Single Dose Bioequivalence Study of Darifenacin Tablets 7.5 mg in Fed Healthy Volunteers.

NCT ID: NCT01229280

Last Updated: 2010-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-12-31

Study Completion Date

2011-02-28

Brief Summary

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The proposed study was designed as a randomized two-sequence, two period crossover trial to assess the bioequivalence, pharmacokinetic profiling and safety of a brand generic formulation of darifenacin \[Darisec(R) 7.5 mg\] vs. the innovator \[Enablex(R)7.5 mg\]in healthy volunteers in postprandial state.

Detailed Description

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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. A bioequivalence study will be performed to validate pharmaceutical development before introducing the product in the market.

The purpose in this study is to evaluate the relative bioavailability, pharmacokinetic profiling and safety of a brand generic formulation of darifenacin \[Darisec(R) 7.5 mg\] vs. the innovator \[Enablex(R) 7.5 mg\]in 24 healthy uruguayan volunteers after a high fat breakfast of 1000 calories (50% fat, 35% carbohydrates, and 15% proteins)to establish their average bioequivalence.

The bioequivalence will be evaluated using:

* The Area Under the Curve (AUC),
* The peak plasma concentration (Cmax).

The pharmacokinetic characteristics of the drug formulations will be described calculating:

* The time to peak concentration (Tmax)
* The elimination constant (Ke)
* The elimination half-life (t1/2e)
* The systemic clearance (Cls)

Safety will be evaluated recording:

* Reported adverse events
* Vital signs (blood pressure, heart rate, body temperature)
* 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 requirements:

* Mean AUCt/AUCr and 90% confidence interval within 0.80-1.25
* Mean Cmaxt/Cmaxr and 90% confidence interval within 0.80-1.25

Pharmacokinetic profiling will be evaluated by describing the pharmacokinetic characteristics of both drug in adequate two-way tables.

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

Conditions

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Bioequivalency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Blinding Strategy

NONE

Study Groups

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Darisec(R) 7.5 mg

Group Type EXPERIMENTAL

Darifenacin

Intervention Type DRUG

Single dose 7.5 mg tablets of darifenacin

Enablex(R) 7.5 mg

Group Type ACTIVE_COMPARATOR

Darifenacin

Intervention Type DRUG

Single dose 7.5 mg tablets of Darifenacin

Interventions

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Darifenacin

Single dose 7.5 mg tablets of darifenacin

Intervention Type DRUG

Darifenacin

Single dose 7.5 mg tablets of Darifenacin

Intervention Type DRUG

Other Intervention Names

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Muscarinic antagonist Cholinergic antagonist Cholinergic agent Darisec Muscarinec antagonist Cholinergic antagonist Cholinergic agent Enablex

Eligibility Criteria

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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 glaucoma, 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 drug 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 which 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 results.
* 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 (vitamins, herbal supplements, dietary supplements)within 2 weeks prior to dosing. Paracetamol and ibuprofen are acceptable.
* Participation in any clinical investigation within 12 weeks prior to dosing.
* Donation or loss of 400 ml or more of blood within 8 weeks prior to dosing.
* Significant illness within 2 weeks prior to dosing.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Laboratorio Elea Phoenix S.A.

INDUSTRY

Sponsor Role collaborator

Center for Clinical Pharmacology Research Bdbeq S.A.

OTHER

Sponsor Role lead

Responsible Party

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Center for Clinical Pharmacology Research Bdbeq S.A.

Principal Investigators

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Francisco E. Estevez-Carrizo, MD

Role: STUDY_DIRECTOR

Univerisity of Montevideo. Biomedical Science Center.Prudencio de Pena 2440, 11600 Montevideo. Uruguay

Susana Parrillo, M.D.

Role: PRINCIPAL_INVESTIGATOR

Center for Clinical Pharmacology Research Bdbeq S.A., Br. Artigas 1632. c.p. 11600 Montevideo. Uruguay.

Locations

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Center for Clinical Pharmacology Research (CCPR) Bdbeq S.A. Hospital Italiano.

Montevideo, Montevideo Department, Uruguay

Site Status

Countries

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Uruguay

Central Contacts

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Federico Santoro, MD

Role: CONTACT

+541143794300

Joanna Steimberg, MBA

Role: CONTACT

+541143794330

Facility Contacts

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Francisco E. Estevez-Carrizo, M.D.

Role: primary

+59824876288

Mónica Cedrés, Pharm. B.

Role: backup

+59824876288

References

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Skerjanec A. The clinical pharmacokinetics of darifenacin. Clin Pharmacokinet. 2006;45(4):325-50. doi: 10.2165/00003088-200645040-00001.

Reference Type BACKGROUND
PMID: 16584282 (View on PubMed)

Croom KF, Keating GM. Darifenacin: in the treatment of overactive bladder. Drugs Aging. 2004;21(13):885-92; discussion 893-4. doi: 10.2165/00002512-200421130-00005.

Reference Type BACKGROUND
PMID: 15493952 (View on PubMed)

Staskin DR. Overactive bladder in the elderly: a guide to pharmacological management. Drugs Aging. 2005;22(12):1013-28. doi: 10.2165/00002512-200522120-00003.

Reference Type BACKGROUND
PMID: 16363885 (View on PubMed)

Kerbusch T, Wahlby U, Milligan PA, Karlsson MO. Population pharmacokinetic modelling of darifenacin and its hydroxylated metabolite using pooled data, incorporating saturable first-pass metabolism, CYP2D6 genotype and formulation-dependent bioavailability. Br J Clin Pharmacol. 2003 Dec;56(6):639-52. doi: 10.1046/j.1365-2125.2003.01967.x.

Reference Type BACKGROUND
PMID: 14616424 (View on PubMed)

Dmochowski RR, Appell RA. Advancements in pharmacologic management of the overactive bladder. Urology. 2000 Dec 4;56(6 Suppl 1):41-9. doi: 10.1016/s0090-4295(00)01020-7.

Reference Type BACKGROUND
PMID: 11114562 (View on PubMed)

Other Identifiers

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BDBEQ_DFNLP/ELEA_010

Identifier Type: -

Identifier Source: org_study_id