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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Consumer and Personal Products Worldwide ( McNeil AB )
ClinicalTrials.gov Identifier:
NCT01302093
First received: February 22, 2011
Last updated: July 6, 2012
Last verified: July 2012
  Purpose

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


Condition Intervention Phase
Antidiarrheals
Drug: Racecadotril Film-Coated Tablet (FCT)
Drug: Racecadotril Capsule
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration [ Time Frame: During 24 hours following 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)

  • Bioavailability [AUC(0-t)] [ Time Frame: During 24 hours post-dose ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Bioavailability Extrapolated to Infinity [AUC (0-∞)] [ Time Frame: 24 hours post-dose ] [ Designated as safety issue: No ]
    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-∞).

  • Time of Maximum Concentration [ Time Frame: During 24 hours post-dose ] [ Designated as safety issue: No ]
    The time at which maximum concentration is reached (Tmax)

  • Terminal Elimination Rate Constant [ Time Frame: During 24 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 24 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.


Enrollment: 40
Study Start Date: January 2011
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental Tablet
A single 100 mg dose of an experimental Racecadotril Film-Coated Tablet (FCT)
Drug: Racecadotril Film-Coated Tablet (FCT)
A single 100 mg dose of an experimental Racecadotril FCT administered orally with 240 ml of water, with a 7- day washout between visits
Other Name: Not yet marketed
Active Comparator: Marketed Capsule
A single 100 mg dose of a marketed Racecadotril capsule
Drug: Racecadotril Capsule
A single 100 mg dose of a marketed Racecadotril capsule administered orally with 240 ml of water, with a 7-day washout between visits
Other Name: Tiorfast®

Detailed Description:

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.

  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) 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01302093

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: NCT01302093     History of Changes
Other Study ID Numbers: RACDIR1001
Study First Received: February 22, 2011
Last Updated: July 6, 2012
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Acetorphan
Thiorphan
Antidiarrheals
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014