Topiramate Bioequivalence Study Brazil - Fast

Epilepsy, Tonic-Clonic Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01439438
• Other study ID #: 116144
• Status: Completed
• Phase: Phase 1
• First received: September 21, 2011
• Last updated: June 27, 2017
• Start date: July 22, 2011
• Est. completion date: September 11, 2011

Study information

• Verified date: June 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: September 11, 2011
• Est. primary completion date: September 11, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Male

• 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

• Treatment within the 03 previous months of the study with any known drug that presents toxic potential for important organs

• The volunteer participated in any experimental study or ingested any experimental drug within the 06 months that precede the beginning of this study and the assessment date

• The volunteer donated or lost 450 mL or more of blood within the 03 months that preceded to the study initiation or donated more than 1500 mL within 12 months between the beginning of the study and the assessment date

• Consume of inductive drugs and/or enzymatic inhibitors (CYP450 - hepatic), that are toxic for the organism or presenting long half-life's elimination within the 04 weeks that precede the study's initiation

• Consume of alcohol in 48 hours antecedents to the admission to the study and along the study period

• Consume of food or beverages containing grapefruit (grapefruit) within 24 hours preceding each study period

• History of serious adverse reactions or hypersensitivity to any drug

• The volunteer has any condition that obstructs his participation in the study according the investigator's judgement

Related Conditions & MeSH terms

• Epilepsy, Generalized
• Epilepsy, Tonic-Clonic

Intervention

Drug:
• Topiramate coated tablet
Test formulation
• Topamax® coated tablet
Reference formulation

Locations

Country	Name	City	State
Brazil	GSK Investigational Site	Campinas	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under curve of plasma concentration of drug from time 0 (zero) from time t (last measurable concentration)	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.	Collection points from time 0 to 192 hours evaluated in two periods
Primary	Maximum observed concentration of drug through time (Cmax)	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.	Collection points from time 0 to 192 hours evaluated in two periods
Primary	Area under curve of plasma concentration of drug from the time 0 (zero) extrapolated to infinity (AUC0-inf)	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.	Collection points from time 0 to 192 hours evaluated in two periods
Primary	Time of maximum observed concentration (Tmax)	Time when Cmax is obtained	Collection points from time 0 to 192 hours evaluated in two periods
Primary	Terminal half-life - T1/2	Calculated by formula: T1/2_Kel= Ln(2)/Kel.	Collection points from time 0 to 192 hours evaluated in two periods
Primary	First order rate constant associated with the terminal portion of the curve (Kel)	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	Collection points from time 0 to 192 hours evaluated in two periods

External Links

•   Results for study 116144 can be found on the GSK Clinical Study Register.