A Relative Bioavailability Study of Two Formulations of Topiramate 100 mg Coated Tablet in Healthy Male Volunteers, the Test Formulation Produced by Dr. Reddy's Laboratories Ltd. and the Reference Formulation (Topamax®) Marked by Janssen-Cilag Farmacêutica Ltda.
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Area under curve of plasma concentration of drug from the time 0 (zero) extrapolated to infinity (AUC0-inf)
Overview
Brief Summary
This study is prospective, open-label, randomized, crossover, single dose, with 02 treatments, 02 sequences and 02 periods. The volunteers received, in each period, the reference or the test formulation, according to the randomization list, under fasting conditions, in order to evaluate if the reference and test formulations are bioequivalent.
Detailed Description
This study is prospective, open-label, randomized, crossover, single dose, with 02 treatments, 02 seuqences and 02 periods. The objective is to confirm if two formulations of topiramate 100 mg, coated tablet, are bioequivalent, after oral, single-dose administration under fasting conditions. The test product is topiramate 100 mg produced by Dr. Reddy's Laboratories Ltd. and the reference product is Topamax® marketed by Janssen-Cilag Farmacêutica Ltda. Twenty-eight healthy male volunteers were evaluated. The volunteers received, in each period, the test or the reference formulation, according to the randomization list. In each period, blood samples are collected in the following times: 00:00 (prior to the administration of medication); 00:20; 00:40; 01:00; 01:30; 02:00; 02:30; 03:00; 03:30; 04:00; 05:00; 06:00; 08:00; 12:00; 16:00; 20:00; 24:00; 48:00; 72:00; 96:00; 120:00; 144:00; 168:00; 192:00. The comparative bioavailability of the two formulations was evaluated based in statistical comparisons of relevant pharmacokinetic parameters, obtained from data of drug concentrations in blood.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age between 18 and 50 years
- •Body mass index between 19 and 28,5 kg/m2
- •Good health conditions
- •Capable to understand the study's nature and aim, including risks and adverse effects and with intention to cooperate with the researcher and to act in compliance with requirements of the assay, this will be confirmed by the informed consent's signature
Exclusion Criteria
- •The volunteer has a known hypersensitivity to the study drug (topiramate) or to compounds chemically related
- •History or presence of hepatic or gastrointestinal illnesses, or other condition that interferes over the drug's absorption, distribution, excretion or metabolism
- •History of hepatic, renal, pulmonary, gastrointestinal, epileptic, hematologic or psychiatric illness; hypo or hypertension of any etiologic that needs pharmacologic treatment; has history or had myocardial infarction, angina and/or heart insufficiency
- •Non-recommended electrocardiographic findings, according to investigator criteria, for the study's participation
- •The results of the laboratory exams are out of the values considered as normal according to this protocol's rules, unless that they are considered as clinically irrelevant by the investigator
- •The volunteer is a smoker
- •The volunteer ingests more than 5 cups of coffee or tea a day
- •Has history of alcohol or drugs abuse
- •Use any regular drug within the 02 weeks that preceded the beginning of the treatment and the assessment date, or employed any drug that can interfere with the study within one week
- •The volunteer was hospitalized for any reason within 08 weeks of the beginning of this study's first period of treatment and the assessment date
Arms & Interventions
Test formulation
Test product: Topiramate 100 mg coated tablets produced by Dr. Reddy's Laboratories Ltd. in Period 1, followed by 28 days washout period during which no medication was administered; followed by reference product: Topamax® 100 mg coated tablets in Period 2
Intervention: Topiramate coated tablet (Drug)
Reference formulation
Topamax® 100 mg coated tablets marketed by Janssen-Cilag farmacêutica Ltda. in Period 1, followed by 28 days washout period during which no medication was administered; followed by test product: Topiramate 100 mg coated tablets produced by Dr. Reddy's Laboratories Ltd. in Period 2
Intervention: Topamax® coated tablet (Drug)
Outcomes
Primary Outcomes
Area under curve of plasma concentration of drug from the time 0 (zero) extrapolated to infinity (AUC0-inf)
Time Frame: Collection points from time 0 to 192 hours evaluated in two periods
Measurement obtained directly from the plasma concentration curve of drug against time (non-compartimental method). AUC0-inf is calculated from time 0 (prior to administration of medication) extrapolated to infinity, by formula AUC0-inf=AUClast +Clast/Kel, where Clast is the Last measurable concentration and Kel is the first order rate constant associated with the terminal portion of the curve.
Area under curve of plasma concentration of drug from time 0 (zero) from time t (last measurable concentration)
Time Frame: Collection points from time 0 to 192 hours evaluated in two periods
The area under the plot of plasma concentration of drug against time (non-compartimental method), after drug administration, defined as the area under the curve (AUC). The AUC 0-t is calculated from time 0 (prior to administration of medication) to time t (the time of the last quantifiable concentration), by linear trapezoidal rule. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption.
Time of maximum observed concentration (Tmax)
Time Frame: Collection points from time 0 to 192 hours evaluated in two periods
Time when Cmax is obtained
Maximum observed concentration of drug through time (Cmax)
Time Frame: Collection points from time 0 to 192 hours evaluated in two periods
Cmax is defined as the maximum or "peak" concentration of a drug observed after its administration. Cmax is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed. Measurement obtained directly of the plasma concentration curve of the drug (non-compartimental method). Occurring at Tmax.
Terminal half-life - T1/2
Time Frame: Collection points from time 0 to 192 hours evaluated in two periods
Calculated by formula: T1/2_Kel= Ln(2)/Kel.
First order rate constant associated with the terminal portion of the curve (Kel)
Time Frame: Collection points from time 0 to 192 hours evaluated in two periods
This parameter is estimated by the angular coefficient of the regression line, calculated by the minimum squares method, of the natural logarithm of the concentration versus time for the last four concentrations values (or at least three) above the quantification limit
Secondary Outcomes
No secondary outcomes reported