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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Combination Caplet with Loperamide HCl and Simethicone
* Drug: Loperamide HCl
* Drug: Simethicone


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence AB<br>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. | Drug: Combination Caplet with Loperamide HCl and Simethicone<br>* Participants will receive combination caplet with loperamide HCl 2 mg and simethicone 125 mg as Test product A per assigned treatment sequence.<br>Drug: Loperamide HCl<br>* Participants will receive loperamide HCl 2 mg tablet-lyophilizate orally as part of Reference product B per assigned treatment sequence.<br>* Other names: Imodium Express;Drug: Simethicone<br>* Participants will receive Simethicone 40 mg capsule orally as part of Reference product B per assigned treatment sequence.<br>* Other names: Espumisan;|
| Experimental: Treatment Sequence BA<br>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. | Drug: Combination Caplet with Loperamide HCl and Simethicone<br>* Participants will receive combination caplet with loperamide HCl 2 mg and simethicone 125 mg as Test product A per assigned treatment sequence.<br>Drug: Loperamide HCl<br>* Participants will receive loperamide HCl 2 mg tablet-lyophilizate orally as part of Reference product B per assigned treatment sequence.<br>* Other names: Imodium Express;Drug: Simethicone<br>* Participants will receive Simethicone 40 mg capsule orally as part of Reference product B per assigned treatment sequence.<br>* Other names: Espumisan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) | Cmax is the maximum observed concentration. | Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose | 
| 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]). | Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose | 
| 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. | Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose | 
| Time to Reach Maximum Observed Concentration (Tmax) | Tmax is defined as time from investigational product administration to occurrence of Cmax. | Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose | 
| 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. | Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose | 
| 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). | Predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 24, 30, 36, 48, and 72 hours postdose | 
| 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. | Up to 31 days | 
| 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. | Up to 31 days | 
| 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. | Up to 17 days | 
| 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. | Up to 31 days | 
| 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.). | Up to 31 days |