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Trial registered on ANZCTR


Registration number
ACTRN12610000194066
Ethics application status
Approved
Date submitted
23/02/2010
Date registered
4/03/2010
Date last updated
30/08/2024
Date data sharing statement initially provided
30/08/2024
Date results information initially provided
30/08/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised Double-Blind Placebo-Controlled Multicenter Study with Extension to Evaluate the Efficacy Safety and Tolerability of Canagliflozin in the Treatment of Subjects with Type 2 Diabetes
Mellitus Who Have Moderate Renal Impairment
Scientific title
A Randomised Double-Blind Placebo-Controlled Multicenter Study with Extension to Evaluate the Efficacy Safety and Tolerability of Canagliflozin in the Treatment of Subjects with Type 2 Diabetes
Mellitus Who Have Moderate Renal
Secondary ID [1] 1457 0
NCT01064414 (issuing authority ClinicalTrials.gov)
Universal Trial Number (UTN)
Trial acronym
DIA3004
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes in patietns with moderate renal impairment. 256865 0
Condition category
Condition code
Metabolic and Endocrine 257013 257013 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Canagliflozin (JNJ-28431754) oral capsule, daily dose either 100mg or 300mg. Dose will be assigned randomly.

Canagliflozin against placebo in treating patients over 25 years of age, who have inadequately controlled type 2 diabetes and moderate renal impairment. Patients will be randomised to receive either 100mg or 300mg of canagliflozin or placebo for 26 weeks, in addition to their current diabetes medication, with an extension of 26 weeks.Total treatment phase is 52 weeks. Study drug and placebo will be tablet form and taken orally.
Intervention code [1] 256059 0
Treatment: Drugs
Comparator / control treatment
Placebo, looks like study drug but is a sugar pill.
Control group
Placebo

Outcomes
Primary outcome [1] 257907 0
To assess the effect of canagliflozin relative to placebo on glycated hemoglobin (HbA1c). HbA1c is a test that measures the amount of glycated hemoglobin in the blood.
Timepoint [1] 257907 0
After 26 weeks of treatment
Primary outcome [2] 257908 0
To assess safety and tolerability, by assessing adverse events during the duration of the trial and proportion of subjects receiving rescue therapy and time to rescue therapy. Important measures of renal safety will be the eGFR, based upon serum creatinine, and Albumin Creatinin Ratio (ACR) measured in the first morning urine collection
Timepoint [2] 257908 0
After 26 weeks of treatment
Secondary outcome [1] 263372 0
Fasting plasma glucose (FPG) will be assessed via blood analysis.
Timepoint [1] 263372 0
After 26 weeks of treatment
Secondary outcome [2] 263373 0
Proportion of subjects with an HbA1c<7% will be assessed via blood analysis.
Timepoint [2] 263373 0
After 26 and 52 weeks of treatment
Secondary outcome [3] 263374 0
Systolic and diastolic blood pressure will be measured using a manometer.
Timepoint [3] 263374 0
After 26 and 52 weeks of treatment
Secondary outcome [4] 263375 0
Proportion of subjects receiving rescue therapy and time to rescue therapy. From Day 1 to Week 26, glycemic rescue therapy will be implemented in subjects with
FPG values, repeated and confirmed (repeated within 7 days), meeting progressively stricter Fasting Plasma Glucose (FPG) criteria. After
Week 26, HbA1c will be used to determine the need for rescue therapy. In this study,
glycemic rescue therapy will be selected and managed, as considered clinically
appropriate, by the investigator.
Timepoint [4] 263375 0
After 26 and 52 weeks of treatment
Secondary outcome [5] 263376 0
Fasting plasma lipids will be measured via blood analysis.
Timepoint [5] 263376 0
After 26 and 52 weeks of treatment
Secondary outcome [6] 263377 0
Body weight will be assessed using a claibrated scale.
Timepoint [6] 263377 0
After 26 and 52 weeks of treatment
Secondary outcome [7] 263378 0
Renal function estimated glomerular filtration rate (eGFR) and albumin creatinin ration (ACR). The eGFR, based upon serum creatinine, and ACR measured in the first morning urine collection (for both measures, using the mean
of 2 determinations: 1 performed on the day prior to the visit and 1 on the visit day). The eGFR will be calculated based on the 4-variable formula according to the Modification of Diet in Renal Disease (MDRD) study with the correction for the standardized creatinine method.
The MDRDequation includes serum creatinine, age, gender, and race which all are important ovariates affecting GFR as assessed by the direct method.
Timepoint [7] 263378 0
After 26 and 52 weeks of treatment

Eligibility
Key inclusion criteria
1) Man or woman with Type 2 diabetes Mellitus (T2DM), age =25 years, and either not on an anti hyperglycemic agent (AHA) or on any AHA in monotherapy or combination therapy (including oral or non-oral agents).
2) HbA1c =7.0% to =10.5% at screening and Week -2 visits.
3) On a stable AHA regimen consistent with local prescribing information (ie, local
label[s]) for at least 8 weeks (and 12 weeks for peroxisome proliferator-activated receptors (PPAR) agents [eg, rosiglitazone or pioglitazone]) before Week -2.
4) Have moderate renal impairment, as defined by eGFR values (estimated by the
4-variable Modification of Diet in Renal Disease (MDRD) equation) =30 and <50 mL/min/1.73 m2 at both the screening and
the Week -2 visit, with generally stable renal function, as demonstrated by =25%
decline in eGFR at Week-2 relative to the screening visit value
5) Fasting plasms glucose (FPG) =270 mg/dL (15 mmol/L) at
Week-2
6) Site fasting fingerstick glucose of =110 mg/dL (6.1 mmol/L) and =270 mg/dL
(15 mmol/L) on Day 1
Women must be on a highly effictive method of birth control
7) Women of childbearing potential must have a negative urine beta-human chorionic
gonadotropin (beta-hCG) pregnancy test at screening and baseline (predose, Day 1).
8) Willing and able to adhere to the prohibitions and restrictions specified in this
protocol.
9) Subjects must have signed an informed consent document indicating that they
understand the purpose of and procedures required for the study and are willing to
participate in the study.
10) To participate in the optional pharmacogenomic component of this study, subjects must have signed the informed consent form for pharmacogenomic research
indicating willingness to participate in the pharmacogenomic component of the study
(where local regulations permit). Refusal to give consent for this component does not
exclude a subject from participation in the clinical study.
11) Adequate compliance with the run-in period study procedures, including performance of the self monitored blood glucose (SMBG) measurements (completed at least 3 or more SMBG measurements per week) with appropriate diary entries, and =80% compliance (by pill count) with single-blind placebo capsules.
Minimum age
25 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta-cell transplantation, or
diabetes secondary to pancreatitis or pancreatectomy
2) Repeated (ie, 2 or more over a 1-week period) FPG and/or fasting SMBG glucose
measurements >270 mg/dL (15 mmol/L) during the pretreatment phase, despite
reinforcement of diet and exercise counseling
3) Have proliferative diabetic retinopathy for which treatment is planned during the
course of the study
4) History of 1 or more severe hypoglycemic episode within 6 months before screening.
5) History of hereditary glucose-galactose malabsorption or primary renal glucosuria
6) Ongoing, inadequately controlled thyroid disorder (eg, subject has a known thyroid
stimulating hormone [TSH] value that is either <0.2 or >10 mIU/L)
7) Ongoing eating disorder or significant weight loss or weight gain within 12 weeks,
defined as an increase or decrease of 5% in body weight based upon clinic-based
measurement or, if not available, subject report
8) Renal disease that required treatment with immunosuppressive therapy or a history of dialysis or renal transplant
9) Presence of nephrotic syndrome (eg, severe proteinuria with hypoalbuminemia and/or edema), or inflammatory renal disease (eg, acute interstitial nephritis, acute or rapidly-progressive glomerulonephritis)
10) Subject is likely to require dialysis or transplantation during participation in the study
11) Myocardial infarction, unstable angina, revascularization procedure (eg, stent or
bypass graft surgery), or cerebrovascular accident within 3 months before screening,
or revascularization procedure is planned, or subject has a history of New York Heart
12) Association (NYHA) Class III-IV cardiac disease (refer to Attachment 3, New York
Heart Association Classification of Cardiac Disease, for a description of the classes)
13) Findings on 12-lead ECG that would require urgent diagnostic evaluation or
intervention (eg, new clinically important arrhythmia or conduction disturbance)
14) Uncontrolled hypertension (ie, using an average of 3 seated blood pressure readings with a diastolic blood pressure =100 mmHg or systolic blood pressure =160 mmHg) at Week -2
15) History of hepatitis B surface antigen or hepatitis C antibody positive (unless associated with documented persistently stable/normal range aspartate
aminotransferase [AST] and Alanine Transaminase (ALT) levels, or other clinically active liver disease
16) History of prior bariatric surgical procedure within 3 years before the screening visit
17) Fasting serum triglycerides =600 mg/dL (6.74 mmol/L) at screening (or subsequent
visit if not fasting at screening)
18) Alanine aminotransferase level >2.0 times the upper limit of normal (ULN) or total bilirubin >1.5 times the ULN at screening (for elevations in bilirubin: if, in the opinion of the investigator and agreed upon by the sponsor’s medical officer, the elevation in bilirubin is consistent with Gilbert’s disease, the subject may participate)
19) Hemoglobin concentration <10 g/L at screening
20) History of malignancy within 5 years before screening (exceptions: squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or a malignancy that in the opinion of the investigator, with concurrence with the sponsor’s medical monitor, is considered cured with minimal risk of recurrence)
21) Clinically important hematologic disorder (eg, symptomatic anemia, proliferative bone marrow disorder, thrombocytopenia)
22) History of human immunodeficiency virus (HIV) antibody positive
23) Investigator’s assessment that the subject’s life expectancy is less than 1 year
24) Any condition that in the opinion of the investigator would make participation not in
the best interest of the subject, or could prevent, limit, or confound the protocol-specified assessments
25) Major surgery (ie, requiring general anesthesia) within 12 weeks before screening, or subject has not fully recovered from surgery, or planned surgery during time the subject is expected to participate in the study
26) Any other sodium glucose transporter 2 (SGLT2) inhibitor
27) Colesevelam and bromocriptine
28) Subjects receiving anti-hypertensive or anti-hyperlipidemic therapy not on a stable
regimen (same medication and dose[s]) for at least 4 weeks before Day 1
29) Known allergies, hypersensitivity, or intolerance to canagliflozin or its excipients
30) Current use of a corticosteroid medication or immunosuppressive agent, or likely to require treatment with a corticosteroid medication (for longer than 2 weeks in duration) or an immunosuppressive agent
31) Subject currently treated with or who are likely to require treatment with a
non-steroidal anti-inflammatory drug (NSAID) in higher doses during their expected participation in the study
32) Received an investigational drug (including vaccines), other than a placebo agent, or used an investigational medical device within 3 months before the planned start of reatment or received at least 1 dose of canagliflozin in a prior study
33) History of drug or alcohol abuse within 3 years before screening
34) Pregnant or breast-feeding or planning to become pregnant or breast-feed during the study
35) Employees of the investigator or study site, with direct involvement in the proposed
study or other studies under the direction of that investigator or study site, as well as
family members of the employees or the investigator

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)
Subjects will be randomised via interactive voice response system (IVRS) in equal numbers into the 3 treatment arms.This is done by a central randomisation via phone assigning treatmetn number to the patietn which are replected ojn the medication kits.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Treatmetn, Ransdomised, Double Blind, Parallel Group Assignment, Safety Study, active-comperator, multi-centre study
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/04/2010
Actual
7/06/2010
Date of last participant enrolment
Anticipated
Actual
23/06/2011
Date of last data collection
Anticipated
Actual
2/08/2012
Sample size
Target
240
Accrual to date
Final
272
Recruitment outside Australia
Country [1] 2505 0
New Zealand
State/province [1] 2505 0
Country [2] 2506 0
India
State/province [2] 2506 0
Country [3] 2507 0
Korea, Democratic People's Republic Of
State/province [3] 2507 0
Country [4] 2508 0
Belgium
State/province [4] 2508 0
Country [5] 2509 0
France
State/province [5] 2509 0
Country [6] 2510 0
Germany
State/province [6] 2510 0
Country [7] 2511 0
Italy
State/province [7] 2511 0
Country [8] 2512 0
Latvia
State/province [8] 2512 0
Country [9] 2513 0
Romania
State/province [9] 2513 0
Country [10] 2514 0
Russian Federation
State/province [10] 2514 0
Country [11] 2515 0
Spain
State/province [11] 2515 0
Country [12] 2516 0
Brazil
State/province [12] 2516 0
Country [13] 2517 0
Mexico
State/province [13] 2517 0
Country [14] 2518 0
Canada
State/province [14] 2518 0
Country [15] 2519 0
United States of America
State/province [15] 2519 0

Funding & Sponsors
Funding source category [1] 256564 0
Commercial sector/Industry
Name [1] 256564 0
Johnson& Johnson Pharmaceutical Research & Development, LLC
Country [1] 256564 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Johnson& Johnson Pharmaceutical Research & Development, LLC
Address
Global Communications
Mailstop E1756
920 Route 202
Raritan, NJ 08869
Country
United States of America
Secondary sponsor category [1] 255860 0
Commercial sector/Industry
Name [1] 255860 0
Janssen-Cilag PTY LTD
Address [1] 255860 0
1-5 Khartoum Road, North Ryde, NSW 2113
Country [1] 255860 0
Australia
Other collaborator category [1] 1138 0
Commercial sector/Industry
Name [1] 1138 0
Janssen-Cilag (New Zealand) Limited
Address [1] 1138 0
105 Carlton Gore Road, Newmarket, Auckland
Country [1] 1138 0
New Zealand

Ethics approval
Ethics application status
Approved

Summary
Brief summary
The study aims to compare 2 doses of canagliflozin against placebo in treating patients over 25 years of age, who have inadequately controlled type 2 diabetes and moderate renal impairment. Patients will be randomised to receive either 100mg or 300mg of canagliflozin or placebo for 26 weeks, in addition to their current diabetes medication, with a possibility of continuing for an additional 26 weeks. The study is blinded so neither the patients nor the site
staff will know what the patient is taking and there is an equal change of receiving the different doses of canagliflozin or placebo. The study will asses patients for how well their diabetes is controlled on the study and also assess any side effects they have whilst taking study medication. In order to achieve this patients will have to attend regular clinic visits intially every
3 weeks then 6 - 8 weekly for first 26 weeks. In the second 26 weeks there are only 2 visits 18 weeks apart. During these visits blood samples will be taken and analaysed and patients will be asked how they feel and this will all be recorded on a case report form. Patients will also be
asked to complete a diary during the study, recording their blood sugar levels (taken on a monitor provided by the sponsor), any problems they have between visits and when they take their study medication.
Trial website
www.ClinicalTrials.gov
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30867 0
Address 30867 0
Country 30867 0
Phone 30867 0
Fax 30867 0
Email 30867 0
Contact person for public queries
Name 14114 0
Tracy Watt
Address 14114 0
Associated Director Global Clinical Operations
Janssen-Cilag Australia – New Zealand
1-5 Karthoum Road
North Ryde
NSW 2113
Country 14114 0
Australia
Phone 14114 0
+61 2 8875 3347
Fax 14114 0
+61 2 9888 9346
Email 14114 0
[email protected]
Contact person for scientific queries
Name 5042 0
Keith Usiskin
Address 5042 0
920 Route 201
POB 300
Raritan, NJ 88869
Country 5042 0
United States of America
Phone 5042 0
+1 908 704 5654
Fax 5042 0
+1 908 753 8564
Email 5042 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
When will data be available (start and end dates)?
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
Available to whom?
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
Available for what types of analyses?
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
How or where can data be obtained?
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23171Other https://clinicaltrials.gov/ct2/show/results/NCT01064414?term=NCT01064414&draw=2&rank=1&view=results 
23816Other    Link to results posted in ClinicalTrials.gov



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
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