Bioavailability Of Flucloxacillin Capsules (250 mg and 500 mg)

A Mono-center, Open, Randomized, Three-way, Twelve-sequence, Cross-over Study to Determine the Extent of Absorption (Absolute Bioavailability), Rate of Absorption and to Further Characterize Distribution and Elimination Characteristics of a Commercial 250 mg and a 500 mg Capsule of Flucloxacillin Each Given as a Single Oral Dose vs. One 250 or 500 mg Intravenous Dose to 24 Healthy Male and/or Female Subjects in the Fasting State

Primary objective:To study the absolute bioavailability, distribution and elimination parameters of flucloxacillin from two oral formulations of flucloxacillin in healthy male and/or female subjects.

Study Overview

• Status: Completed
• Conditions: Infections, Bacterial
• Intervention / Treatment: Drug: flucloxacillin 250 mg; Drug: flucloxacillin 500 mg

Detailed Description

A mono-center, open, randomized, three-way, twelve-sequence, cross-over study to determine the extent of absorption (absolute bioavailability), rate of absorption and to further characterize distribution and elimination characteristics of a commercial 250 mg and a 500 mg capsule of flucloxacillin each given as a single oral dose vs. one 250 or 500 mg intravenous dose to 24 healthy male and/or female subjects in the fasting state

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mecklenburg-Vorpommern
    • Greifswald, Mecklenburg-Vorpommern, Germany, 17487
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers,
• Caucasians,
• Body Mass Index (BMI) between 19 and 27 kg/m 2;
• physically and mentally healthy as judged by means of a medical and standard lab examination;
• non-smokers,
• ex-smokers or moderate smoker.

Exclusion criteria:

• medical history,
• vital signs,
• physical examination,laboratory tests (blood and/or urine) with evidence of clinically significant conditions;
• 12-lead electrocardiogram (ECG) with clinically significant abnormality;acute infection within 2 weeks preceding 1st study drug administration;any medication on a regular basis (exception females: oral contraceptives) and/or tricyclic antidepressants, antacids, histamine H2-receptor antagonists, antibiotics,
• non steroid anti-inflammatory drugs or anticoagulants within 8 weeks before the 1st study drug administration and/or no agreement to take any of those drugs including Over-the-counter (OTC) drugs until the end of the follow- up examination;
• no agreement not to take any medication,including OTC medicine, antacids, or analgesics within 2 weeks before 1st drug administration until the end of the follow-up examination;special diet or loss of > 5 kg within last month from a weight reduction diet; regularly consume of large quantities of alcohol (> 20g/day) and/or beverages containing methylxanthines e.g. caffeine (> 0.5L/day altogether);
• no agreement not to consume: - any beverages or foods containing alcohol 48 h prior to 1st study drug administration until end of the follow-up examination;
• any grapefruit products 7 days prior 1st study drug administration until end of the follow-up examination,
• any beverages or foods containing methylxanthines as well as fruit-juices and any foods containing poppy seed 48 h before 1st drug administration of either study period until last blood sample of the respective study period was collected,
• not to consume chewing during confinement;
• history of: - allergy to flucloxacillin,
• B-lactams and/or related drugs,
• known hypersensitivity against the inactive ingredients of the study medication,
• hypersensitivity to multiple drugs,
• allergic diseases,
• acute hay fever,
• previous history of flucloxacillin-associated jaundice/hepatic dysfunction,
• alcohol or drug abuse,
• epilepsy or other seizure,
• psychiatric illness, e.g. latent or manifest depression schizophrenia, or neurosis,
• respiratory diseases,
• surgery of the gastrointestinal tract (except appendectomy),
• kidney diseases,
• bleeding/coagulation disorder or severe anaemia,
• glucose-6-phosphate dehydrogenase deficiency and/or chronic treatment or chronic pathology;
• metabolic disease;
• evidence for disorder in the metabolism of pharmaceuticals or other foreign compounds; cardiovascular diseases e.g. hypertension, hypotension or bradycardia;
• associated disease that would interfere with the clinical course of the trial;
• major illness during 3 month before commencement of the screening period,
• gastrointestinal diseases;
• reported or positive results from test of drugs of abuse (amphetamines, opiates, barbiturate, methadone, cannabinoids, cocaine, benzodiazepines);
• Positive test for: alcohol, Hepatitis-B-antigen or Hepatitis-C-antibody, HIV-antibody;blood donor or blood loss including plasmapheresis within the last 3 months before the 1st study drug administration;
• intake of depot injectable solutions (including study medication) within 6 month before 1st study administration;
• intake of enzyme-inducing and/or organotoxic drugs within 4 weeks before 1st study drug administration;for females only: positive results from pregnancy tests;does not use or not agree to use adequate contraceptive methods during the study;
• lactating woman.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects receiving flucloxacillin 250 mg; Subjects will be randomized to receive single oral dose of 250 mg flucloxacillin capsule and 250 mg Intravenous dose	Drug: flucloxacillin 250 mg; Subjects will be randomized to receive single oral dose of 250 mg flucloxacillin capsule and 250 mg Intravenous dose; Other Names: flucloxacillin
Experimental: Subjects receiving flucloxacillin 500 mg; Subjects will be randomized to receive single oral dose of 500 mg flucloxacillin capsule and 500 mg Intravenous dose	Drug: flucloxacillin 500 mg; Subjects will be randomized to receive single oral dose of 500 mg flucloxacillin capsule and 500 mg Intravenous dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute (Abs.) bioavailability, max. plasma conc., concentration-time curve (AUC) from 0 hto the last quantifiable conc., AUC from 0 h to infinity), timepoint of max. plasma conc., Halflife of drug elimination during the terminal phase	Up to 60 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Elimination rate constant, total Clearance, Volume of distribution at steady state, Volume of distribution during the terminal phase, residual area	Up to 60 Days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2005
• Primary Completion (Actual): February 8, 2005
• Study Completion (Actual): February 8, 2005

Study Registration Dates

• First Submitted: July 27, 2006
• First Submitted That Met QC Criteria: July 27, 2006
• First Posted (Estimate): July 31, 2006

Study Record Updates

• Last Update Posted (Actual): September 29, 2017
• Last Update Submitted That Met QC Criteria: September 27, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: bioavailability flucloxacillin
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Floxacillin
• Other Study ID Numbers: 103811

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No