Clinical trial NCT01439438: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Epilepsy, Tonic-Clonic
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-09-23
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Area under curve of plasma concentration of drug from time 0 (zero) from time t (last measurable concentration)
timeFrame: Collection points from time 0 to 192 hours evaluated in two periods
measure: Maximum observed concentration of drug through time (Cmax)
timeFrame: Collection points from time 0 to 192 hours evaluated in two periods
measure: Area under curve of plasma concentration of drug from the time 0 (zero) extrapolated to infinity (AUC0-inf)
timeFrame: Collection points from time 0 to 192 hours evaluated in two periods
measure: Time of maximum observed concentration (Tmax)
timeFrame: Collection points from time 0 to 192 hours evaluated in two periods
measure: Terminal half-life - T1/2
timeFrame: Collection points from time 0 to 192 hours evaluated in two periods
measure: First order rate constant associated with the terminal portion of the curve (Kel)
timeFrame: Collection points from time 0 to 192 hours evaluated in two periods
Secondary outcomes:
Other outcomes:
Locations:
city: Campinas
country: Brazil
facility: GSK Investigational Site
state: São Paulo
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: