Single Dose Two-periods Crossover Bioequivalence Study of Darifenacin Tablets in Healthy Volunteers.
Information source: Center for Clinical Pharmacology Research Bdbeq S.A.
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Bioequivalency
Intervention: Darifenacin (Drug); Darifenacin (Drug)
Phase: Phase 1
Status: Not yet recruiting
Sponsored by: Center for Clinical Pharmacology Research Bdbeq S.A. Official(s) and/or principal investigator(s):
Francisco E. Estevez-Carrizo, MD, Study Director, Affiliation: Univerisity of Montevideo. Biomedical Science Center.Prudencio de Pena 2440, 11600 Montevideo. Uruguay
Susana Parrillo, M.D., Principal Investigator, Affiliation: Center for Clinical Pharmacology Research Bdbeq S.A., Br. Artigas 1632. c.p. 11600 Montevideo. Uruguay.
Overall contact:
Federico Santoro, MD, Phone: +541143794300, Email: santorof@elea.com
Summary
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.
Clinical Details
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.
Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label
Primary outcome: Extent of Absorption.Rate of Absorption
Secondary outcome: Time to peak concentration (tmax)Absorption Rate Constant(Ka) Elimination Rate Constant (Ke)
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
Minimum age: 18 Years.
Maximum age: 50 Years.
Gender(s): Both.
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.
Locations and Contacts
Federico Santoro, MD, Phone: +541143794300, Email: santorof@elea.com
Center for Clinical Pharmacology Research Bdbeq S.A.; Hospital Italiano de Montevideo.., Montevideo 11600, Uruguay; Not yet recruiting
Susana Parrillo, MD, Phone: +59824876288, Ext: 201, Email: sparrillo@bdbeq.com.uy
Mónica Cedrés, Pharm. B., Phone: +59824876288, Ext: 202, Email: mcedres@bdbeq.com.uy
Additional Information
Related publications: Skerjanec A. The clinical pharmacokinetics of darifenacin. Clin Pharmacokinet. 2006;45(4):325-50. Review.
Starting date: November 2010
Last updated: October 22, 2010
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