Bioequivalence of the medicinal product Preventor (rosuvastatin), film-coated tablets, to the reference medicinal product Crestor® (rosuvastatin), film-coated tablets, in a randomized crossover clinical trial in healthy volunteers

September 3, 2019
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Resume

The aim is to prove the bioequivalence of the test medicinal product Preventor, 20 mg rosuvastatin film-coated tablets, manufactured by PrJSC «Pharmaceutical Firm «Darnitsa» (Ukraine) and the reference medicinal product Crestor®, 20 mg rosuvastatin film-coated tablets, manufactured by «AstraZeneca UK Limited» (United Kingdom) in a comparative randomized four-period two-sequence (TRTR/RTRT) crossover clinical trial in healthy volunteers. Materials and methods. Male and female volunteers took in the fasting condition a single 20 mg rosuvastatin dose of the test or reference medicinal product (80 mg of rosuvastatin during the whole study). Blood samples were taken within 72 hours. Quantitative determination of rosuvastatin in blood plasma of the volunteers was performed using high-performance liquid chromatography with tandem mass selective detection. Results. Data from 30 healthy volunteers were included in the analysis of pharmacokinetics. For Preventor and Crestor®, mean rosuvastatin Cmax values were 17.055±12.555 and 16.968±11.192 ng/mL, respectively, and corresponding mean AUC0–t values were 128.745±67.100 and 130.877±68.342 ng‧h/mL, respectively. The ranges of 90% confidence intervals of geometric mean ratio for Cmax (91.19–105.53%) and AUC0–t (93.67–104.79%) for Preventor and Crestor® meet prespecified acceptance criteria (80.00–125.00%). Six adverse events were reported in 4 volunteers. Adverse events were unlikely or doubtly related to study treatment and were considered to be non-serious. Conclusions. The bioequivalence of generic medicinal product Preventor, 20 mg rosuvastatin film-coated tablets, and the refe­rence medicinal product Crestor®, 20 mg rosuvastatin film-coated tablets, was proven. Both drugs were well-tolerated following a single dose (within each period) oral administration in the fasting state.

Published: 03.09.2019
References:

  • Verkhovna Rada Ukrainy (1996) Zakon Ukrainy vid 04.04.1996 r. № 123/96-VR «Pro likarski zasoby» (https://zakon.rada.gov.ua/laws/show/123/96-%D0%B2%D1%80).
  • Vsemirnaya meditsinskaya assotsiatsiya (1964) Helsinskaya deklaratsiya Vsemirnoy meditsinskoy assotsiatsii. Eticheskie printsipyi dlya meditsinskih issledovaniy s privlecheniem cheloveka v kachestve sub’ekta ispyitaniya (s izmeneniyami).
  • Handziuk V.A., Diachuk D.D., Kondratiuk N.Iu. (2017) Dynamika zakhvoriuvanosti ta smertnosti vnaslidok khvorob systemy krovoobihu v Ukraini (rehionalnyi aspekt). Visn. probl. biol. med., 2: 319–323.
  • Zhukova N.A., Libina V.V., Kudris I.V., Padalko N.N. (2013) Validatsiya bioanaliticheskogo metoda. Metod. rekomend. GETs MZ Ukrainyi, Kiev, 35 s.
  • MOZ Ukrainy (2005) Nakaz vid 26.08.2005 r. № 426 «Pro zatverdzhennia Poriadku provedennia ekspertyzy reiestratsiinykh materialiv na likarski zasoby, shcho podaiutsia na derzhavnu reiestratsiiu (perereiestratsiiu), a takozh ekspertyzy materialiv pro vnesennia zmin do reiestratsiinykh materialiv protiahom dii reiestratsiinoho posvidchennia» (https://zakon.rada.gov.ua/laws/show/z1069-05).
  • MOZ Ukrainy (2009) Nakaz vid 23.09.2009 r. № 690 «Pro zatverdzhennia Poriadku provedennia klinichnykh vyprobuvan likarskykh zasobiv ta ekspertyzy materialiv klinichnykh vyprobuvan i Typovoho polozhennia pro komisii z pytan etyky» (https://zakon.rada.gov.ua/laws/show/z1010-09).
  • ST-N MOZU 42-6.0:2008 (2009) Likarski zasoby. Nalezhna laboratorna praktyka: Nastanova. Kyiv, 48 s.
  • ST-N MOZU 42-7.0:2008 (2009) Likarski zasoby. Nalezhna klinichna praktyka: Nastanova. Kyiv, 48 s.
  • ST-N MOZU 42-7.1:2016 (2017) Likarski zasoby. Doslidzhennia bioekvivalentnosti: Nastanova. Zatverdzheno nakazom MOZ Ukrainy vid 12.01.2017 r. № 22.
  • ST-N MOZU 42-7.2:2018 (2018) Likarski zasoby. Doslidzhennia bioekvivalentnosti: Nastanova. Zatverdzheno nakazom MOZ Ukrainy vid 02.11.2018 r. № 2014.
  • Terenda N.O. (2015) Smertnist vid sertsevo-sudynnykh zakhvoriuvan yak derzhavna problema. Visn. nauk. doslidzh., 4: 11–13.
  • EMA (2010) Guideline on the investigation of bioequivalence. CPMP/EWP/QWP/1401/98/Rev.1/Corr (https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-bioequivalence-rev1_en.pdf).
  • EMA (2015) Guideline on bioanalytical method validation. EMEA/CHMP/192217/2009 Rev. 1 Corr 2 (https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-bioanalytical-method-validation_en.pdf).
  • EMA (2016) Guideline for good clinical practice E6(R2). EMA/CHMP/ICH/135/199 (https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-6-r1-guideline-good-clinical-practice-step-5_en.pdf).
  • Endo A. (2010) A historical perspective on the discovery of statins. Proc. Jpn. Acad. Ser. B. Phys. Biol. Sci., 86(5): 484–493.
  • European Commission (2013) Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use (http://ec.europa.eu/health/files/eudralex/vol-10/ctqa_v11.pdf, http://ec.europa.eu/health/files/clinicaltrials/2012_07/summary/2012_07_summary_en.pdf).
  • Fedder D.O., Koro C.E., L’Italien G.J. (2002) New National Cholesterol Education Program III guidelines for primary prevention lipid-lowering drug therapy: projected impact on the size, sex, and age distribution of the treatment-eligible population. Circulation, 105(2): 152–156.
  • Grundy S., Becker D., Luther C. (2002) Third Report of the National Cholesterol Education Program (NCEP). Detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Final report. Natl. Heart Lung Blood Inst., 106: 3143.
  • ICH (2016) Integrated addendum to ICH E6(R1): Guideline for good clinical practice E6(R2) (https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__Step_4_2016_1109.pdf).
  • Jellinger P.S., Handelsman Y., Rosenblit P.D. et al. (2017) American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr. Pract., 23(Suppl. 2): 1–87.
  • Lewis S.J. (2011) Lipid-lowering therapy: who can benefit? Vasc. Health Risk Manag., 7: 525–534.
  • McFarland A.J., Anoopkumar-Dukie S., Arora D.S. et al. (2014) Molecular mechanisms underlying the effects of statins in the central nervous system. Int. J. Mol. Sci., 15(11): 20607–20637.
  • Morris P.B., Ballantyne C.M., Birtcher K.K. et al. (2014) Review of clinical practice guidelines for the management of LDL-related risk. J. Am. Coll. Cardiol., 64(2): 196–206.
  • OECD (2004) The OECD principles of good laboratory practice (GLP).
  • Pappa E., Rizos C.V., Filippatos T.D., Elisaf M.S. (2019) Emerging fixed-dose combination treatments for hyperlipidemia. J. Cardiovasc. Pharmacol. Ther., 24(4): 315–322.
  • Reiner Z., Catapano A.L., De Backer G. et al. (2011) ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur. Heart J., 32(14): 1769–1818.
  • Roger V.L., Go A.S., Lloyd-Jones D.M. et al. (2011) Heart disease and stroke statistics–2011 update: a report from the American Heart Association. Circulation, 123(4): e18–e209.
  • WHO TRS № 937 (2006) Additional guidance for organization performing in vivo bioequivalence studies. Annex 9.
  • Wood D., De Backer G., Faergeman O. et al. (1998) Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. Atherosclerosis, 140: 199–270.