Study to Compare the Pharmacokinetics Profiles of Four Racecadotril Products - Full Text View

Purpose

This study is designed to compare the pharmacokinetics of four products used for treatment of acute diarrhea.

Condition	Intervention	Phase
Diarrhea	Drug: Racecadotril	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Single Blind (Investigator) Primary Purpose: Basic Science
Official Title:	An Open-Label, Fasting, Crossover, Single-Dose Pharmacokinetic Study of Four Formulations of Racecadotril

Resource links provided by NLM:

MedlinePlus related topics: Diarrhea

U.S. FDA Resources

Further study details as provided by Johnson & Johnson Consumer and Personal Products Worldwide:

Primary Outcome Measures:

Maximum Observed Plasma Concentration [ Time Frame: 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 ] [ Designated as safety issue: No ]
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)
AUC(0-t) [ Time Frame: 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 ] [ Designated as safety issue: No ]
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).
AUC(0-∞) [ Time Frame: 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 ] [ Designated as safety issue: No ]
AUC (0-∞) is the area under the plasma concentration-vs.-time curve from start of drug administration until infinity.

Secondary Outcome Measures:

Time of Maximum Concentration [ Time Frame: During 12 hours post-dose ] [ Designated as safety issue: No ]
The time at which maximum concentration is reached (Tmax)
Terminal Elimination Rate Constant [ Time Frame: During 12 hours post-dose ] [ Designated as safety issue: No ]
The Terminal Elimination Rate Constant (Lamda z) is the time required to eliminate half the administered dose
Terminal Phase Plasma Half-Life [ Time Frame: During 12 hours post-dose ] [ Designated as safety issue: No ]
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.
Lag Time [ Time Frame: During 12 hours post-dose ] [ Designated as safety issue: No ]
The time delay between drug administration and the quantification of absorption

Enrollment:	24
Study Start Date:	December 2011
Study Completion Date:	December 2011
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: FCT 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.	Drug: Racecadotril Film-coated tablet Other Name: Not yet marketed
Experimental: RPB 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.	Drug: Racecadotril Racecadotril Powder Blend Other Name: Not yet marketed
Active Comparator: TFT 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.	Drug: Racecadotril Marketed Capsule Other Name: Tiorfast®
Active Comparator: TFR 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.	Drug: Racecadotril Marketed Film-coated Tablet Other Name: Tiorfanor®

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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) within protocol-specified parameters.
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 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 and blood pressure within protocol-specified parameters.
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01476683

Locations

Canada, Quebec
Algorithme Pharma Inc.
Mount-Royal, Quebec, Canada, H3P 3P1

Sponsors and Collaborators

McNeil AB

Investigators

Study Director:

Elisabeth Kruse, PhD

McNeil AB

More Information

No publications provided

Responsible Party:	Johnson & Johnson Consumer and Personal Products Worldwide ( McNeil AB )
ClinicalTrials.gov Identifier:	NCT01476683 History of Changes
Other Study ID Numbers:	RACDIR1002
Study First Received:	November 17, 2011
Last Updated:	July 6, 2012
Health Authority:	Canada: Health Canada

Keywords provided by Johnson & Johnson Consumer and Personal Products Worldwide:

Antidiarrheals

Additional relevant MeSH terms:

Diarrhea
Signs and Symptoms, Digestive
Signs and Symptoms
Acetorphan
Thiorphan
Antidiarrheals

Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013