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

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.

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 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.