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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
NONE
Enrollment
24
Single dose 7.5 mg tablets of darifenacin
Single dose 7.5 mg tablets of Darifenacin
Center for Clinical Pharmacology Research (CCPR) Bdbeq S.A. Hospital Italiano.
Montevideo, Montevideo Department, Uruguay
Extent of absorption
Extent of absorption will be measured using the area under the plasma concentration of darifenacin vs time from time 0 to the last sample point (AUC0-t) and from time 0 to infinity (AUC0-inf.
Time frame: 72 hours
Rate of absorption
Rate of abosorption will be measured using peak concentration of darifenacin (Cmax)taken from the concentration vs. time curve.
Time frame: 72
Time to peak concentration (tmax)
Tmax is the time elapsed from ingestion of darifenacin tablets to plasma peak concentration (Cmax)
Time frame: 72
Elimination rate constant (Ke)
The elimination rate constant is the fractional rate of drug disappearance form the peripheral compartement, measured in the log-linear elimination phase.
Time frame: 72 hours
Elimination Half-life (t1/2e)
t1/2e is the time in which the concentration in the log-linear elimination phase drops by half.
Time frame: 72 hours
Systemic clearance (Cls)
Cls is the amount of plasma volume units that are totally cleared of the drug in the unit of time.
Time frame: 72 hours
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