Bioequivalence Between a Racecadotril Capsule and Film-Coated Tablet (FCT) to Treat Diarrhea in Adults

Study Overview
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Brief Summary
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This study is designed to assess bioequivalence between two products used for treatment of acute diarrhea.

Detailed Description
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The study will be a single dose, randomized, two-way crossover study in 40 healthy subjects, with equal numbers of males and females (minimum of 18 of either gender). Drop-outs will not be replaced. The two doses of medication given in the study (a single dose in each of the two study periods) will be separated by a washout period of at least 7 calendar days. In each study period, twenty (20) blood samples for pharmacokinetic analysis and, for the first 8 male and 8 female subjects included in the study (total of 16 subjects), seven (7) blood samples for pharmacodynamic analysis will be taken over 24 hours. Blood samples will be centrifuged and concentrations of thiorphan in plasma will be measured using a validated chromatographic assay. Pharmacokinetic parameters will be calculated from plasma concentration data. The rate and extent of absorption of the formulations will be compared.

Official Title
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A Two-Way Crossover, Open-Label, Single-Dose, Fasting, Bioequivalence Study of Racecadotril 100 mg FCT Versus Tiorfast® 100 mg Capsules, in Normal, Healthy, Non-Smoking Male and Female Subjects

Conditions
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Antidiarrheals

Intervention / Treatment
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* Drug: Racecadotril Film-Coated Tablet (FCT)
* Drug: Racecadotril Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects (equal numbers of males and females) - Volunteers aged of at least 18 years but not older than 55 years - Subjects will have a Body Mass Index (BMI) greater than or equal to 18.5 and below 30 kg/m2; and a total body weight >50 kg - Non- or ex-smokers; an ex-smoker being defined as someone who completely stopped smoking for at least 12 months before day 1 of this study. - Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance - Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, biochemistry, ECG and urinalysis) - Has signed and dated the informed consent document, indicating that the subject has been informed of all pertinent aspects of the study - Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures Exclusion Criteria: Seated pulse rate below 45 bpm or higher than 90 bpm at screening Seated blood pressure below 90/60 mmHg or higher than 140/90 mmHg at screening Relationship to persons involved directly with the conduct of the study (i.e., principal investigator; sub-investigators; study coordinators; other study personnel; employees or contractors of the sponsor or Johnson & Johnson subsidiaries; and the families of each) Females who are pregnant or are lactating Females of childbearing potential or males with a female partner of childbearing potential who refuse to use an acceptable contraceptive regimen throughout the entire duration of the study History of significant hypersensitivity to racecadotril or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs Use of certain drugs/medications within protocol-specified timeframes Medical history or condition that may, per protocol or in the opinion of the investigator, adversely affect the safety of the study subject or compromise study results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Tablet<br>A single 100 mg dose of an experimental Racecadotril Film-Coated Tablet (FCT) | Drug: Racecadotril Film-Coated Tablet (FCT)<br>* A single 100 mg dose of an experimental Racecadotril FCT administered orally with 240 ml of water, with a 7- day washout between visits<br>* Other names: Not yet marketed;|
| Active Comparator: Marketed Capsule<br>A single 100 mg dose of a marketed Racecadotril capsule | Drug: Racecadotril Capsule<br>* A single 100 mg dose of a marketed Racecadotril capsule administered orally with 240 ml of water, with a 7-day washout between visits<br>* Other names: Tiorfast®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration | Maximum Observed Plasma Concentration (Cmax), which is the maximum (peak) concentration (amount of drug) measurable in blood plasma after a dose is administered, measured in nanograms/milliliter (ng/mL) | During 24 hours following drug administration | 
| Bioavailability [AUC(0-t)] | Bioavailability [AUC(0-t)] is a measure of how much of the drug reaches the person's bloodstream within a given period of time for the body to use. The extent of product bioavailability is estimated by the area under the blood concentration vs time curve. The Area Under the Curve (AUC) is calculated by plotting the drug's blood levels on a graph at different times during the set period. The area under this curve reflects the amount of drug exposure in the set time period, calculated as hour * nanograms (ng) per milliliter (mL). | During 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioavailability Extrapolated to Infinity [AUC (0-∞)] | Bioavailability Extrapolated to Infinity [AUC (0-∞)] is a calculated measure of how much of the drug will ever reach the person's bloodstream for the body to use. AUC (0-∞) stands for the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (forever). It is obtained from calculating AUC (0-t) plus AUC (t-∞). | 24 hours post-dose | 
| Time of Maximum Concentration | The time at which maximum concentration is reached (Tmax) | During 24 hours post-dose | 
| Terminal Elimination Rate Constant | The Terminal Elimination Rate Constant (Lamda z) is the time required to eliminate half the administered dose | During 24 hours post-dose | 
| Terminal Phase Plasma Half-Life | Terminal phase plasma half-life (t ½) is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, rather than the time required to eliminate half the administered dose. | During 24 hours post-dose |