Exploration of suitable pharmacodynamic parameters for acarbose bioequivalence evaluation: A series of clinical trials with branded acarbose.
Br J Clin Pharmacol
; 86(11): 2225-2233, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32333407
ABSTRACT
AIMS:
To determine deficiencies in the Food and Drug Administration (FDA)'s guidance for assessing acarbose bioequivalence (BE) and to explore optimal pharmacodynamic (PD) metrics for better evaluation of acarbose BE.METHODS:
Three clinical trials with branded acarbose were conducted in healthy subjects, including a pilot study (Study I, n = 11, 50 and 100 mg), a 2×2 crossover BE study (Study II, n = 36, 100 mg) and a 4×4 Williams study (Study III, n = 16, 50/100/150 mg). Serum glucose concentrations were measured by the glucose oxidase method.RESULTS:
In Study I, compared with 50 mg acarbose, only 100 mg acarbose had a significantly lower Cmax0-4h than that of sucrose administration alone (7.96 ± 0.83 mmol/L vs 6.78 ± 1.02 mmol/L, P < .05). In Study II, the geometric mean ratios of the test formulation to the reference formulation (both formulations were the branded drug) for FDA PD metrics, ΔCmax0-4h and ΔAUC0-4h , were 0.903 and 0.776, respectively, and the 90% confidence intervals were 67.44-120.90 and 53.65-112.13, respectively. The geometric mean ratios (confidence interval) for possible optimal evaluation PD metrics (Cmax0-2h and AUC0-2h ) were 1.035 (94.23-112.68) and 0.982 (89.28-107.17), respectively. Further, Cmax0-2h and AUC0-2h also met the sensitivity requirements for BE evaluation in Study III.CONCLUSION:
Considering the mechanisms of action of acarbose, the PD effect was shown to be dose independent during the 2-4 hours postadministration of acarbose. Hence PD metrics based on the serum glucose concentration from 0 to 2 hours (Cmax0-2h and AUC0-2h ) are more sensitive than the FDA-recommended PD metrics for acarbose BE evaluation from 0-4 hours (ΔCmax0-4h and ΔAUC0-4h ). The trial has been registered at the Chinese Clinical Trial Registry (http//www.chictr.org.cn, ChiCTR1800015795, ChiCTR-IIR-17013918, ChiCTR-IIR-17011903). All subjects provided written informed consent before screening.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acarbose
Tipo de estudo:
Clinical_trials
/
Guideline
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Br J Clin Pharmacol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China