A Study of Combination Caplet With Loperamide Hydrochloride and Simethicone, and Imodium Express Tablets-lyophilizate Coadministered With Espumisan Capsule in Healthy Volunteers

Summary

The purpose of this study is to assess bioequivalence between a Combination caplet with loperamide hydrogen chloride (HCl) 2 milligram (mg) and simethicone 125 mg, and Imodium Express tablets-lyophilizate with loperamide HCl 2 mg (co-administered with Espumisan capsules with simethicone 40 mg), with respect to the single-dose pharmacokinetics of loperamide HCl. The maximum observed concentration (Cmax), and the area under the concentration-vs.-time curve until the last measurable concentration (AUC \[0-t\]) will be used to assess bioequivalence.

Timeline

Start

2019-12-05

Primary completion

2019-12-26

Completion

2019-12-26

Publications

• Background Federal Law N 323-FZ of 21.11.2011 (as amended on 02.07.2013.) "On the basis of public health protection in the Russian Federation";
• Background Federal law N 61-FZ "On Circulation of Medicines" of 12.04.2010 in the edition of Federal Laws (last revised on 29.12.2015 N 389-FZ);
• Background Order of the RF Ministry of Health of N 266 of 19.06.2003 "On approval of clinical practice rules in the Russian Federation";
• Background Order of the RF Ministry of Health of N200n of 01.04.2016 "On approval of rules for Good Clinical Practice";
• Background Good Clinical Practice. GOST R 52379-2005 (approved by Rostechregulirovanie Order N 232-st of 27.09.2005);
• Background Resolution of Government of the Russian Federation N 714 of 13 September 2010 "On approval of the standard rules of the compulsory life and health insurance of the patient involved in clinical trials of the drug" (in accordance with the Governmental regulation of the Russian Federation N 393 of 18 May 2011);
• Background Order No 986n of Ministry of Healthcare of Russian Federation "On approval of the Regulations on the Ethics Committee" dated 29.11.2012.
• Background Cottrell J, Koenig K, Perfekt R, Hofmann R; Loperamide-Simethicone Acute Diarrhoea Study Team. Comparison of Two Forms of Loperamide-Simeticone and a Probiotic Yeast (Saccharomyces boulardii) in the Treatment of Acute Diarrhoea in Adults: A Randomised Non-Inferiority Clinical Trial. Drugs R D. 2015 Dec;15(4):363-73. doi: 10.1007/s40268-015-0111-y.
• Background Hanauer SB, DuPont HL, Cooper KM, Laudadio C. Randomized, double-blind, placebo-controlled clinical trial of loperamide plus simethicone versus loperamide alone and simethicone alone in the treatment of acute diarrhea with gas-related abdominal discomfort. Curr Med Res Opin. 2007 May;23(5):1033-43. doi: 10.1185/030079907x182176.
• Background Kaplan MA, Prior MJ, Ash RR, McKonly KI, Helzner EC, Nelson EB. Loperamide-simethicone vs loperamide alone, simethicone alone, and placebo in the treatment of acute diarrhea with gas-related abdominal discomfort. A randomized controlled trial. Arch Fam Med. 1999 May-Jun;8(3):243-8. doi: 10.1001/archfami.8.3.243.
• Background Awouters F, Megens A, Verlinden M, Schuurkes J, Niemegeers C, Janssen PA. Loperamide. Survey of studies on mechanism of its antidiarrheal activity. Dig Dis Sci. 1993 Jun;38(6):977-95. doi: 10.1007/BF01295711.
• Background Awouters F, Niemegeers CJ, Janssen PA. Pharmacology of antidiarrheal drugs. Annu Rev Pharmacol Toxicol. 1983;23:279-301. doi: 10.1146/annurev.pa.23.040183.001431. No abstract available.
• Background Heykants J, Michiels M, Knaeps A, Brugmans J. Loperamide (R 18 553), a novel type of antidiarrheal agent. Part 5: the pharmacokinetics of loperamide in rats and man. Arzneimittelforschung. 1974 Oct;24(10):1649-53. No abstract available.
• Background Heel RC, Brogden RN, Speight TM, Avery GS. Loperamide: a review of its pharmacological properties and therapeutic efficacy in diarrhoea. Drugs. 1978 Jan;15(1):33-52. doi: 10.2165/00003495-197815010-00003.
• Background Kim KA, Chung J, Jung DH, Park JY. Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol. 2004 Oct;60(8):575-81. doi: 10.1007/s00228-004-0815-3. Epub 2004 Sep 8.
• Background Schinkel AH, Wagenaar E, Mol CA, van Deemter L. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest. 1996 Jun 1;97(11):2517-24. doi: 10.1172/JCI118699.
• Background Cummins CL, Jacobsen W, Benet LZ. Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J Pharmacol Exp Ther. 2002 Mar;300(3):1036-45. doi: 10.1124/jpet.300.3.1036.
• Background Mukwaya G, MacGregor T, Hoelscher D, Heming T, Legg D, Kavanaugh K, Johnson P, Sabo JP, McCallister S. Interaction of ritonavir-boosted tipranavir with loperamide does not result in loperamide-associated neurologic side effects in healthy volunteers. Antimicrob Agents Chemother. 2005 Dec;49(12):4903-10. doi: 10.1128/AAC.49.12.4903-4910.2005.
• Background Sadeque AJ, Wandel C, He H, Shah S, Wood AJ. Increased drug delivery to the brain by P-glycoprotein inhibition. Clin Pharmacol Ther. 2000 Sep;68(3):231-7. doi: 10.1067/mcp.2000.109156.
• Background Tayrouz Y, Ganssmann B, Ding R, Klingmann A, Aderjan R, Burhenne J, Haefeli WE, Mikus G. Ritonavir increases loperamide plasma concentrations without evidence for P-glycoprotein involvement. Clin Pharmacol Ther. 2001 Nov;70(5):405-14. doi: 10.1067/mcp.2001.119212.
• Background Brunton L Parker K, Blumenthal D, Buxton I. Treatment of Disorders of Bowel Motility and Water Flux; Anti-Emetics; Agents Used in Biliary and Pancreatic Disease.[Book Section] // Goodman and Gilman's The Pharmacological Basis of Therapeutics. - [s.l.]: McGraw-Hill Companies Inc., 2011. - 12.
• Background Meier M, Steuerwald R. Review of the therapeutic use of simethicone in gastroenterology. Schweiz Z GanzheitsMedizin. 2007;19: 380-7.
• Background Clinical Overview. Loperamide hydrochloride. Modification of the January 2008 Company Core Data Sheet for IMODIUM® capsules, orodispersible tablets and oral solution. Document No.: EDMS-ERI-20122913. Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (December 2010).
• Background China Periodic Safety Update Report 01 June 2011 to 13 August 2016 ; Loperamide hydrochloride, Loperamide oxide, Loperamide/simethicone. Global Medical Safety, Janssen Research & Development, LLC, 850 Ridgeview Drive, Horsham, Pennsylvania, 19044, USA. Doc No EDMS-ERI-125782448:1.0., 28 September 2016.
• Background Bioequivalence report for the Modified USP in vitro defoaming test using tablets and gel capsules. Report number NG-1681985; 09 Sep 2016.
• Background The United States Pharmacopeial Convention. USP Monographs: Simethicone. 2000;USP29-NF 24:1518.
• Background Report "On experimental comparative study of toxicity of drug product Loperamide+Simethicone, tablets 2 mg+125 mg, produced by Johnson & Johnson Consumer Inc., USA (finished product manufacturer) and Janssen Cilag S.p.A., Italy (release quality control) and registered alternative drug product". // Federal State Budgetary Institution of Science "Scientific Centre of Biomedical Technologies of the Federal Medical and Biological Agency". Svetlye Gory - 2016.
• Background EMEA Guideline on the Investigation of Bioequivalence, January 2010, CPMP/EWP/QWP/1401/98.
• Background ICH Topic E 2 A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting, Step 5. June 1995 CPMP/ICH/377/95.
• Background McNeil Study Report 15-005. An Open label, Randomized, Crossover Study to Demonstrate Bioequivalence of the Proposed Marketing Loperamide-Simethicone Caplet (batch C-826-23E) to the Currently Marketed Imodium Advanced® Caplet, and to Evaluate the Effect of Food on the Pharmacokinetics of Loperamide from the Proposed Marketing Loperamide-Simethicone Caplet. Fort Washington, PA: McNeil Consumer & Specialty Pharmaceuticals; 2006. Internal DocID: R0019405, R0024847 and R0014025.
• Background McNeil Study Report 98-068. Bioequivalence between Loperamide-Simethicone Caplets and Imodium® Advanced Chewable Tablets. McNeil Consumer Healthcare. Study Number CPR-154. 1999. Internal DocID: R0043738 and R0005710.
• Background Johnson & Johnson Study Report IMO-01. Bioequivalence between Loperamide-Simethicone Caplets and Imodium™ Plus Chewable Tables. Shandon Clinic Study Number SC00699. 2000. Internal DocID: J0041892.

Drugs

Indications

No indication recorded.