Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Safety and Efficacy Study of Canagliflozin in Older Patients (55 to 80 Years of Age) With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01106651
First received: April 1, 2010
Last updated: October 27, 2014
Last verified: October 2014
Results First Received: April 1, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Canagliflozin 100 mg
Drug: Canagliflozin 300 mg
Drug: Antihyperglycemic agent(s)
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study evaluated the efficacy and safety of canagliflozin in older patients with type 2 diabetes mellitus with inadequate control on their current diabetes treatment regimen. The study began on 07 June 2010 and ended on 23 May 2013. Patients were recruited from 90 study centers located in 17 countries worldwide.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
716 patients were randomly allocated to the 3 treatment arms. 714 patients received at least 1 dose of study drug and were included in the modified intent-to-treat (mITT) analysis set and safety analysis set. Participant flow is presented for Baseline to Week 104 (Overall Study).

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks in addition to being on a stable antihyperglycemic (AHA) regimen at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks in addition to being on a stable antihyperglycemic (AHA) regimen at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks in addition to being on a stable antihyperglycemic (AHA) regimen at the time of study entry.

Participant Flow:   Overall Study
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
STARTED     237     241     236  
COMPLETED     158     184     178  
NOT COMPLETED     79     57     58  
Adverse Event                 17                 9                 23  
Lost to Follow-up                 8                 2                 6  
Physician Decision                 4                 3                 1  
Protocol Violation                 1                 2                 1  
Withdrawal by Subject                 14                 7                 4  
Noncompliance with study drug                 1                 0                 2  
Not specified                 34                 31                 21  
Death                 0                 3                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks in addition to being on a stable antihyperglycemic (AHA) regimen at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks in addition to being on a stable antihyperglycemic (AHA) regimen at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks in addition to being on a stable antihyperglycemic (AHA) regimen at the time of study entry.
Total Total of all reporting groups

Baseline Measures
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg     Total  
Number of Participants  
[units: participants]
  237     241     236     714  
Age  
[units: participants]
       
<=18 years     0     0     0     0  
Between 18 and 65 years     151     141     149     441  
>=65 years     86     100     87     273  
Age  
[units: years]
Mean ± Standard Deviation
  63.2  ± 6.21     64.3  ± 6.46     63.4  ± 5.99     63.6  ± 6.24  
Gender  
[units: participants]
       
Female     94     117     107     318  
Male     143     124     129     396  
Region of Enrollment  
[units: participants]
       
AUSTRALIA     6     6     11     23  
CANADA     24     32     28     84  
COLOMBIA     18     15     20     53  
FRANCE     2     2     3     7  
GREECE     1     1     1     3  
HONG KONG     1     1     2     4  
INDIA     8     3     11     22  
NEW ZEALAND     16     10     11     37  
POLAND     11     12     14     37  
ROMANIA     8     10     7     25  
SOUTH AFRICA     9     12     10     31  
SPAIN     2     3     8     13  
SWEDEN     4     4     2     10  
SWITZERLAND     2     2     0     4  
UKRAINE     3     8     3     14  
UNITED KINGDOM     19     22     8     49  
UNITED STATES     103     98     97     298  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change in HbA1c From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

2.  Secondary:   Percentage of Patients With HbA1c <7% at Week 26   [ Time Frame: Week 26 ]

3.  Secondary:   Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

4.  Secondary:   Percent Change in Body Weight From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

5.  Secondary:   Change in Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition   [ Time Frame: Day 1 (Baseline) and Week 26 ]

6.  Secondary:   Change in Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition   [ Time Frame: Day 1 (Baseline) and Week 26 ]

7.  Secondary:   Change in Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition   [ Time Frame: Day 1 (Baseline) and Week 26 ]

8.  Secondary:   Change in Systolic Blood Pressure (SBP) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

9.  Secondary:   Percent Change in Triglycerides From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

10.  Secondary:   Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]
  Hide Outcome Measure 10

Measure Type Secondary
Measure Title Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
Measure Description The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 or each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks in addition to being on a stable antihyperglycemic (AHA) regimen at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks in addition to being on a stable antihyperglycemic (AHA) regimen at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks in addition to being on a stable antihyperglycemic (AHA) regimen at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  206     225     222  
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26  
[units: Percent┬áchange]
Least Squares Mean ± Standard Error
  1.5  ± 1.2     6.8  ± 1.2     6.2  ± 1.2  


Statistical Analysis 1 for Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] 5.3
Standard Error of the mean ± 1.4
95% Confidence Interval ( 2.6 to 7.9 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] 4.7
Standard Error of the mean ± 1.4
95% Confidence Interval ( 2.0 to 7.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



11.  Secondary:   Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

12.  Secondary:   Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

13.  Secondary:   Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

14.  Secondary:   Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information