Topiramate Bioequivalence Study Brazil - Fast - Clinical Trial for Epilepsy, Tonic-Clonic | NCT01439438

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Brazil

Study Type

Interventional

Intervention

Topiramate coated tablet

Topamax® coated tablet

About this trial

This is an interventional other trial for Epilepsy, Tonic-Clonic

Eligibility Criteria

18 Years - 50 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Test formulation

Reference formulation

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

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.

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.

Time of maximum observed concentration (Tmax)

Time when Cmax is obtained

Terminal half-life - T1/2

Calculated by formula: T1/2_Kel= Ln(2)/Kel.

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

Secondary Outcome Measures

Full Information

NCT ID

NCT01439438

First Posted

September 21, 2011

Last Updated

June 27, 2017

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT01439438

Brief Title

Topiramate Bioequivalence Study Brazil - Fast

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.

Study Type

Interventional

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Completed

Study Start Date

July 22, 2011 (Actual)

Primary Completion Date

September 11, 2011 (Actual)

Study Completion Date

September 11, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epilepsy, Tonic-Clonic

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Test formulation

Arm Type

Active Comparator

Arm Description

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

Arm Title

Reference formulation

Arm Type

Active Comparator

Arm Description

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 Type

Drug

Intervention Name(s)

Topiramate coated tablet

Intervention Description

Test formulation

Intervention Type

Drug

Intervention Name(s)

Topamax® coated tablet

Intervention Description

Reference formulation

Primary Outcome Measure Information:

Title

Area under curve of plasma concentration of drug from time 0 (zero) from time t (last measurable concentration)

Description

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 Frame