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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
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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
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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 
Overall Participants Analyzed 
[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 ]

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
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Time Frame Adverse event data was collected for the duration of the study (104 weeks).
Additional Description The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm. MEDDRA 14.0 used for Week 26 results/ MEDDRA 16.0 used for Week 104 results.

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
Placebo: Baseline to Week 26 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. Data are presented for Baseline to Week 26.
Canagliflozin 100 mg: Baseline to Week 26 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. Data are presented for Baseline to Week 26.
Canagliflozin 300 mg: Baseline to Week 26 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. Data are presented for Baseline to Week 26.
Placebo: Baseline to Week 104 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. Data are presented for Baseline to Week 104.
Canagliflozin 100 mg: Baseline to Week 104 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. Data are presented for Baseline to Week 104
Canagliflozin 300 mg: Baseline to Week 104 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. Data are presented for Baseline to Week 104

Other Adverse Events
    Placebo: Baseline to Week 26   Canagliflozin 100 mg: Baseline to Week 26   Canagliflozin 300 mg: Baseline to Week 26   Placebo: Baseline to Week 104   Canagliflozin 100 mg: Baseline to Week 104   Canagliflozin 300 mg: Baseline to Week 104
Total, other (not including serious) adverse events             
# participants affected / at risk   99/237 (41.77%)   92/241 (38.17%)   98/236 (41.53%)   166/237 (70.04%)   169/241 (70.12%)   169/236 (71.61%) 
Gastrointestinal disorders             
Diarrhoea * 1             
# participants affected / at risk   14/237 (5.91%)   10/241 (4.15%)   11/236 (4.66%)   24/237 (10.13%)   14/241 (5.81%)   24/236 (10.17%) 
Constipation * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   8/237 (3.38%)   18/241 (7.47%)   13/236 (5.51%) 
Nausea * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   16/237 (6.75%)   11/241 (4.56%)   13/236 (5.51%) 
General disorders             
Oedema peripheral * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   17/237 (7.17%)   6/241 (2.49%)   2/236 (0.85%) 
Infections and infestations             
Influenza * 1             
# participants affected / at risk   5/237 (2.11%)   14/241 (5.81%)   9/236 (3.81%)   18/237 (7.59%)   25/241 (10.37%)   18/236 (7.63%) 
Nasopharyngitis * 1             
# participants affected / at risk   19/237 (8.02%)   23/241 (9.54%)   19/236 (8.05%)   36/237 (15.19%)   45/241 (18.67%)   44/236 (18.64%) 
Upper respiratory tract infection * 1             
# participants affected / at risk   11/237 (4.64%)   13/241 (5.39%)   10/236 (4.24%)   29/237 (12.24%)   23/241 (9.54%)   25/236 (10.59%) 
Urinary tract infection * 1             
# participants affected / at risk   9/237 (3.80%)   14/241 (5.81%)   17/236 (7.20%)   21/237 (8.86%)   32/241 (13.28%)   35/236 (14.83%) 
Bronchitis * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   8/237 (3.38%)   15/241 (6.22%)   11/236 (4.66%) 
Sinusitis * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   13/237 (5.49%)   9/241 (3.73%)   6/236 (2.54%) 
Vulvovaginal mycotic infection * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   1/237 (0.42%)   13/241 (5.39%)   11/236 (4.66%) 
Metabolism and nutrition disorders             
Hypoglycaemia * 1             
# participants affected / at risk   34/237 (14.35%)   25/241 (10.37%)   23/236 (9.75%)   47/237 (19.83%)   37/241 (15.35%)   36/236 (15.25%) 
Hyperglycaemia * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   19/237 (8.02%)   6/241 (2.49%)   6/236 (2.54%) 
Musculoskeletal and connective tissue disorders             
Arthralgia * 1             
# participants affected / at risk   12/237 (5.06%)   4/241 (1.66%)   5/236 (2.12%)   24/237 (10.13%)   21/241 (8.71%)   9/236 (3.81%) 
Back pain * 1             
# participants affected / at risk   8/237 (3.38%)   6/241 (2.49%)   12/236 (5.08%)   19/237 (8.02%)   24/241 (9.96%)   28/236 (11.86%) 
Muscle spasms * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   13/237 (5.49%)   4/241 (1.66%)   6/236 (2.54%) 
Pain in extremity * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   11/237 (4.64%)   16/241 (6.64%)   11/236 (4.66%) 
Nervous system disorders             
Headache * 1             
# participants affected / at risk   15/237 (6.33%)   8/241 (3.32%)   13/236 (5.51%)   25/237 (10.55%)   14/241 (5.81%)   22/236 (9.32%) 
Dizziness * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   13/237 (5.49%)   9/241 (3.73%)   6/236 (2.54%) 
Psychiatric disorders             
Insomnia * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   6/237 (2.53%)   5/241 (2.07%)   12/236 (5.08%) 
Renal and urinary disorders             
Pollakiuria * 1             
# participants affected / at risk   6/237 (2.53%)   6/241 (2.49%)   12/236 (5.08%)   10/237 (4.22%)   11/241 (4.56%)   15/236 (6.36%) 
Respiratory, thoracic and mediastinal disorders             
Cough * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   22/237 (9.28%)   17/241 (7.05%)   18/236 (7.63%) 
Oropharyngeal pain * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   15/237 (6.33%)   11/241 (4.56%)   7/236 (2.97%) 
Vascular disorders             
Hypertension * 1             
# participants affected / at risk   0/237 (0.00%)   0/241 (0.00%)   0/236 (0.00%)   12/237 (5.06%)   5/241 (2.07%)   7/236 (2.97%) 
* Events were collected by non-systematic assessment
1 Term from vocabulary, MEDDRA 14.0 / 16.0



  Limitations and Caveats
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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
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Vice President, Franchise Medical Leader, Cardiovascular & Metabolism Franchise
Organization: Janssen Research & Development, LLC
e-mail: ClinicalTrialDisclosure@its.jnj.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01106651     History of Changes
Other Study ID Numbers: CR017014
28431754DIA3010 ( Other Identifier: Janssen Research & Development, LLC )
Study First Received: April 1, 2010
Results First Received: April 1, 2013
Last Updated: October 27, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Ukraine: State Pharmacological Center - Ministry of Health