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.
No text entered.

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 ]
  Hide Outcome Measure 5

Measure Type Secondary
Measure Title Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <6.5% at Week 18
Measure Description The table below shows the percentage of patients with HbA1c <6.5% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.
Time Frame Day 1 (Baseline) and Week 18  
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 overall mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 18 values. Table includes only participants with both baseline and post baseline values.

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.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  226     223     227  
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <6.5% at Week 18  
[units: Percentage¬†of¬†patients]
  11.7     21.6     25.3  


Statistical Analysis 1 for Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <6.5% at Week 18
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] Regression, Logistic
Odds Ratio (OR) [3] 2.55
95% Confidence Interval ( 1.45 to 4.48 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
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[2] Other relevant method information, such as adjustments or degrees of freedom:
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[3] Other relevant estimation information:
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Statistical Analysis 2 for Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <6.5% at Week 18
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] Regression, Logistic
Odds Ratio (OR) [3] 3.29
95% Confidence Interval ( 1.88 to 5.75 )
[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] Other relevant estimation information:
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  Serious Adverse Events


  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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  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 Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Vice President, Franchise Medical Leader, Cardiovascular & Metabolism Franchise
Organization: Janssen Research & Development, LLC
phone: 1-800-526-7736


No publications provided


Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01381900     History of Changes
Other Study ID Numbers: CR018541, 28431754DIA3014
Study First Received: June 23, 2011
Results First Received: November 21, 2013
Last Updated: April 23, 2014
Health Authority: United States: Institutional Review Board