PMID- 36526947
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230224
IS  - 1869-6953 (Print)
IS  - 1869-6961 (Electronic)
IS  - 1869-6961 (Linking)
VI  - 14
IP  - 2
DP  - 2023 Feb
TI  - Bioequivalence Evaluation in Healthy Volunteers: New Generic Formulations of 
      Sitagliptin and Sitagliptin-Metformin Fixed-Dose Combination Compared with the 
      Originator Products.
PG  - 347-362
LID - 10.1007/s13300-022-01349-2 [doi]
AB  - INTRODUCTION: Three studies compared the bioequivalence (BE) of new generic 
      tablet formulations of sitagliptin (100 mg; fasting) and the fixed-dose 
      combination (FDC) of sitagliptin/metformin (50/850 mg, 50/1000 mg; both fed) in 
      healthy volunteers with the same tablet strengths of the reference products 
      Januvia and Janumet. METHODS: The study design was open-label, single-dose, 
      randomized with two-way crossover periods. Blood sampling was performed for 
      72/48 h in the sitagliptin/FDC studies, respectively. Primary pharmacokinetic 
      (PK) parameters for sitagliptin and metformin were area under the plasma 
      concentration-time curve from time 0 to last timepoint of measurable 
      concentration (AUC(0-t)) and maximum plasma concentration (C(max)). Test (T) and 
      reference (R) formulations proved bioequivalent if 90% confidence interval (CI) 
      of geometric least-squares mean ratio for AUC(0-t) and C(max) were within BE 
      acceptance range of 80.00-125.00%. Safety evaluations included vital signs, 
      clinical laboratory tests, and adverse events (AEs). RESULTS: Treated/evaluable 
      volunteers for BE per study were: 30/28 (sitagliptin 100 mg), 26/25 (FDC 
      50/850 mg), and 26/24 (FDC 50/1000 mg). The 90% CI of the geometric means of T/R 
      ratios for primary PK parameters were within predefined BE limits: CI for 
      AUC(0-t) and C(max) were 95.83-100.37% and 91.85-109.56% (sitagliptin 100 mg); 
      100.84-103.69% and 93.44-105.10% (FDC 50/850 mg), and 101.26-105.20% and 
      98.71-112.89% (FDC 50/1000 mg); respective values for metformin were 
      94.23-101.89% and 91.66-99.38% (FDC 50/850 mg) and 98.45-104.89% and 
      96.79-105.62% (FDC 50/1000 mg). All AEs were nonserious, transient, and mostly 
      mild. Safety evaluations did not reveal any relevant difference between T and R 
      formulations. CONCLUSIONS: The new generic tablet formulations of sitagliptin 
      100 mg and the FDCs sitagliptin/metformin 50/850 mg and 50/1000 mg demonstrated 
      bioequivalence to originator reference products. Therefore, the new products are 
      expected to provide efficacy and tolerability similar to those of the reference 
      products in the treatment of patients with type 2 diabetes (T2D). TRIAL 
      REGISTRATION: EudraCT EU Clinical Trials Registry (2014-005437-31); 
      ClinicalTrials.gov Registry (NCT05549570 and NCT05549583, both retrospectively 
      registered on 20 September 2022).
CI  - (c) 2022. The Author(s).
FAU - Schnaars, Yvonne
AU  - Schnaars Y
AUID- ORCID: 0000-0002-3306-5025
AD  - Merck Healthcare KGaA, Frankfurter Str. 250, Post Code F135 /001, 64293, 
      Darmstadt, Germany. yvonne.schnaars@merckgroup.com.
FAU - Gaikwad, Sumedh
AU  - Gaikwad S
AD  - Merck Healthcare KGaA, Frankfurter Str. 250, Post Code F135 /001, 64293, 
      Darmstadt, Germany.
FAU - Gottwald-Hostalek, Ulrike
AU  - Gottwald-Hostalek U
AD  - Merck Healthcare KGaA, Frankfurter Str. 250, Post Code F135 /001, 64293, 
      Darmstadt, Germany.
FAU - Uhl, Wolfgang
AU  - Uhl W
AD  - Merck Healthcare KGaA, Frankfurter Str. 250, Post Code F135 /001, 64293, 
      Darmstadt, Germany.
FAU - Ribot, Olga
AU  - Ribot O
AD  - Galenicum Health S.L.U., Barcelona, Spain.
FAU - Varanasi, Kanthikiran V S
AU  - Varanasi KVS
AD  - Galenicum Health India Pvt. Ltd, Hyderabad, India.
FAU - Rodriguez, Laura
AU  - Rodriguez L
AD  - Galenicum Health S.L.U., Barcelona, Spain.
FAU - Torrejon, Javier
AU  - Torrejon J
AD  - Galenicum Health S.L.U., Barcelona, Spain.
FAU - Gomez, Luis
AU  - Gomez L
AD  - Galenicum Health S.L.U., Barcelona, Spain.
LA  - eng
SI  - ClinicalTrials.gov/NCT05549570
SI  - ClinicalTrials.gov/NCT05549583
PT  - Journal Article
DEP - 20221216
PL  - United States
TA  - Diabetes Ther
JT  - Diabetes therapy : research, treatment and education of diabetes and related 
      disorders
JID - 101539025
PMC - PMC9943811
OTO - NOTNLM
OT  - Bioequivalence
OT  - Diabetes
OT  - Dipeptidyl peptidase-4 inhibitor
OT  - Fixed-dose combination
OT  - Metformin
OT  - Pharmacokinetics
OT  - Single-pill combination
OT  - Sitagliptin
EDAT- 2022/12/17 06:00
MHDA- 2022/12/17 06:01
PMCR- 2022/12/16
CRDT- 2022/12/16 23:44
PHST- 2022/10/21 00:00 [received]
PHST- 2022/11/24 00:00 [accepted]
PHST- 2022/12/17 06:00 [pubmed]
PHST- 2022/12/17 06:01 [medline]
PHST- 2022/12/16 23:44 [entrez]
PHST- 2022/12/16 00:00 [pmc-release]
AID - 10.1007/s13300-022-01349-2 [pii]
AID - 1349 [pii]
AID - 10.1007/s13300-022-01349-2 [doi]
PST - ppublish
SO  - Diabetes Ther. 2023 Feb;14(2):347-362. doi: 10.1007/s13300-022-01349-2. Epub 2022 
      Dec 16.