Amoxicillin Bioequivalence Study Brazil - Fast

Evaluation of Pharmaceutical Bioequivalence of Amoxicillin Trihydrate - Clamoxyl 500mg/5mL (Glaxo Wellcome Production.) in the Form Powder for Oral Suspension Versus Amoxil ® 500mg/5mL (GlaxoSmithKline Mexico SA) in the Form of Powder for Oral Suspension in Healthy Volunteers and Fasting, Using Techniques of Liquid Chromatography

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.

Study Overview

• Status: Completed
• Conditions: Infections, Bacterial
• Intervention / Treatment: Drug: Amoxicillin powder for oral suspension (Clamoxyl®) 500mg/5mL; Drug: Amoxil® 500mg/5mL powder for oral suspension

Detailed Description

This study is prospective, open-label, randomized, crossover, single dose, with 02 treatments, 02 sequences and 02 periods. The objective is to confirm if two formulations of Amoxicillin trihydrate, in the form powder for oral suspension, are bioequivalent. The test product is Amoxicillin trihydrate - Clamoxyl 500mg/5mL (Glaxo Wellcome Production.) in the form powder for oral suspension and reference product is Amoxil ® 500mg/5mL (GlaxoSmithKline Mexico SA) in the form of powder for oral suspension. Twenty eight healthy volunteers, of both genders, were evaluated. The volunteers received, in each period, the reference or the test formulation, according to the randomization list, under fasting conditions. In each period blood samples are collected in the following times: 0.00 (prior to administration of medication); 0.25; 0.50; 0.75; 1.00; 1.25; 1.50; 1.75; 2.00; 2.50; 3.00; 4.00; 5.00; 6.00; 8.00 (after administration of medication). 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 Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Goiás
    • Goiania, Goiás, Brazil
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 18 and 50 years
• Body mass index between 18,5 and 25,0, can vary up to 15% for the upper limit (18,5 and 28,75)
• Good health conditions
• Obtain signed informed consent

Exclusion Criteria:

• Results of laboratory tests outside the normal limits, unless they are considered clinically irrelevant
• The volunteers who underwent surgery or who were hospitalized for any reason before the start of the study will be reviewed by the physician on admission in the study, observing a period of exclusion of 4 to 8 weeks
• Positive test for hepatitis B, hepatitis C or HIV in pre study evaluation
• Known hypersensitivity to the study drug or to compounds chemically related
• Use of experimental drug or participation in any clinical study within 6 months prior to study initiation
• Use of regular medication within 2 weeks prior to study initiation
• History of alcohol or drugs abuse or intake of alcohol within 24 hours prior to the period of confinement
• Consume of inductive drugs and/or enzymatic inhibitors (CYP450 - hepatic), that are toxic for the organism or presenting long half-life's elimination within 30 days prior to study initiation
• Use of MAO and serotonin reuptake inhibitors within 2 weeks prior to study initiation
• Volunteers with psychiatric or psychological illness unless they are considered clinically irrelevant by the investigator
• History or presence of hepatic, renal or gastrointestinal illness or other condition that interferes on drug's absorption, distribution, excretion or metabolism
• History of neurological, endocrine, pulmonary, hematologic, immune, brain, metabolic or cardiovascular illness
• Hypo or hypertension of any etiologic that needs pharmacologic treatment
• History or clinical case of myocardial infarction, angina and/or heart failure
• The volunteer donated or lost 450 mL or more of blood within the 3 months prior to the study initiation
• The volunteer has any condition that obstructs his/her participation in the study according the investigator's judgement
• Smoking
• Positive beta HCG exam for women
• Breastfeeding women
• Women making use of contraceptive medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Test formulation; Test product: Amoxicillin powder for oral suspension (Clamoxyl®) 500mg/5mL in Period 1; followed by 14-days washout period during which no medication was administered; followed by reference product: Amoxil® 500mg/5mL in Period 2.	Drug: Amoxicillin powder for oral suspension (Clamoxyl®) 500mg/5mL; Test formulation
Active Comparator: Reference formulation; Reference product: Amoxil® 500mg/5mL powder for oral suspension in Period 1; followed by 14-days washout period during which no medication was administered; followed by test product: Amoxicillin powder for oral suspension (Clamoxyl®) 500mg/5mL in Period 2	Drug: Amoxil® 500mg/5mL powder for oral suspension; Reference formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve of Plasma Concentration of Drug From Time 0 (Zero) to t (Last Measurable Concentration) (AUC0-t)	The area under the plot of plasma concentration of drug against time (non-compartmental method), after drug administration, is defined as the area under the curve (AUC). AUC0-t is calculated from time 0 (prior to administration of medication) to time t (the time of the last quantifiable concentration). AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. ng, nanograms; mL, milliliter.	Collection points (hours [hrs]): 0.00; 0.25; 0.50; 0.75; 1.00; 1.25; 1.50; 1.75; 2.00; 2.50; 3.00; 4.00; 5.00; 6.00; 8.00 evaluated in both periods (Day 1 of Period 1 [Day 1 of study]; Day 1 of Period 2 [Day 15 of study])
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 is obtained directly from the plasma concentration curve of the drug (non-compartmental method).	Collection points (hrs): 0.00; 0.25; 0.50; 0.75; 1.00; 1.25; 1.50; 1.75; 2.00; 2.50; 3.00; 4.00; 5.00; 6.00; 8.00 evaluated in both periods (Day 1 of Period 1 [Day 1 of study]; Day 1 of Period 2 [Day 15 of study])
Area Under the Curve of Plasma Concentration of Drug From Time 0 (Zero) Extrapolated to Infinity (AUC0-inf)	Measurement of AUC0-inf is obtained directly from the plasma concentration curve of drug against time (non-compartmental method). AUC0-inf is calculated from time 0 (prior to administration of medication) extrapolated to infinity, by using the formula AUC0-inf = AUC0-t + 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. AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption.	Collection points (hrs):0.00; 0.25; 0.50; 0.75; 1.00; 1.25; 1.50; 1.75; 2.00; 2.50; 3.00; 4.00; 5.00; 6.00; 8.00 evaluated in both periods (Day 1 of Period 1[Day 1 of study]; Day 1 of Period 2 [Day 15 of study])
Time of Maximum Observed Concentration (Tmax)	The time of maximum observed concentration (Tmax) is obtained directly from the plasma concentration curve of the drug by non-compartimental method. Tmax is of particular use in measuring bioavailability, by measuring the time at which the maximum concentration is achieved.	Collection points (hrs):0.00; 0.25; 0.50; 0.75; 1.00; 1.25; 1.50; 1.75; 2.00; 2.50; 3.00; 4.00; 5.00; 6.00; 8.00 evaluated in both periods: (Day 1 of Period 1 [Day 1 of study]; Day 1 of Period 2 [Day 15 of study])
Percentage of AUC0-inf That is Due to Extrapolation From the Time of the Last Measurable Concentration to Infinity (AUC%Extrapolation)	The percentage of AUC0-inf that is due to extrapolation from Tlast to infinity (AUC%Extrapolation) is calculated by using the formula AUC_%extrapolation = 100*(AUC0-inf minus AUC0-t)/AUC0-inf. The function of this parameter is to provide information about what percentage of the theoretical curve (AUC0-inf) was possible to determine experimentally (AUC0-t) Therefore, on average, it is expected that the residual area (AUCextrapolation) is not greater than 20%.	Collection points (hrs):0.00; 0.25; 0.50; 0.75; 1.00; 1.25; 1.50; 1.75; 2.00; 2.50; 3.00; 4.00; 5.00; 6.00; 8.00 evaluated in both periods: (Day 1 of Period 1 [Day 1 of study]; Day 1 of Period 2 [Day 15 of study])
Terminal Half-life (T1/2_Kel)	T1/2_Kel is calculated by using the formula T1/2_Kel = Ln(2)/Kel.T1/2 is of particular use in measuring bioavailability, by measuring the elimination of the product.	Collection points (hrs):0.00; 0.25; 0.50; 0.75; 1.00; 1.25; 1.50; 1.75; 2.00; 2.50; 3.00; 4.00; 5.00; 6.00; 8.00 evaluated in both periods: (Day 1 of Period 1 [Day 1 of study]; Day 1 of Period 2 [Day 15 of study])
First-order Rate Constant Associated With the Terminal Portion of the Curve (Kel)	This parameter is estimated via linear regression of time versus log concentration. It allows for the obtainment of estimates of T1/2 (T1/2=ln(2)/Kel) considering the schedule and the detection limits defined.	Collection points (hrs):0.00; 0.25; 0.50; 0.75; 1.00; 1.25; 1.50; 1.75; 2.00; 2.50; 3.00; 4.00; 5.00; 6.00; 8.00 evaluated in both periods: (Day 1 of Period 1 [Day 1 of study]; Day 1 of Period 2 [Day 15 of study])

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2011
• Primary Completion (Actual): June 11, 2011
• Study Completion (Actual): June 11, 2011

Study Registration Dates

• First Submitted: September 8, 2011
• First Submitted That Met QC Criteria: September 8, 2011
• First Posted (Estimate): September 12, 2011

Study Record Updates

• Last Update Posted (Actual): June 20, 2018
• Last Update Submitted That Met QC Criteria: June 18, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Amoxicillin
• Other Study ID Numbers: 115954