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Trial registered on ANZCTR


Registration number
ACTRN12616000330448
Ethics application status
Approved
Date submitted
10/04/2013
Date registered
14/03/2016
Date last updated
26/11/2018
Date data sharing statement initially provided
26/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I/2 trial of Deferasirox in patients with type 2 diabetes
Scientific title
Phase I/II safety and glycaemic efficacy trial of Deferasirox in patients with type 2 diabetes
Secondary ID [1] 262994 0
Nil
Universal Trial Number (UTN)
Trial acronym
DiPT2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 270725 0
Condition category
Condition code
Metabolic and Endocrine 270901 270901 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Open label study of deferasirox.
1 intervention arm - everyone will receive DFS.
This will start at 5mg/kg/day and increase monthly in 5mg/kg/day steps until efficacy, side effects or significantly decreased iron levels. Patients will only increase the dose if there is no efficacy, no significant side-effects and iron studies do not indicate lower overall iron status. The dose may be decreased if their are side effects, including down to 2.5mg/kg/day.
Maximum dose 20mg/kg. Maximum duration 6 months.
Each person will (as above) go up in 5mg/kg steps.
DFS is administered as an oral tablet. Adherence strategies include tablet counts of returned medication and lab tests for iron studies.
Intervention code [1] 269342 0
Treatment: Drugs
Comparator / control treatment
Baseline for each patient (paired testing after run-in). There is no control group. This is an open label dose finding and safety study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 279574 0
Safety assessment (number of serious adverse events). Main side effects are nausea and other GI effects. Rash occurs sometimes, a rise in serum creatinine.
The known side-effects will be assessed by history and path testing. Previously unrecognised ones will be assessed by open questions and general pathology tests.
Timepoint [1] 279574 0
Weekly for at least 4 weeks, then fortnightly for 4 weeks then monthly over the course of the study.
Primary outcome [2] 286728 0
Change in BMI assessed by digital scales and stadiometer.
Timepoint [2] 286728 0
At 3-4 months (the closest study visit to 3 months).
Secondary outcome [1] 296545 0
Serum Fructoasamine
Timepoint [1] 296545 0
2-monthly while taking study medication.
Secondary outcome [2] 296546 0
Weight.
Measured with scales
Timepoint [2] 296546 0
Weekly for 4 weeks, fornightly for 2 weeks then monthly over the course of the study
Secondary outcome [3] 320951 0
Adiposity assessed by bioimpedance on scales.
Timepoint [3] 320951 0
Weekly for 4 weeks, fornightly for 2 weeks then monthly over the course of the study
Secondary outcome [4] 321649 0
Waist circumference measured with a tape measure.
Timepoint [4] 321649 0
Weekly for 4 weeks, fornightly for 2 weeks then monthly over the course of the study

Eligibility
Key inclusion criteria
T2D diagnosed within the last 10 years, with an HbA1c of 7.5%-10%, inclusive. The patients may be treated with diet and exercise or with metformin alone, at a stable dose for the preceding 3 months. After 8 weeks, if their glucose control is not improving, they will be allowed to start other hypoglycaemic medications.
Minimum age
30 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Age <30 (less likely to be T2DM), or >75 years
BMI <25kg/m2, or <23kg/m2 if of South East Asian or Subcontinental Asian ethnicity
Body weight >120kg.
Elevated serum creatinine outside the normal range or eGFR <60ml/min
Anaemia, thrombocytopaenia, iron deficiency or known iron overload conditions
Low serum ferritin (<150ng/ml for men or <100ng/ml for women)
Any grade of known diabetic retinopathy above mild non-proliferative changes
Because of the reported low incidence of cataracts, all patients must have a diabetic eye screen within the preceding year and patients with cataracts will be excluded
Microalbuminuria or macroalbuminuria (confirmed on repeat testing), excluded due to the reported rare side effect of Fanconi syndrome
Significant proteinuria (confirmed on repeat testing). Defined as a urinary protein:creatinine ratio of >1mg/mg in a mid-stream sample
Unstable angina, congestive cardiac failure, stable angina with onset <500m of walking or claudication with onset distance <500m, all due to the small risk of inducing anaemia
Pregnancy, breast-feeding or lack of reliable contraception in women of child-bearing age
Known malignancy
Liver function tests >twice the upper limit of the normal reference range
Inability to give informed consent
Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator’s opinion makes it undesirable for the patient to participate in the study, or which would jeopardise compliance with the protocol.
Medical co-morbidities that have the potential to be exacerbated by or contra-indicate treatment with deferasirox

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)
Open label study.
For each cohort, up to 6 patients will be enrolled. Each cohort will consist of newly enrolled patients. Once each patient has received treatment for 28 days the decision of which deferasirox dose for each patient will be evaluated. The dose will be increased by 5mg/kg/day if patients have not achieved efficacy, significant side effects or decrease in iron status towards the lower limits of normal.
The deferasirox doses to be investigated will be 5mg/kg/day and 10mg/kg/day. Potentially, 15mg/kg/day and 20mg/kg/day doses may be explored if the smaller doses do not lower serum ferritin and do not cause DLT and after consultation and approval from Novartis for the dose change. Depending on the side effect profile, 2.5mg/kg/day may be evaluated.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Multiple doses to be tested
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
No formal power calculation performed.
Paired testing versus baseline values and comparison of endpoint results in people on differing study medications at the end of the study.
This is a dose finding study, we are interested in determining what doses are tolerated and either affect weight/ diabetes or cause altered iron status but have no effect on weight / diabetes. In mice 4 mice is enough to achieve statistical significance.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
1/06/2016
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 858 0
Westmead Hospital - Westmead
Recruitment hospital [2] 859 0
Blacktown Hospital - Blacktown

Funding & Sponsors
Funding source category [1] 284890 0
Hospital
Name [1] 284890 0
Westmead Hospital
Country [1] 284890 0
Australia
Primary sponsor type
Hospital
Name
Westmead Hospital
Address
Hospital Rd,
Westmead.
NSW. 2145
Country
Australia
Secondary sponsor category [1] 291640 0
None
Name [1] 291640 0
None
Address [1] 291640 0
None
Country [1] 291640 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286889 0
Westmead HREC
Ethics committee address [1] 286889 0
Westmead Hospital,
Westmead. NSW. 2145
Ethics committee country [1] 286889 0
Australia
Date submitted for ethics approval [1] 286889 0
01/06/2013
Approval date [1] 286889 0
01/02/2014
Ethics approval number [1] 286889 0

Summary
Brief summary
This study is an open-label, non-randomized, dose-defining study of daily deferasirox in overweight or obese patients with type 2 diabetes (T2D). This study is designed to assess the feasibility (safety and tolerability) of deferasirox administered daily, based on the rate of Dose Limiting Toxicities (DLTs), i.e. pre-defined adverse events. A DLT is defined as an adverse event or abnormal laboratory value occurring at any time which is assessed as clinically relevant which is considered to be related to the study treatment, unrelated to disease, disease progression, inter-current illness, or concomitant medications, and warrants stopping or reducing the medication. Toxicities will be assessed using the NCI CTCAE, version 3.0.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes

Contacts
Principal investigator
Name 33123 0
Prof Jenny Gunton
Address 33123 0
Room 2040, Level 2,
Darcy Rd,
Westmead Hospital
Westmead. NSW. 2145
Country 33123 0
Australia
Phone 33123 0
+612 92958474
Fax 33123 0
Email 33123 0
[email protected]
Contact person for public queries
Name 16370 0
Myra Fagan
Address 16370 0
Room 2040, Level 2,
Westmead Hospital
Darcy Rd,
Westmead. NSW. 2145
Country 16370 0
Australia
Phone 16370 0
+61298458089
Fax 16370 0
Email 16370 0
[email protected]
Contact person for scientific queries
Name 7298 0
Jenny Gunton
Address 7298 0
Room 2040, Level 2,
Westmead Hospital
Darcy Rd,
Westmead. NSW. 2145
Country 7298 0
Australia
Phone 7298 0
+61298458089
Fax 7298 0
Email 7298 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
no patients


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
No additional documents have been identified.