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: August 1, 2014
Last verified: August 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 with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken 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.
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Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken 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
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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 Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.

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 with/without stable doses of antihyperglycemic agent(s) taken 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 with/without stable doses of antihyperglycemic agent(s) taken 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 with/without stable doses of antihyperglycemic agent(s) taken 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 with/without stable doses of antihyperglycemic agent(s) taken 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 with/without stable doses of antihyperglycemic agent(s) taken 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 with/without stable doses of antihyperglycemic agent(s) taken 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     92/241     98/236     166/237     169/241     169/236  
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
phone: 1-800-526-7736


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Publications automatically indexed to this study:

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