Prostatic Hyperplasia
Conditions
Keywords
Bioequivalence, Healthy volunteers, tamsulosin hydrochloride, Fed administration
Brief summary
It will be an open-label, randomized, laboratory-blind, crossover study with 02 treatments, 02 sequences, and 02 periods, in which the volunteers receive, in each period, the test formulation or the reference formulation, under fed conditions.
Detailed description
It will be an open-label, randomized, laboratory-blind, crossover study with 02 treatments, 02 sequences, and 02 periods, in which the volunteers receive, in each period, the test formulation or the reference formulation, under fed conditions. The treatment's sequence attributed to each volunteer on the study period is determined by a randomization list, which is generated by PROC PLAN from SAS version 9.1.3 system. The formulations will be administered as a single oral dose followed by blood collections between, at least, 3 to 5 half-lives. The treatment's periods may obey a minimum interval of 7 half lives between them (period for drug's whole elimination by the organism).
Interventions
DRUGTest formulation
tamsulosin hydrochloride 0,4 mg (Synthon BV)
SECOTEX® (tamsulosin hydrochloride) 0,4 mg (Boehringer Ingelheim)
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Exclusion criteria
* The volunteer has a known hypersensitivity to the study drug (tamsulosin hydrochloride) 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 investigator criteria; * The results of the laboratory exams are out of the values considered as normal according this protocol's rules, unless that they are considered as clinically irrelevant by the investigator; * Volunteer is a smoker; * The volunteer ingests more than 5 cups of coffee or tea a day; * Has history of alcohol or drugs abuse; * History of serious adverse reactions or hypersensitivity to any drug; * Use of any regular drug within the 02 weeks that preceded study's initiation or treatment within the 03 previous months, that preceded study's initiation, with any drug that presents toxic, or volunteer consumed inductive drugs and/or enzymatic inhibitor (CYP450 - hepatic), within the 04 weeks that preceded the study's initiation; * Volunteer was hospitalized for any reason within the 08 weeks of the beginning of the study's first period of treatment and the post study assessment date; * Participation in any experimental study or ingestion of any experimental drug within the 06 previous months; * Volunteer consumed alcohol in 48 hours prior to the admission to the study or consumed foods or beverages that contain grapefruit until 07 days previous to each study period. INCLUSION CRITERIA: * Male; * Age between 18 and 50 years; * Body mass index ≥ 19 and ≤28,5; * Good health conditions or without significant illness, by judgment of a legally qualified professional, according the rules defined in Protocol, and according the following evaluations: clinical history, pressure and pulse measures, physical and psychological exam, ECG, and additional laboratory exams; * Capable to understand the study's nature and aim, including the risks and adverse effects and with intention to cooperate with the researcher and to act in compliance with the requirements of the whole assay; this will be confirmed by the Informed Consent's signature.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC 0-t | Day 1 (day that blood collections started) to Day 4 (Period 1) and Days 8 to 11 (Period 2) | The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC from time 0 (prior to administration of medication) to time t (the time of the last quantifiable concentration) was calculated using the trapezoidal method. This method consists of the sum of the trapezoids' areas, determined by the collection times and their concentrations. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. ng, nanograms; ml, milliliter. |
| AUC0-infinity | Day 1 (day that blood collections started) to Day 4 (Period 1) and Days 8 to 11 (Period 2) | The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug) was calculated using the trapezoidal method. This method consists of the sum of the trapezoids' areas, determined by the collection times and their concentrations. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. |
| Cmax | Day 1 (day that blood collections started) to Day 4 (Period 1) and Days 8 to 11 (Period 2) | 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. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants Receiving Both Test Product and Reference Product Participants receiving either test product: tamsulosin hydrochloride 0.4 mg prolonged release hard gelatin capsule in Period 1; followed by reference product: SECOTEX (tamsulosin hydrochloride) 0.4 mg prolonged release hard gelatin capsule in Period 2 or reference product in Period 1 and test product in Period 2 | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 1 | 0 |
| Period 1 | Protocol Violation | 0 | 1 |
| Period 1 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Participants Receiving Both Test Product and Reference Product |
|---|---|
| Age, Continuous | 30.20 Years STANDARD_DEVIATION 7.36 |
| Race/Ethnicity, Customized Black | 2 participants |
| Race/Ethnicity, Customized Caucasian | 35 participants |
| Race/Ethnicity, Customized Mulatto | 3 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 20 | 8 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
AUC0-infinity
The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug) was calculated using the trapezoidal method. This method consists of the sum of the trapezoids' areas, determined by the collection times and their concentrations. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption.
Time frame: Day 1 (day that blood collections started) to Day 4 (Period 1) and Days 8 to 11 (Period 2)
Population: Participants who completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | AUC0-infinity | 237.87 ng.h/ml | Standard Deviation 125.56 |
| Reference Product | AUC0-infinity | 228.36 ng.h/ml | Standard Deviation 103.28 |
90% CI: [95, 109.33]
Primary
AUC 0-t
The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC from time 0 (prior to administration of medication) to time t (the time of the last quantifiable concentration) was calculated using the trapezoidal method. This method consists of the sum of the trapezoids' areas, determined by the collection times and their concentrations. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. ng, nanograms; ml, milliliter.
Time frame: Day 1 (day that blood collections started) to Day 4 (Period 1) and Days 8 to 11 (Period 2)
Population: Participants who completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | AUC 0-t | 229.87 ng per hour per ml (ng.h/ml) | Standard Deviation 119.88 |
| Reference Product | AUC 0-t | 220.85 ng per hour per ml (ng.h/ml) | Standard Deviation 98.6 |
90% CI: [94.91, 109.39]
Primary
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.
Time frame: Day 1 (day that blood collections started) to Day 4 (Period 1) and Days 8 to 11 (Period 2)
Population: Participants who completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Cmax | 14.06 ng/ml | Standard Deviation 6.22 |
| Reference Product | Cmax | 14.88 ng/ml | Standard Deviation 5.93 |
90% CI: [86.33, 102.44]