A Efficacy, Safety, and Tolerability Study of Canagliflozin in Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Alone or in Combination With a Sulphonylurea

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01381900
First received: June 23, 2011
Last updated: April 23, 2014
Last verified: April 2014
Results First Received: November 21, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Placebo
Drug: Canagliflozin 100mg
Drug: Canagliflozin 300mg
Drug: Metformin
Drug: Sulphonylurea

  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 Asian participants with type 2 diabetes mellitus who had inadequate glycemic control on a maximally effective or tolerated dose of metformin alone or metformin plus sulphonylurea (SU). It was conducted between 30 June 2011 and 21 December 2012 and recruited patients from 36 sites.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study had two background treatment strata: 331 participants in the metformin alone stratum and 347 in the metformin plus SU. In total, 678 participants were randomly allocated to the 3 treatment arms, 676 received at least 1 dose of study drug and were included in the modified intent-to-treat (mITT) analysis set and the safety analysis set.

Reporting Groups
  Description
Placebo Each participant received matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Canagliflozin 100 mg Each participant received 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Canagliflozin 300 mg Each participant received 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.

Participant Flow:   Overall Study
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
STARTED     226     223     227  
COMPLETED     217     214     215  
NOT COMPLETED     9     9     12  
Subject meets glycemic withdrawal crit.                 2                 0                 0  
Adverse Event                 4                 6                 7  
Noncompliance with study drug                 0                 0                 1  
Physician Decision                 0                 1                 1  
Protocol Violation                 0                 1                 1  
Withdrawal by Subject                 0                 0                 1  
Early withdraw                 3                 1                 1  



  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 participant received matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Canagliflozin 100 mg Each participant received 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Canagliflozin 300 mg Each participant received 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Total Total of all reporting groups

Baseline Measures
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg     Total  
Number of Participants  
[units: participants]
  226     223     227     676  
Age  
[units: participants]
       
<=18 years     0     0     0     0  
Between 18 and 65 years     184     187     186     557  
>=65 years     42     36     41     119  
Age  
[units: years]
Mean ± Standard Deviation
  55.8  ± 9.35     56.5  ± 8.25     56.4  ± 9.21     56.3  ± 8.94  
Gender  
[units: participants]
       
Female     101     99     114     314  
Male     125     124     113     362  
Region Enroll  
[units: participants]
       
China     213     210     213     636  
Malaysia     3     5     4     12  
Vietnam     10     8     10     28  



  Outcome Measures
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1.  Primary:   Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 18   [ Time Frame: Day 1 (Baseline) and Week 18 ]

2.  Secondary:   Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18   [ Time Frame: Day 1 (Baseline) and Week 18 ]

3.  Secondary:   Percent Change in Body Weight From Baseline to Week 18   [ Time Frame: Day 1 (Baseline) and Week 18 ]

4.  Secondary:   Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <7% at Week 18   [ Time Frame: Day 1 (Baseline) and Week 18 ]

5.  Secondary:   Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <6.5% at Week 18   [ Time Frame: Day 1 (Baseline) and Week 18 ]


  Serious Adverse Events
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Time Frame Adverse event data were collected for the duration of the study, consisting of an 18-week double-blind treatment phase and a 4-week follow-up period.
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 of the treatment arms during the study.

Reporting Groups
  Description
Placebo Each participant received matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Canagliflozin 100 mg Each participant received 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Canagliflozin 300 mg Each participant received 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.

Serious Adverse Events
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Total, serious adverse events        
# participants affected / at risk     4/226 (1.77%)     5/223 (2.24%)     4/227 (1.76%)  
Cardiac disorders        
Atrial flutter † 1      
# participants affected / at risk     0/226 (0.00%)     0/223 (0.00%)     1/227 (0.44%)  
Infections and infestations        
Appendicitis † 1      
# participants affected / at risk     0/226 (0.00%)     0/223 (0.00%)     1/227 (0.44%)  
Lung infection † 1      
# participants affected / at risk     0/226 (0.00%)     0/223 (0.00%)     1/227 (0.44%)  
Pneumonia † 1      
# participants affected / at risk     1/226 (0.44%)     0/223 (0.00%)     1/227 (0.44%)  
Tracheitis † 1      
# participants affected / at risk     0/226 (0.00%)     1/223 (0.45%)     0/227 (0.00%)  
Injury, poisoning and procedural complications        
Spinal compression fracture † 1      
# participants affected / at risk     0/226 (0.00%)     1/223 (0.45%)     0/227 (0.00%)  
Metabolism and nutrition disorders        
Hypoglycaemia † 1      
# participants affected / at risk     0/226 (0.00%)     0/223 (0.00%)     1/227 (0.44%)  
Musculoskeletal and connective tissue disorders        
Intervertebral disc protrusion † 1      
# participants affected / at risk     0/226 (0.00%)     1/223 (0.45%)     0/227 (0.00%)  
Rotator cuff syndrome † 1      
# participants affected / at risk     0/226 (0.00%)     1/223 (0.45%)     0/227 (0.00%)  
Nervous system disorders        
Cerebral infarction † 1      
# participants affected / at risk     1/226 (0.44%)     0/223 (0.00%)     0/227 (0.00%)  
Neuritis † 1      
# participants affected / at risk     1/226 (0.44%)     0/223 (0.00%)     0/227 (0.00%)  
Neuropathy peripheral † 1      
# participants affected / at risk     1/226 (0.44%)     0/223 (0.00%)     0/227 (0.00%)  
Transient ischaemic attack † 1      
# participants affected / at risk     0/226 (0.00%)     1/223 (0.45%)     0/227 (0.00%)  
Respiratory, thoracic and mediastinal disorders        
Bronchiectasis † 1      
# participants affected / at risk     1/226 (0.44%)     0/223 (0.00%)     0/227 (0.00%)  
Events were collected by systematic assessment
1 Term from vocabulary, MEDDRA 15.1




  Other Adverse Events


  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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