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This study is designed to compare the pharmacokinetics of four products used for treatment of acute diarrhea.
The study will be a single dose, randomized, four -way, four-sequence crossover study in 24 healthy subjects, with equal numbers of males and females (minimum of 10 of either gender). Subjects who drop out will not be replaced. The four doses of medication given in the study (a single dose in each of the four study periods) will be separated by a washout period of at least 7 calendar days. In each study period, 17 blood samples for pharmacokinetic analysis will be taken over 12 hours. Blood samples will be centrifuged and concentrations of thiorphan (the active metabolite) in plasma will be measured using a validated chromatographic assay. Pharmacokinetic parameters will be calculated from plasma concentration data.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FCT | Experimental | A single 2 x100 mg dose of an experimental Racecadotril Film-coated tablet (FCT) administered orally with 240 ml of water, with a 7- day washout between visits. |
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| RPB | Experimental | A single 2 x100 mg dose of an experimental Racecadotril Powder Blend administered orally with 240 ml of water, with a 7- day washout between visits. |
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| TFT | Active Comparator | A single 2 x 100 mg dose of a marketed Tiorfast® capsule administered orally with 240 ml of water, with a 7-day washout between visits. |
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| TFR | Active Comparator | A single 175 mg dose of a marketed Tiorfanor® 175 mg FCT administered orally with 240 ml of water, with a 7-day washout between visits. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Racecadotril | Drug | Film-coated tablet |
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| 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) | Pre-dose and 0.25, 0.5, 0.75, 1, 1.25 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours post drug administration |
| AUC(0-t) | AUC(0-t) is the area under the plasma concentration verses time curve from start of drug administration until the time of the last measurable plasma concentration, calculated as hour*nanograms (ng) per milliliter (mL). | Pre-dose and 0.25, 0.5, 0.75, 1, 1.25 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours post drug administration |
| AUC(0-∞) | AUC (0-∞) is the area under the plasma concentration-vs.-time curve from start of drug administration until infinity. | Pre-dose and 0.25, 0.5, 0.75, 1, 1.25 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours post drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Time of Maximum Concentration | The time at which maximum concentration is reached (Tmax) | During 12 hours post-dose |
| Terminal Elimination Rate Constant | The Terminal Elimination Rate Constant (Lamda z) is the time required to eliminate half the administered dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Elisabeth Kruse, PhD | McNeil AB | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Algorithme Pharma Inc. | Mount Royal | Quebec | H3P 3P1 | Canada |
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| ID | Term |
|---|---|
| D003967 | Diarrhea |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C049331 | racecadotril |
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| Racecadotril | Drug | Racecadotril Powder Blend |
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| Racecadotril | Drug | Marketed Capsule |
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| Racecadotril | Drug | Marketed Film-coated Tablet |
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| During 12 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 12 hours post-dose |
| Lag Time | The time delay between drug administration and the quantification of absorption | During 12 hours post-dose |