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  • Confirmation of bioequivalence of Vasoclean-Darnitsa, coated tablets, and Liprimar®, film-coated tablets: results of a randomized crossover replicated clinical trial in healthy volunteers

Confirmation of bioequivalence of Vasoclean-Darnitsa, coated tablets, and Liprimar®, film-coated tablets: results of a randomized crossover replicated clinical trial in healthy volunteers

25 квітня 2019
898
Artysh B.
Doroshenko A.
Sabko V.
Sotnychenko N.M.
Ключові слова :
bioequivalence,
generic,
healthy volunteers,
reference drug,
tablets,
аторвастатин
Резюме

The aim was to prove the bioequivalence of the test drug product Vasoclean-Darnitsa, atorvastatin 20 mg coated tablets, manufactured by PrJSC «Pharmaceutical Firm «Darnitsa» (Ukraine) and the reference drug product Liprimar®, atorvastatin 20 mg film-coated tablets, manufactured by Pfizer Manufacturing Deutschland GmbH (Germany) in a comparative randomized four-period two-sequence (TRTR/RTRT) crossover clinical trial in healthy volunteers. Materials and methods. Male volunteers took in the fasting condition a single 20 mg atorvastatin dose of the test and reference drugs (80 mg of atorvastatin during the whole study). Blood samples were taken within 48 hours. Quantitative determination of atorvastatin in blood plasma of the volunteers was performed using ultra-performance liquid chromatography with tandem mass selective detection. Results. Data from 37 healthy volunteers were included in the analysis of pharmacokinetics. For Vasoclean-Darnitsa and Liprimar®, mean atorvastatin Cmax values were 6.739±4.276 and 7.172±4.053 ng/mL, respectively, and corresponding mean AUC0–t values were 31.873±28.789 and 29.279±19.311 ng ‧ h/mL, respectively. The ranges of 90% confidence intervals of geometric mean ratio for Cmax (81.15–102.66%) and AUC0–t (94.09–111.09%) for Vasoclean-Darnitsa and Liprimar® meet prespecified acceptance criteria (80.00–125.00%). Suspected adverse reactions were observed in 5 volunteers and were considered to be non-serious. Conclusions. The bioequivalence of Vasoclean-Darnitsa, 20 mg atorvastatin coated tablets, and the reference drug product Liprimar®, 20 mg ator­vastatin film-coated tablets, was proven. Both drugs were well-tolerated following a single dose oral administration in the fasting state.

Published: 24.04.2019

References:

  • Verkhovna Rada Ukrainy (1996) Zakon Ukrainy vid 04.04.1996 r. «Pro likarski zasoby» (https://zakon.rada.gov.ua/laws/show/123/96-%D0%B2%D1%80).
  • Volosovets A.O. (2015) Osoblyvosti vplyvu patofiziolohichnykh ta medyko-sotsialnykh faktoriv ryzyku na chas vynyknennia mozkovoho ishemichnoho insultu: Zb. nauk. prats spivrobitnykiv NMAPO imeni P.L. Shupyka, 24(3): 82–91.
  • 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 MOZ Ukrainy 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 MOZ Ukrainy 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).
  • MOZ Ukrainy (2015) Nakaz MOZ Ukrainy vid 27.08.2015 r. № 549 «Pro provedennia klinichnoho vyprobuvannia likarskoho zasobu ta zatverdzhennia suttievoi popravky» (https://zakon.rada.gov.ua/rada/show/v0549282-15).
  • ST-N MOZU 42-6.0:2008 (2009) Nastanova «Likarski zasoby. Nalezhna laboratorna praktyka». Kyiv, 48 s.
  • ST-N MOZU 42-7.0:2008 (2009) Nastanova «Likarski zasoby. Nalezhna klinichna praktyka». Kyiv, 48 s.
  • ST-N MOZU 42-7.1:2014 (2014) Nastanova «Likarski zasoby. Doslidzhennia bioekvivalentnosti». Zatverdzheno nakazom MOZ Ukrainy vid 13.06.2014 r. № 396.
  • ST-N MOZU 42-7.2:2018 (2018) Nastanova «Likarski zasoby. Doslidzhennia bioekvivalentnosti». 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.
  • Kotlęga D., Gołąb-Janowska M., Meller A. et al. (2019) Beneficial effects of pre-stroke statins use in cardioembolic stroke patients with atrial fibrillation: a hospital-based retrospective analysis. Arch. Med. Sci., 15(2): 385–392.
  • 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).
  • 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.
  • Roth B.D. (2002) The discovery and development of atorvastatin, a potent novel hypolipidemic agent. Progress in Medicinal Chemistry, 1–22.
  • WHO TRS N 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.
  • Zhong P., Wu D., Ye X. et al. (2017) Secondary prevention of major cerebrovascular events with seven different statins: a multi-treatment meta-analysis. Drug Des. Devel. Ther., 11: 2517–2526.

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