Clinical trial NCT01227811: Single Dose Two-periods Crossover Bioequivalence Study of Darifenacin Tablets in Healthy Volunteers.
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Bioequivalency
Keywords: Darifenacin
Bioequivalence
Healthy volunteers
Postprandial
Lead sponsor: Center for Clinical Pharmacology Research Bdbeq S.A.
Sponsor class: OTHER
Collaborators: name: Laboratorio Elea Phoenix S.A.
First posted: 2010-10-25
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief 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.

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 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.

Primary outcomes:
measure: Extent of Absorption.
timeFrame: 72 hours
measure: Rate of Absorption
timeFrame: 72
Secondary outcomes:
measure: Time to peak concentration (tmax)
timeFrame: 72 hours
measure: Absorption Rate Constant(Ka)
timeFrame: 72 hours
measure: Elimination Rate Constant (Ke)
timeFrame: 72
Other outcomes:
Locations:
city: Montevideo
country: Uruguay
facility: Center for Clinical Pharmacology Research Bdbeq S.A.; Hospital Italiano de Montevideo..
Study officials:
affiliation: Univerisity of Montevideo. Biomedical Science Center.Prudencio de Pena 2440, 11600 Montevideo. Uruguay
name: Francisco E. Estevez-Carrizo, MD
role: STUDY_DIRECTOR
affiliation: Center for Clinical Pharmacology Research Bdbeq S.A., Br. Artigas 1632. c.p. 11600 Montevideo. Uruguay.
name: Susana Parrillo, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Skerjanec A. The clinical pharmacokinetics of darifenacin. Clin Pharmacokinet. 2006;45(4):325-50. doi: 10.2165/00003088-200645040-00001.