      identifying number NCT03393208.
CI  - (c) 2022. The Author(s).
FAU - Hu, Chaoying
AU  - Hu C
AUID- ORCID: 0000-0002-0116-4387
AD  - Department of Pharmacy, Phase I Clinical Trial Center, Xuanwu Hospital of Capital 
      Medical University, National Clinical Research Center for Geriatric Diseases, No. 
      45 Changchun Street, Xicheng District, Beijing, China.
FAU - Gao, Dan
AU  - Gao D
AD  - Department of Pharmacy, Phase I Clinical Trial Center, Xuanwu Hospital of Capital 
      Medical University, National Clinical Research Center for Geriatric Diseases, No. 
      45 Changchun Street, Xicheng District, Beijing, China.
FAU - Li, Dandan
AU  - Li D
AD  - Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd (an affiliate of Merck KGaA), 
      Beijing, China.
FAU - Zhou, Dongli
AU  - Zhou D
AD  - Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd (an affiliate of Merck KGaA), 
      Beijing, China.
FAU - Zhang, Lan
AU  - Zhang L
AUID- ORCID: 0000-0002-5220-3171
AD  - Department of Pharmacy, Phase I Clinical Trial Center, Xuanwu Hospital of Capital 
      Medical University, National Clinical Research Center for Geriatric Diseases, No. 
      45 Changchun Street, Xicheng District, Beijing, China. xwzhanglan@126.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT03393208
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20221020
PL  - New Zealand
TA  - Drugs R D
JT  - Drugs in R&D
JID - 100883647
RN  - 9100L32L2N (Metformin)
RN  - 0 (Tablets)
SB  - IM
MH  - Humans
MH  - Cross-Over Studies
MH  - Therapeutic Equivalency
MH  - *Metformin
MH  - Area Under Curve
MH  - Tablets
MH  - China
MH  - Healthy Volunteers
MH  - Fasting
PMC - PMC9700552
COIS- Dandan Li and Dongli Zhou are employees of Merck Serono (Beijing) Pharmaceutical 
      R&D Co., Ltd, China, an affiliate of Merck KGaA. Chaoying Hu, Dan Gao, and Lan 
      Zhang report no conflicts of interest.
EDAT- 2022/10/21 06:00
MHDA- 2022/11/30 06:00
PMCR- 2022/10/20
CRDT- 2022/10/20 11:19
PHST- 2022/09/16 00:00 [accepted]
PHST- 2022/10/21 06:00 [pubmed]
PHST- 2022/11/30 06:00 [medline]
PHST- 2022/10/20 11:19 [entrez]
PHST- 2022/10/20 00:00 [pmc-release]
AID - 10.1007/s40268-022-00405-3 [pii]
AID - 405 [pii]
AID - 10.1007/s40268-022-00405-3 [doi]
PST - ppublish
SO  - Drugs R D. 2022 Dec;22(4):301-309. doi: 10.1007/s40268-022-00405-3. Epub 2022 Oct 
      20.