Single Dose Two-periods Crossover Bioequivalence Study of Darifenacin Tablets in Healthy Volunteers.

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2010 by Center for Clinical Pharmacology Research Bdbeq S.A..
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
Laboratorio Elea S.A.C.I.F. y A.
Information provided by:
Center for Clinical Pharmacology Research Bdbeq S.A.
ClinicalTrials.gov Identifier:
NCT01227811
First received: October 18, 2010
Last updated: October 22, 2010
Last verified: October 2010
  Purpose

The present study was designed to assess the bioequivalence and pharmacokinetic profiling of a brand generic formulation of darifenacin [Darisec(R)]vs. the innovator [Enablex(R)]in healthy volunteers after a high fat breakfast.

The bioequivalence will be evaluated using:

  • the Area Under the Curve (AUC) and,
  • the peak plasma concentration (Cmax).

Safety will be evaluated recording:

  • vital signs
  • adverse events,
  • laboratory analysis.
  • EKG and chest XRays.

Bioequivalence will be claimed if the drugs comply with local regulatory requirement, eg.:

  • mean AUCt/AUCr and 90% confidence interval within 0.80-1.25
  • mean Cmaxt/Cmaxr and 90% confidence interval within 0.80-1.25.

Condition Intervention Phase
Bioequivalency
Drug: Darifenacin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Single Dose, Two-period, Crossover, Fed Bioequivalence Study of Darifenacin Extended Release Oral Formulation (Darisec(R) 15 mg) vs. Enablex(R) 15 mg in Healthy Volunteers.

Resource links provided by NLM:


Further study details as provided by Center for Clinical Pharmacology Research Bdbeq S.A.:

Primary Outcome Measures:
  • Extent of Absorption. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Extent of absorption will be measured using the area under plasma concentrations of darifenacin vs. time from time 0 to the last sample point (AUC0-t) and from time 0 to infinity (AUC0-inf).

  • Rate of Absorption [ Time Frame: 72 ] [ Designated as safety issue: No ]
    Rate of abosrption will be measured using the peak concentration of darifenacin (Cmax).


Secondary Outcome Measures:
  • Time to peak concentration (tmax) [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Is the time elapsed from ingestion of darifenacin tablets to plasma peak concentration.

  • Absorption Rate Constant(Ka) [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    The absorption rate constant is the fractional rate of drug disappearance from the intestinal tract, measured in the log-linear phase of drug absorption.

  • Elimination Rate Constant (Ke) [ Time Frame: 72 ] [ Designated as safety issue: No ]
    The elimiminaiton rate constant is the fractional rate of drug dissapearance from the peripheral compartment, measured in the log-linear phase of elimination.


Estimated Enrollment: 24
Study Start Date: November 2010
Estimated Study Completion Date: March 2011
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Enablex(R) 15 mg , single dose Drug: Darifenacin
Single oral dose Enablex(R) 15 mg
Experimental: Darifenacin 15 mg tablets, single dose Drug: Darifenacin
Single oral dose Darisec(R) 15.0 mg
Other Names:
  • Muscarinic Antagonists
  • Cholinergic Antagonists
  • Cholinergic Agents
  • Enablex
  • Darisec

Detailed Description:

Darifenacin is a muscarinic receptor antagonist drug used to treat overactive bladder. There is a new formulation of darifenacin extended release developed by an argentinian pharmaceutical company and, according to regional regulations, a bioequivalence study should be performed to put it in the market.

The purpose of this study is to evaluate the relative bioavailability and pharmacokinetic profiling of a brand generic formulation of darifenacin [Darisec(R) 15 mg] vs. the innovator [Enablex(R) 15 mg] in 24 healthy uruguayan volunteers after a high fat breakfast of 1000 calories (50% fat, 35% carbohydrates (sugar, flour, etc.) and 15& proteins) to establish their average bioequivalence.

The bioequivalence will be evaluated using outcome measures that will be described later.

The pharmacokinetic characteristics of the drugs will be described calculating:

  • the time to Cmax (Tmax)
  • the elimination constant (Ke),
  • the elimination half-life (t1/2e)and,
  • the systemic clearance (Cls.

Safety will be evaluated recording:

  • vital signs (blood pressure, heart rate, body temperature)
  • adverse events,
  • laboratory analysis (hemogram, hepatic enzymes, creatinine, sugar in blood,etc.).
  • EKG and chest XRays.

Bioequivalence will be claimed if the drugs comply with local and FDA regulatory requirement, eg.:

  • mean AUCt/AUCr and 90% confidence interval within 0.80-1.25
  • mean Cmaxt/Cmaxr and 90% confidence interval within 0.80-1.25.

Safety will be evaluated comparing incidences of adverse events/adverse effects for both products.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male or female subjects 18 to 50 years of age (inclusive)
  • In good health, as determined by lack of clinically significant abnormalities at screening as judged by the physician.
  • Female subjects are required to use a medically accepted method of hormonal contraception or abstinence throughout the entire study period and for one week after the study is completed.
  • Body mass index within the range of 18.5 and 29.9 kg/m2 and weight at least 45 kg.

Exclusion Criteria:

  • Known hypersensitivity or severe adverse event to darifenacin or similar drugs.
  • Urinary retention, narrow-angle glucoma, myasthenia gravis, severe hepatic impairment, severe ulcerative colitis, toxic megacolon.
  • Symptomatic hiatus hernia, erosive or symptomatic gastroesophageal reflux disease/heartburn (>2 days in a week), severe constipation, gastrointestinal obstructive disorder, and gastric retention.
  • Clinically significant cardiac abnormalities, fainting, low blood pressure upon standing, irregular heartbeats.
  • Acute or chronic bronchospastic disease (including asthma and Chronic Obstructive Pulmonary Disease).
  • Clinically significant drug allergy or history of atopic allergy (asthma, urticaria, eczematous dermatitis).
  • Smokers of more than 5 cigarettes a week.
  • Regular use of any drugs known to induce or inhibit hepatic drug metabolism (particularly those that affect CYP2D6) within 30 days prior to each study drug administration.
  • Any surgical or medical condition wich might significantly alter the absorption, distribution, metabolism or excretion of drugs which may jeopardize participation in the study.
  • Immunodeficiency diseases, including a positive HIV (Elisa or Western blot) test result.
  • Positive hepatitis B Surface antigen (HBsAg) or Hepatitis C test result.
  • Drug or alcohol abuse within the 6 months prior to dosing.
  • Use of prescription drugs within 1 month prior to dosing, or over-the-counter medication (vitamine, herbal supplements, dietary supplements) within 2 weeks prior to dosing. Paracetamol and ibuprofen are acceptable.
  • Participation in any clinical investigation within 4 weeks prior to dosing.
  • Donation or loss of 400 ml or more of blood within 2 months prior to dosing.
  • significant illness within 2 weeks prior to dosing.
  • Other protocol-defined inclusion/exclusion criteria may apply.
  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: NCT01227811

Contacts
Contact: Federico Santoro, MD +541143794300 santorof@elea.com
Contact: Joanna Steimberg, MBA +541143794330 steimbej@elea.com

Locations
Uruguay
Center for Clinical Pharmacology Research Bdbeq S.A.; Hospital Italiano de Montevideo.. Not yet recruiting
Montevideo, Uruguay, 11600
Contact: Susana Parrillo, MD    +59824876288 ext 201    sparrillo@bdbeq.com.uy   
Contact: Mónica Cedrés, Pharm. B.    +59824876288 ext 202    mcedres@bdbeq.com.uy   
Sponsors and Collaborators
Center for Clinical Pharmacology Research Bdbeq S.A.
Laboratorio Elea S.A.C.I.F. y A.
Investigators
Study Director: Francisco E. Estevez-Carrizo, MD Univerisity of Montevideo. Biomedical Science Center.Prudencio de Pena 2440, 11600 Montevideo. Uruguay
Principal Investigator: Susana Parrillo, M.D. Center for Clinical Pharmacology Research Bdbeq S.A., Br. Artigas 1632. c.p. 11600 Montevideo. Uruguay.
  More Information

Publications:
Responsible Party: Francisco E. Estevez-Carrizo, M.D. / Principal investigator., Center for Clinical Pharmacology Research Bdbeq S.A.
ClinicalTrials.gov Identifier: NCT01227811     History of Changes
Other Study ID Numbers: BDBEQ_DFNLP/ELEA_011
Study First Received: October 18, 2010
Last Updated: October 22, 2010
Health Authority: Uruguay: Comite de Etica

Keywords provided by Center for Clinical Pharmacology Research Bdbeq S.A.:
Darifenacin
Bioequivalence
Healthy volunteers
Postprandial

Additional relevant MeSH terms:
Muscarinic Antagonists
Darifenacin
Cholinergic Agents
Cholinergic Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014