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Trial registered on ANZCTR


Registration number
ACTRN12618000982213
Ethics application status
Approved
Date submitted
4/06/2018
Date registered
12/06/2018
Date last updated
18/12/2018
Date data sharing statement initially provided
27/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to assess the safety and effectiveness of propagermanium as add-on therapy in Diabetic Kidney Disease (DKD) patients who are already taking Irbesartan
Scientific title
A Phase 2, Double-blind, Randomised, Placebo-Controlled, Crossover Study Evaluating the Safety and Efficacy of Propagermanium in Patients with Diabetic Kidney Disease (DKD) who are Receiving Irbesartan
Secondary ID [1] 295037 0
None
Universal Trial Number (UTN)
DMX-200-203
Trial acronym
Linked study record
This study is a follow up study to study ACTRN12614001132639

Health condition
Health condition(s) or problem(s) studied:
Diabetic Kidney Disease (DKD) 308069 0
Condition category
Condition code
Renal and Urogenital 307118 307118 0 0
Kidney disease
Metabolic and Endocrine 307234 307234 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Progagermanium one capsules orally twice daily for 12 weeks.
Irbesartan to be taken as per patient's usual routine.
Compliance will be measured by drug accountability and completion of a patient diary.
Patients will receive 12 weeks propagermanium and 12 weeks placebo separated by a 6 week washout period
Intervention code [1] 301372 0
Treatment: Drugs
Comparator / control treatment
Placebo one capsule orally twice a day for 12 weeks. The placebo capsules will be identical in appearance to propagermanium capsules and contain lactose monohydrate, magnesium stearate and talc.
Control group
Placebo

Outcomes
Primary outcome [1] 306071 0
To evaluate the change in albumin/creatinine ratio with adjunct use of propagermanium in patients with DKD who are receiving stable irbesartan. Assessed by monitoring of albumin/creatinine ratio.
Timepoint [1] 306071 0
35 week study duration. Will compare results from 12 weeks treatment with propagermanium to 12 weeks treatment with placebo (treatments are separated by a 6 week wash out period). Eleven 24-hour urine samples over the 35 week duration at Week -2, Week -1, Week 6, Week 11, Week 12, Week 18, Week 19, Week 25, Week 30, Week 31, Week 35.
Secondary outcome [1] 347471 0
To evaluate the effect of treatment with propagermanium on measures of kidney function by measuring estimated glomerular filtration rate.
Timepoint [1] 347471 0
Eleven 24-hour urine samples over the 35 week duration at Week -2, Week -1, Week 6, Week 11, Week 12, Week 18, Week 19, Week 25, Week 30, Week 31, Week 35.
Secondary outcome [2] 347692 0
To evaluate the safety of the adjunct use of propagermanium by assessment of adverse events. From previous clinical trials the following most frequently occurring adverse events included diarrhoea, headache, bruises from blood collection, elevated liver enzymes, general tiredness, decreased appetite, low creatinine (a chemical waste that indicates kidney function). low haemaglobin.
Adverse events will be recorded by a patient diary and by site staff during site visits at week -1, week 0, week 1, week 6, week 11, Week 12, week 18, week 19, week 20, week 25, week 30, week 31, week 35
Timepoint [2] 347692 0
35 week study duration. Safety assessed by monitoring adverse events. Assessed after screening and at week -1, week 0, week 1, week 6, week 11, Week 12, week 18, week 19, week 20, week 25, week 30, week 31, week 35
Secondary outcome [3] 347775 0
To evaluate the safety of the adjunct use of propagermanium by assessment of clinical laboratory tests (biochemistry, urinalysis, haematology). All results are reviewed by the investigator. Any out of range results that are deemed by the investigator to be clinically significant will be reported as an adverse event.
Biochemistry tests include:
Albumin, total protein, glucose, sodium, potassium, urea, creatinine, AST, ALT, alkaline phosphatase, gamma glutamyl transferase, high density lipoprotein (HDL), total bilirubin, triglyceride, total cholesterol, lactate dehydrogenase, calcium, uric acid and blood urea nitrogen
Timepoint [3] 347775 0
35 week study duration. Safety assessed by monitoring clinical laboratory tests (biochemistry, haematology, urinalysis). Assessed after screening and at week -1, week 0, week 1, week 6, week 11, Week 12, week 18, week 19, week 20, week 25, week 30, week 31, week 35
Secondary outcome [4] 347776 0
To evaluate the effect of treatment with propagermanium on measures of proteinuria by the measuring albumin/creatinine ratio.
Timepoint [4] 347776 0
Eleven 24-hour urine samples over the 35 week duration at Week -2, Week -1, Week 6, Week 11, Week 12, Week 18, Week 19, Week 25, Week 30, Week 31, Week 35.

Eligibility
Key inclusion criteria
1. Aged 18 to 80 (inclusive) at screening;
2. A diagnosis of type 2 diabetes mellitus;
3. Baseline HbA1c between 42 to 97 mmol/mol (6 to 11%);
4. Fasting plasma glucose less than or equal to 15 mmol/L;
5. Must be receiving a stable dose of 300 mg daily of irbesartan (in any marketed formulation) for at least 3 months prior to screening, and have no plan to change treatment regime throughout the study;
6. Patients can be on stable doses of angiotensin converting enzyme inhibitors, aldosterone inhibitors, and/or sodium-glucose co-transporter-2 inhibitors. However, the dose and regimen must be stable for 3 months prior to screening and must have no plan to change treatment regime throughout the study;
7. Mean of two ACR values (screening and baseline) of more than or equal to 30-500 mg/mmol and within 30% of the screening value at the baseline assessment;
8. Estimated GFR more than or equal to 25-90 mL/min/1.73 m2 using chronic kidney disease epidemiology collaboration (CKD-EPI) formula at screening;
9. Serum potassium levels (screening and baseline) less than 5.5 mmol/l. If either value is 5.5 or above the patient may receive dietary advice and be retested one week after the second value;
10. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not of childbearing potential, defined as surgically sterile (documented hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or postmenopausal (no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone [FSH] level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.);
• Of childbearing potential and agrees to use a highly effective method of contraception consistently during the treatment period and for at least 60 days after the last dose of investigational product;
11. A male patient with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception during the treatment period and for at least 60 days after the last dose of investigational product and refrains from donating sperm during this period;
12. Have given written informed consent prior to any study procedures being performed.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. A history of type 1 diabetes mellitus;
2. Known non-diabetic renal disease including prior kidney transplant;
3. A prior organ or stem cell transplant;
4. A major adverse cardiac event within 6 months before screening;
5. Patients receiving immunosuppressive medications including prednisone;
6. Rapid eGFR decline with renal replacement likely during study
7. Lymphoma, leukaemia, or any malignancy within the past 5 years except for basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ that have been resected with no evidence of metastatic disease for 3 years;
8. Jaundice, active hepatitis, or known hepatobiliary disease (except asymptomatic cholelithiasis);
9. Alanine aminotransferase and/or aspartate aminotransferase more than two times the upper limit of normal at screening;
10. Participation in any clinical study with an experimental medication or device within 90 days or 5 half-lives (whichever is longer) of screening or have previously participated in a study involving propagermanium;
11. Positive screening assessment for viral hepatitis B surface antigen or hepatitis C virus (HCV) antibody AND positive HCV RNA or human immunodeficiency virus (HIV);
12. Seated blood pressure of more than or equal to 165/105 mmHg at screening;
13. Body mass index more than or equal to 40 kg/m2 at screening;
14. Active treatment for a major depressive disorder, or past hospitalisation for a major
depressive episode;
15. Is breast feeding or pregnant;
16. Unable to comply with the study procedures and assessments, including the ability swallow the study treatment capsules;
17. Any other disease, physical or psychological condition that the investigator or sponsor believes may contraindicate the use of the investigational medicinal product or affect the interpretation of study results or render the patient at high risk from treatment complications;
19. Are investigator site personnel directly affiliated with this study and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
None
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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,QLD,VIC
Recruitment hospital [1] 11013 0
Simon Roger Gosford Renal Research - Gosford
Recruitment hospital [2] 11064 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 11847 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 11848 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [5] 11849 0
Liverpool Hospital - Liverpool
Recruitment hospital [6] 11850 0
Westmead Hospital - Westmead
Recruitment hospital [7] 11851 0
Sunshine Hospital - St Albans
Recruitment hospital [8] 11852 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [9] 11853 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [10] 11854 0
Epworth Richmond - Richmond
Recruitment postcode(s) [1] 22804 0
2250 - Gosford
Recruitment postcode(s) [2] 22866 0
3084 - Heidelberg
Recruitment postcode(s) [3] 23985 0
3128 - Box Hill
Recruitment postcode(s) [4] 23986 0
3121 - Richmond
Recruitment postcode(s) [5] 23987 0
4575 - Birtinya
Recruitment postcode(s) [6] 23988 0
2170 - Liverpool
Recruitment postcode(s) [7] 23989 0
2145 - Westmead
Recruitment postcode(s) [8] 23990 0
3021 - St Albans
Recruitment postcode(s) [9] 23991 0
2065 - Royal North Shore Hospital
Recruitment postcode(s) [10] 23992 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 299617 0
Commercial sector/Industry
Name [1] 299617 0
Dimerix Ltd
Address [1] 299617 0
Dimerix Ltd, 425 Smith St, Fitzroy VIC 3065
Country [1] 299617 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Dimerix Ltd
Address
Dimerix Ltd, 425 Smith St, Fitzroy VIC 3065
Country
Australia
Secondary sponsor category [1] 298939 0
None
Name [1] 298939 0
None
Address [1] 298939 0
NA
Country [1] 298939 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300520 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 300520 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 300520 0
Australia
Date submitted for ethics approval [1] 300520 0
13/06/2018
Approval date [1] 300520 0
16/07/2018
Ethics approval number [1] 300520 0
Ethics committee name [2] 300567 0
Austin Health Human Research Ethics Committee
Ethics committee address [2] 300567 0
145 Studley Rd
Heidelburg VIC 3084
Ethics committee country [2] 300567 0
Australia
Date submitted for ethics approval [2] 300567 0
11/07/2018
Approval date [2] 300567 0
15/08/2018
Ethics approval number [2] 300567 0

Summary
Brief summary
Eligible patients will randomly assigned (50/50 chance) to receive both the propagermanium and placebo in different orders as follows, either:
1. Treatment Period 1: Propagermanium capsule twice a day for 12 weeks
Treatment Period 2: Placebo capsule twice a day for 12 weeks.
OR
2. Treatment Period 1: Placebo capsule twice a day for 12 weeks
Treatment Period 2: Propagermanium capsule twice a day for 12 weeks.

This study will determine how safe and effective propagermanium is in the treatment of paients with DKD by:
• monitoring symptoms that patients may experience while on the study
• measuring levels of protein in patients urine and kidney function during the course of the study.
• measuring the levels of propagermanium and irbesartan that enters into patients urine and blood
• comparing the propagermanium result to patients' pre-study and placebo results
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83926 0
Dr Simon Roger
Address 83926 0
Gosford Renal Research,
Level 1/ 37 William Street,
Gosford New South Wales 2250
Country 83926 0
Australia
Phone 83926 0
+61 (0)2 4323 7977
Fax 83926 0
Email 83926 0
sdroger@bigpond.net.au
Contact person for public queries
Name 83927 0
Ms Alisha Smith
Address 83927 0
Dimerix Ltd, 425 Smith St, Fitzroy, VIC 3065
Country 83927 0
Australia
Phone 83927 0
+61 1300 813 321
Fax 83927 0
Email 83927 0
alisha.smith@dimerix.com
Contact person for scientific queries
Name 83928 0
Dr Robert Shepherd
Address 83928 0
Dimerix Ltd, 425 Smith St, Fitzroy, VIC 3065
Country 83928 0
Australia
Phone 83928 0
+61 1300 813 321
Fax 83928 0
Email 83928 0
robert.shepherd@dimerix.com

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
No Results