A reproduced combination of ivacaftor and lumacaftor, CFTR protein modulators. Ethical and pharmacokinetic aspects

Abstract

The lack of effective and affordable therapies for rare diseases is an important ethical issue. One example is cystic fibrosis (CF), a chronic, progressive disease characterized by an impaired function of all exocrine glands. The combination of ivacaftor and lumacaftor (CFTR potentiator and corrector) should lead to a sufficient level of protein on the cell surface and to an increase in its activity, thereby correcting the impaired function. Development of a generic drug containing ivacaftor and lumacaftor as active pharmaceutical substances will increase the availability of this medication and improve patient survival. To study comparative pharmacokinetics and bioequivalence of drugs containing ivacaftor and lumacaftor in healthy volunteers. It was conducted as an open-label, randomized, crossover bioequivalence study involving a single intake of the drug during each period under fed condition in healthy male and female volunteers. The conclusion about bioequivalence was made if 90% confidence interval for primary pharmacokinetic parameters (Cmax, AUC0-t) fell within the accepted bioequivalence limits of 80–125%. According to the results of the study, it was shown that the values of 90% CI of the geometric mean of the main pharmacokinetic parameters for ivacaftor and lumacaftor fall within the acceptance limits for bioequivalence. According to the applied criteria, the drugs are bioequivalent, which makes it possible to recommend the investigational drug to the Ministry of Health of the Russian Federation for obtaining the registration status.