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

NCT ID: NCT04186936

Last Updated: 2020-09-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-12-05

Study Completion Date

2019-12-26

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Healthy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment Sequence AB

Participants will receive Test Product A (single dose of 2 caplets \[Combination caplet with loperamide hydrocloride \[HCl\] 2 milligram \[mg\] + simethicone 125 mg\]) orally on Day 1 followed by Reference Product B (single dose of 2 Imodium Express tablets-lyophilizate \[2\*2 mg loperamide HCl\] + 6 Espumisan capsules \[6\*40 mg simethicone\]) orally on Day 13. A washout period of at least 7 days will be maintained between each treatment.

Group Type EXPERIMENTAL

Combination Caplet with Loperamide HCl and Simethicone

Intervention Type DRUG

Participants will receive combination caplet with loperamide HCl 2 mg and simethicone 125 mg as Test product A per assigned treatment sequence.

Loperamide HCl

Intervention Type DRUG

Participants will receive loperamide HCl 2 mg tablet-lyophilizate orally as part of Reference product B per assigned treatment sequence.

Simethicone

Intervention Type DRUG

Participants will receive Simethicone 40 mg capsule orally as part of Reference product B per assigned treatment sequence.

Treatment Sequence BA

Participants will receive Reference product B orally on Days 1 followed by Test product A orally on Day 13. A washout period of at least 7 days will be maintained between each treatment.

Group Type EXPERIMENTAL

Combination Caplet with Loperamide HCl and Simethicone

Intervention Type DRUG

Participants will receive combination caplet with loperamide HCl 2 mg and simethicone 125 mg as Test product A per assigned treatment sequence.

Loperamide HCl

Intervention Type DRUG

Participants will receive loperamide HCl 2 mg tablet-lyophilizate orally as part of Reference product B per assigned treatment sequence.

Simethicone

Intervention Type DRUG

Participants will receive Simethicone 40 mg capsule orally as part of Reference product B per assigned treatment sequence.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Combination Caplet with Loperamide HCl and Simethicone

Participants will receive combination caplet with loperamide HCl 2 mg and simethicone 125 mg as Test product A per assigned treatment sequence.

Intervention Type DRUG

Loperamide HCl

Participants will receive loperamide HCl 2 mg tablet-lyophilizate orally as part of Reference product B per assigned treatment sequence.

Intervention Type DRUG

Simethicone

Participants will receive Simethicone 40 mg capsule orally as part of Reference product B per assigned treatment sequence.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Imodium Express Espumisan

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Body Mass Index (BMI) between 18.5 and 30.0 kilogram per meter (kg/m\^2), inclusive, and a total body weight greater than or equal to (\>=) 50.0 kilogram (kg)
* Females of childbearing potential must have a negative urine pregnancy test at the baseline visit
* Male or non-pregnant, non-lactating female agree to the contraceptive requirements (including female partner's use of a highly effective method of birth control for at least 3 months before the study, during the study and for 30 days after the last dose of investigational product)
* A personally signed and dated informed consent document before participating in any study specific procedures, indicating that the participant has been informed of all pertinent aspects of the study
* Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures specified in the protocol example: swallowing of tablets

Exclusion Criteria

* Use of medications, prescription medication and/or over-the-counter medication including vitamins, herbal supplements, medicinal plants (example supplements containing garlic extract), and topical preparations of drugs that are systemically absorbed (example steroids and non-steroid anti-inflammatory drugs) within two weeks prior to dosing
* Use of St. John's wort (Hypericum perforatum) within 30 days prior to the first dose of study medication
* Abnormal results of laboratory and instrumental methods of examinations, including electrocardiogram (ECG)
* Females with a positive pregnancy test and/or are breast-feeding
* Females, currently using hormonal contraceptives (including use less than 2 months prior to enrollment)
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

McNeil AB

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Konstantin Anatolyevich Zacharov

Role: PRINCIPAL_INVESTIGATOR

McNeil AB

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

"Scientific and Research centre Eco-safety" Limited Liability Company

Saint Petersburg, , Russia

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Russia

References

Explore related publications, articles, or registry entries linked to this study.

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";

Reference Type 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);

Reference Type 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";

Reference Type BACKGROUND

Order of the RF Ministry of Health of N200n of 01.04.2016 "On approval of rules for Good Clinical Practice";

Reference Type BACKGROUND

Good Clinical Practice. GOST R 52379-2005 (approved by Rostechregulirovanie Order N 232-st of 27.09.2005);

Reference Type 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);

Reference Type BACKGROUND

Order No 986n of Ministry of Healthcare of Russian Federation "On approval of the Regulations on the Ethics Committee" dated 29.11.2012.

Reference Type 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.

Reference Type BACKGROUND
PMID: 26541878 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17519069 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10333820 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8508715 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6307123 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 4479779 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 342229 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15365656 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8647944 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11861813 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16304151 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11014404 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11719726 (View on PubMed)

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.

Reference Type BACKGROUND

Meier M, Steuerwald R. Review of the therapeutic use of simethicone in gastroenterology. Schweiz Z GanzheitsMedizin. 2007;19: 380-7.

Reference Type 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).

Reference Type 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.

Reference Type BACKGROUND

Bioequivalence report for the Modified USP in vitro defoaming test using tablets and gel capsules. Report number NG-1681985; 09 Sep 2016.

Reference Type BACKGROUND

The United States Pharmacopeial Convention. USP Monographs: Simethicone. 2000;USP29-NF 24:1518.

Reference Type 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.

Reference Type BACKGROUND

EMEA Guideline on the Investigation of Bioequivalence, January 2010, CPMP/EWP/QWP/1401/98.

Reference Type BACKGROUND

ICH Topic E 2 A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting, Step 5. June 1995 CPMP/ICH/377/95.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type BACKGROUND

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CO-161213141338-DHCT

Identifier Type: OTHER

Identifier Source: secondary_id

CO-161213141338-DHCT

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.