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Trial registered on ANZCTR


Registration number
ACTRN12619001348145
Ethics application status
Approved
Date submitted
14/08/2019
Date registered
1/10/2019
Date last updated
1/10/2019
Date data sharing statement initially provided
1/10/2019
Date results information initially provided
1/10/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
The safety and disposition of metformin in people with liver disease and diabetes already treated with metformin
Scientific title
The pharmacokinetics and safety of metformin in patients with liver disease and diabetes already treated with metformin
Secondary ID [1] 292881 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic liver disease 314008 0
Diabetes 314505 0
Condition category
Condition code
Metabolic and Endocrine 312397 312397 0 0
Diabetes
Oral and Gastrointestinal 312718 312718 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Metformin hydrochloride (oral tablet immediate release formulation).

This is an observational, cross sectional study conducted in patients with liver disease who are already being treated with metformin for their T2DM. The doses of metformin will not be altered for these patients. The duration of observation in each patient is a one-off 2 hour consultation.
Intervention code [1] 315432 0
Not applicable
Comparator / control treatment
Results from the present study will be compared to data previously published examining the pharmacokinetics of metformin in healthy subjects and patients with type 2 diabetes mellitus.

Healthy subject data was obtained from Timmins et al Clin Pharmacokinet. 2005 where subjects were dosed with metformin extended release (500, 1000 and 1500 mg once daily) for 3 weeks followed by metformin extended release 2000 mg once daily or metformin immediate release 1000 mg twice daily for 2 weeks.

Type 2 diabetes mellitus data was obtained from Duong et al Clin Pharmacokinet. 2013 from patients receiving metformin (250-3000 mg/day) either the immediate or extended release formulation.
Control group
Historical

Outcomes
Primary outcome [1] 321036 0
The primary outcome of this study is the monitoring of a composite safety outcome including the concentrations of metformin and blood biochemistry to ensure they are below the safety thresholds of 5 mg/L and 5 mmol/L, respectively.
Timepoint [1] 321036 0
Venous blood samples will be obtained on the day of consultation at anytime post drug administration on up to 6 occasions. These blood samples will be used to determine: metformin concentrations, lactate concentrations, creatinine concentrations, fasting glucose and insulin concentration, and blood biochemistry.
Secondary outcome [1] 373761 0
The secondary outcome is to determine the pharmacokinetics of metformin by monitoring plasma metformin concentrations and using these to estimate an individual's pharmacokinetic parameters (CLMet/F apparent clearance of metformin; Vc/F, apparent volume of distribution of metformin in the central compartment; CLMet/F:CLCr ratio of the apparent clearance of metformin to creatinine clearance) using a population pharmacokinetic analysis approach.
Timepoint [1] 373761 0
The pharmacokinetics of metformin at steady-state (5 half-lives) will be determined from a single plasma metformin concentration obtained on the day of consultation at any time post drug administration. The pharmacokinetics of metformin in study participants will be compared to steady-state pharmacokinetic of metformin in healthy subjects and patients with type 2 diabetes and no known history of chronic liver disease reported in the literature.

Eligibility
Key inclusion criteria
Patients with chronic liver disease who are being treated with metformin for their type 2 diabetes mellitus.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
No exclusion criteria.


Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 14521 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 27535 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 297506 0
Government body
Name [1] 297506 0
National Health and Medical Research Council
Address [1] 297506 0
16 Marcus Clarke Street
Canberra, ACT, 2601
Country [1] 297506 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital, Sydney
Address
390 Victoria Street
Darlinghurst, NSW, 2010
Country
Australia
Secondary sponsor category [1] 296512 0
None
Name [1] 296512 0
Address [1] 296512 0
Country [1] 296512 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298606 0
St Vincent's Hospital HUman Research Ethics Committee
Ethics committee address [1] 298606 0
Research Office
Translational Research Centre
St Vincent's Hospital Sydney
97-105 Boundary Street
Darlinghurst, NSW, 2010
Ethics committee country [1] 298606 0
Australia
Date submitted for ethics approval [1] 298606 0
30/01/2014
Approval date [1] 298606 0
13/05/2014
Ethics approval number [1] 298606 0

Summary
Brief summary
Metformin is the first drug chosen to treat type 2 diabetes mellitus. However, the regulatory label warns against it use in people who also have chronic liver disease (CLD) but there is little published data to support this warning. Despite this, metformin is used in patients with CLD. This study will investigate the safety and pharmacokinetics of metformin in patients with CLD who are already prescribed metformin to treat their type II diabetes mellitus (T2DM) . We hypothesis that metformin, at doses adjusted based on renal function, can be safely administered to patients with CLD. Further, the pharmacokinetics of metformin in patients with CLD will be similar to those reported in patient with T2DM and no CLD.
Trial website
NA
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77638 0
Prof Richard Day
Address 77638 0
Therapeutics Centre, Level 2 Xavier Building
St Vincent's Hospital, Sydney
390 Victoria Street, Darlinghurst, 2010, NSW
Country 77638 0
Australia
Phone 77638 0
+61 2 8382 2331
Fax 77638 0
+61 2 8382 2724
Email 77638 0
r.day@unsw.edu.au
Contact person for public queries
Name 77639 0
Dr Sophie Stocker
Address 77639 0
Therapeutics Centre, Level 2 Xavier Building
St Vincent's Hospital, Sydney
390 Victoria Street, Darlinghurst, 2010, NSW
Country 77639 0
Australia
Phone 77639 0
+61 2 8382 2617
Fax 77639 0
+61 2 8382 2724
Email 77639 0
sophie.stocker@svha.org.au
Contact person for scientific queries
Name 77640 0
Prof Richard Day
Address 77640 0
Therapeutics Centre, Level 2 Xavier Building
St Vincent's Hospital, Sydney
390 Victoria Street, Darlinghurst, 2010, NSW
Country 77640 0
Australia
Phone 77640 0
+61 2 8382 2331
Fax 77640 0
+61 2 8382 2724
Email 77640 0
r.day@unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary