Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12613001205729
Ethics application status
Not yet submitted
Date submitted
29/10/2013
Date registered
4/11/2013
Date last updated
4/11/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of probenecid on boosting cephalexin pharmacokinetics in healthy volunteers
Scientific title
Effect of probenecid on cephalexin pharmacokinetics in healthy volunteers
Secondary ID [1] 283472 0
nil
Universal Trial Number (UTN)
U1111-1149-5732
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Antibiotic pharmacokinetics 290387 0
Condition category
Condition code
Infection 290780 290780 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single simultaneous dose of probenecid 500 mg orally and cephalexin 1 g orally. Treatment will be directly observed by the lead investigator
Intervention code [1] 288182 0
Treatment: Drugs
Comparator / control treatment
A single dose of cephalexin 1 g orally. Treatment will be directly observed by the lead investigator. The intervention and control treatments will be 7 days apart.
Control group
Active

Outcomes
Primary outcome [1] 290776 0
Serum concentration of free and protein-bound cephalexin, measured by liquid chromatography-mass spectrometry
Timepoint [1] 290776 0
Tests at baseline, 30 min, 1 hour, 90 min, 2 hours, 150 min, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours
Secondary outcome [1] 305263 0
Side effects (e.g., nausea, rash, headache), measured by questionnaire and direct observation by lead investigator
Timepoint [1] 305263 0
Monitored continually for 12 hours

Eligibility
Key inclusion criteria
Adult
Healthy
Taking no other medication
Normal renal function
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Allergy to cephalosporins, penicillins
Pregnant

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Subjects are volunteers
Each subject will be screened to make sure he or she meets the study criteria
The intervention treatment (probenecid and cephalexin) will be given on one study day and the control treatment (cephalexin alone) will be given on another study day
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
There is no randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s

Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Repeated measures1 way ANOVA
post-hoc Tukey’s test
(bio)equivalence testing if no differences

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
19/01/2014
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment outside Australia
Country [1] 5541 0
New Zealand
State/province [1] 5541 0

Funding & Sponsors
Funding source category [1] 288179 0
Charities/Societies/Foundations
Name [1] 288179 0
Nelson Hospital Research and Education Trust Fund
Country [1] 288179 0
New Zealand
Primary sponsor type
Individual
Name
Richard Everts
Address
Infectious Diseases Physician and Medical Microbiologist
Nelson Bays Primary Health
PO Box 1776
Nelson 7040
Country
New Zealand
Secondary sponsor category [1] 286902 0
None
Name [1] 286902 0
Address [1] 286902 0
Country [1] 286902 0
Other collaborator category [1] 277670 0
Individual
Name [1] 277670 0
Professor Steve Chambers
Infectious Diseases Specialist
Address [1] 277670 0
Department of Infectious Diseases
Christchurch Hospital
Private Bag 4710
Christchurch 8140
Country [1] 277670 0
New Zealand
Other collaborator category [2] 277671 0
Individual
Name [2] 277671 0
Professor Evan Begg
Clinical Pharmacologist
Address [2] 277671 0
Clinical Pharmacology Department
Canterbury DHB
PO Box 4345
Christchurch 8140
Country [2] 277671 0
New Zealand
Other collaborator category [3] 277672 0
Individual
Name [3] 277672 0
Professor John Turnidge
Microbiologist and Infectious Diseases Specialist
Address [3] 277672 0
SA Pathology
Women's and Children's Hospital
72 King William Rd
North Adelaide, SA, 5006
Country [3] 277672 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 290095 0
NZ Health and Disability Ethics Committee
Ethics committee address [1] 290095 0
Ministry of Health
PO Box 5013
Wellington 6145
Ethics committee country [1] 290095 0
New Zealand
Date submitted for ethics approval [1] 290095 0
01/11/2013
Approval date [1] 290095 0
Ethics approval number [1] 290095 0

Summary
Brief summary
The effect of probenecid on cephalexin has already been studied in the late 1960s and early 1970s, but with less accurate methods and fewer volunteers. We wish to repeat the study using highly accurate methods and 10 volunteers. The boosting effect of probenecid on cephalexin may have very widespread positive medical, social and economic consequences. For example, it may allow cephalexin (with probenecid) to be given only twice daily rather than three or four times daily (on its own) for people in the community with mild infections, improving convenience and compliance. In addition, probenecid-boosted oral cephalexin may be as powerful as intravenous antibiotics, meaning that fewer patients with moderate infections will need admission to hospital, selected patients will be able to be discharged from hospital earlier, and commonly prescribed outpatient intravenous antibiotic programmes will no longer be needed in many situations. This could save NZ up to $4 million in health-care costs per year and improve patient outcomes.

I was approved an almost identical study by the NZ Ethics Committee last year (NZ HDEC # NZ/1/4C71012), which I did not register as a clinical trial with ANZCTR but was completed with very clear and positive results. I am in the process of applying for approval of the probenecid and cephalexin study with the NZ Ethics Committee.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 43922 0
Dr Richard Everts
Address 43922 0
Infectious Diseases Specialist and Medical Microbiologist
Nelson Bays Primary Health
PO Box 1776
Nelson 7040
Country 43922 0
New Zealand
Phone 43922 0
(+64) 3 5391170
Fax 43922 0
(+64) 4 5394958
Email 43922 0
[email protected]
Contact person for public queries
Name 43923 0
Dr Richard Everts
Address 43923 0
Infectious Diseases Specialist and Medical Microbiologist
Nelson Bays Primary Health
PO Box 1776
Nelson 7040
Country 43923 0
New Zealand
Phone 43923 0
(+64) 3 5391170
Fax 43923 0
(+64) 4 5394958
Email 43923 0
[email protected]
Contact person for scientific queries
Name 43924 0
Dr Richard Everts
Address 43924 0
Infectious Diseases Specialist and Medical Microbiologist
Nelson Bays Primary Health
PO Box 1776
Nelson 7040
Country 43924 0
New Zealand
Phone 43924 0
(+64) 3 5391170
Fax 43924 0
(+64) 4 5394958
Email 43924 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseProbenecid effects on cephalexin pharmacokinetics and pharmacodynamics in healthy volunteers.2021https://dx.doi.org/10.1016/j.jinf.2021.05.037
N.B. These documents automatically identified may not have been verified by the study sponsor.