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HealthyPhase 1NCT04186936

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

A Phase 1 study testing Combination Caplet with Loperamide HCl and Simethicone, Loperamide HCl and Simethicone in people with Healthy, run by McNeil AB at 1 site in Russia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Combination Caplet with Loperamide HCl and Simethicone, Loperamide HCl and Simethicone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteRussia
Study dates
5 Dec 2019to 26 Dec 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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)

Trial locations and contacts

1 site in 1 country.

Russia1 site
  • "Scientific and Research centre Eco-safety" Limited Liability Company

    Saint Petersburg, 196143

Other trials in Russia

About this study

Official title: An Open-label, Randomized, Fasting, Two-period, Single-dose, Crossover Study to Assess Bioequivalence Between a Combination Caplet With Loperamide Hydrochloride and Simethicone (Janssen-Cilag, France), and Imodium® Express Tablets-lyophilizate (Janssen-Cilag, France) Coadministered With Espumisan® Capsule (Berlin-Chemie AG, Germany), in Healthy Volunteers

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.

Conditions
Healthy
Being tested
Combination Caplet with Loperamide HCl and Simethicone, Loperamide HCl, Simethicone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Combination Caplet with Loperamide HCl and SimethiconeDrug

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

  • Loperamide HClDrug

    Also called Imodium Express

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

  • SimethiconeDrug

    Also called Espumisan

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

Study groups in NCT04186936
Study groupRoleWhat they receive
Treatment Sequence ABExperimentalParticipants 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.
Receives: Drug: Combination Caplet with Loperamide HCl and Simethicone; Drug: Loperamide HCl; Drug: Simethicone
Treatment Sequence BAExperimentalParticipants 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.
Receives: Drug: Combination Caplet with Loperamide HCl and Simethicone; Drug: Loperamide HCl; Drug: Simethicone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Observed Concentration (Cmax)

    Cmax is the maximum observed concentration.

    Measured: Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose

  2. Area Under the Plasma Concentration-tme Curve From Time Zero to Time 't' (AUC[0-t])

    AUC(0-t) is the area under the plasma concentration-time curve from time zero to time 't' (Time t is the time of the last measurable plasma concentration [Clast]).

    Measured: Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose

Secondary outcomes (10)
  1. Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity])

    AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z); wherein AUC(0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed measurable concentration, and lambda(z) is elimination rate constant.

    Measured: Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose

  2. Area Under the Plasma Concentration-time Curve Extrapolated from Last Measurable Concentration to Infinite Time (AUCextrap)

    AUC(extrap) is the area under the plasma concentration-time curve extrapolated from last measurable concentration to infinite time.

    Measured: Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose

  3. Time to Reach Maximum Observed Concentration (Tmax)

    Tmax is defined as time from investigational product administration to occurrence of Cmax.

    Measured: Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose

  4. Elimination Rate Constant (Lambda[z])

    Lambda (z) is the apparent terminal elimination rate constant, estimated by linear regression using the terminal logarithmic (log)-linear phase of the log-transformed concentration versus time data.

    Measured: Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose

  5. Elimination Half-Life (t1/2)

    The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).

    Measured: Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose

  6. Number of Participants with Adverse Events (AEs)

    An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

    Measured: Up to 31 days

  7. Number of Participants with Adverse Events by Severity

    The severity of AEs will be assessed by the Investigator or medically qualified individual using the following general categorical descriptors: a). Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with participant's usual function or normal everyday activities; b). Moderate: Sufficient discomfort is present to cause interference to some extent with participant's usual function or normal everyday activity; c). Severe: Extreme distress, causing significant impairment of functioning or incapacitation; interferes significantly with participants usual function; prevents normal everyday activities.

    Measured: Up to 31 days

  8. Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)

    An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Treatment-emergent events between administration of study drug up to 17 days that are absent before treatment or that worsened relative to pre-treatment state.

    Measured: Up to 17 days

  9. Number of Participants with Clinically Significant Change from Baseline in Vital Signs

    Number of participants with clinically significant change from baseline in vital signs (blood pressure and heart rate) will be reported.

    Measured: Up to 31 days

  10. Number of Participants with Clinically Significant Change from Baseline in Laboratory Abnormalities

    Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count etc.), chemistry (sodium, potassium, calcium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein, glucose, creatinine and cholesterol etc.) and urine (glucose, protein, blood, ketones, nitrites, leucocyte esterase, microscopic analysis etc.).

    Measured: Up to 31 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Dec 2019
  2. Study start5 Dec 2019
  3. Primary completion26 Dec 2019
  4. Study completion26 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04186936
Sponsor's protocol ID
CO-161213141338-DHCT
Other IDs
CO-161213141338-DHCT
Status last verified
Sep 2020
First submitted
3 Dec 2019
Last updated
10 Sep 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Johnson \& Johnson Consumer Inc. has an agreement with the Yale Open Data Access (YODA) Project to serve as the independent review panel for evaluation of requests for clinical study reports and participant level data from investigators and physicians for scientific research that will advance medical knowledge and public health. Requests for access to the study data can be submitted through the YODA Project site at http://yoda.yale.edu.

Publications

  • 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";

  • 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);

  • Order of the RF Ministry of Health of N 266 of 19.06.2003 "On approval of clinical practice rules in the Russian Federation";

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

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

  • 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);

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

  • 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.

    PubMed 26541878
  • 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.

    PubMed 17519069
  • 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.

    PubMed 10333820
  • 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.

    PubMed 8508715
  • 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.

    PubMed 6307123
  • 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.

    PubMed 4479779
  • 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.

    PubMed 342229
  • 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.

    PubMed 15365656

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Combination Caplet with Loperamide HCl and Simethicone, Loperamide HCl and Simethicone in people with Healthy, run by McNeil AB at 1 site in Russia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Concentration (Cmax) (time frame: Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04186936, which also lists 32 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2020.

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