A Study to Evaluate the Effectiveness, Safety, and Tolerability of Canagliflozin in Combination With Metformin in the Treatment of Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control With Diet and Exercise

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01809327
First received: March 8, 2013
Last updated: December 1, 2015
Last verified: November 2015
Results First Received: December 1, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Canagliflozin 100 mg
Drug: Canagliflozin 300 mg
Drug: Metformin XR

  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
The study was conducted between 16 May 2013 and 01 December 2014 and recruited participants from 158 study centers in 12 countries worldwide.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 1,186 participants were randomly allocated to the 5 treatment arms. All participants received at least 1 dose of study drug and were included in the modified intent-to-treat (mITT) analysis set.

Reporting Groups
  Description
Metformin XR Participants received metformin extended release (XR) tablets (in doses titrated over 9 weeks) once daily with the evening meal, plus one placebo capsule before the morning meal and one placebo capsule with the evening meal (to match the canagliflozin capsules administered in other treatment arms) for 26 weeks.
Canagliflozin 100 Milligram (mg) Participants received one 100 milligram (mg) canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks.
Canagliflozin 300 mg Participants received one 300 mg canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks.
Canagliflozin 100 mg + Metformin XR Participants received one 100 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.
Canagliflozin 300 mg + Metformin XR Participants received one 300 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.

Participant Flow:   Overall Study
    Metformin XR     Canagliflozin 100 Milligram (mg)     Canagliflozin 300 mg     Canagliflozin 100 mg + Metformin XR     Canagliflozin 300 mg + Metformin XR  
STARTED     237     237     238     237     237  
COMPLETED     205     211     216     225     212  
NOT COMPLETED     32     26     22     12     25  
Lost to Follow-up                 5                 2                 4                 2                 3  
Withdrawal by Subject                 6                 4                 4                 2                 5  
Adverse Event                 4                 3                 7                 4                 8  
Death                 1                 0                 0                 0                 0  
Protocol Violation                 0                 1                 0                 0                 0  
Physician Decision                 1                 1                 0                 0                 0  
Pregnancy                 1                 0                 0                 0                 0  
Unspecified                 14                 15                 7                 4                 9  



  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
Metformin XR Participants received metformin extended release (XR) tablets (in doses titrated over 9 weeks) once daily with the evening meal, plus one placebo capsule before the morning meal and one placebo capsule with the evening meal (to match the canagliflozin capsules administered in other treatment arms) for 26 weeks.
Canagliflozin 100 Milligram (mg) Participants received one 100 milligram (mg) canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks.
Canagliflozin 300 mg Participants received one 300 mg canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks.
Canagliflozin 100 mg + Metformin XR Participants received one 100 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.
Canagliflozin 300 mg + Metformin XR Participants received one 300 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.
Total Total of all reporting groups

Baseline Measures
    Metformin XR     Canagliflozin 100 Milligram (mg)     Canagliflozin 300 mg     Canagliflozin 100 mg + Metformin XR     Canagliflozin 300 mg + Metformin XR     Total  
Number of Participants  
[units: participants]
  237     237     238     237     237     1186  
Age  
[units: years]
Mean (Standard Deviation)
  55.2  (9.75)     54.0  (10.70)     55.8  (9.56)     54.2  (9.58)     55.4  (9.84)     54.9  (9.91)  
Gender  
[units: participants]
           
Female     121     132     113     129     122     617  
Male     116     105     125     108     115     569  
Region of Enrollment  
[units: participants]
           
Argentina     12     19     21     17     20     89  
Brazil     1     2     1     0     0     4  
Czech Republic     8     6     6     6     8     34  
Hungary     2     5     8     9     4     28  
Mexico     33     31     19     38     38     159  
Romania     24     16     21     27     14     102  
Russian Federation     38     38     45     44     37     202  
Slovakia     17     12     22     9     9     69  
South Africa     5     5     4     5     3     22  
South Korea     4     2     2     1     3     12  
Ukraine     50     56     42     40     54     242  
United States     43     45     47     41     47     223  



  Outcome Measures
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1.  Primary:   Change in Glycated Hemoglobin (HbA1c) From Baseline at Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

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

3.  Secondary:   Percentage of Participants With Glycated Hemoglobin (HbAIc) Less Than 7 Percent at Week 26   [ Time Frame: Week 26 ]

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

5.  Secondary:   Percent Change in Fasting High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

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

7.  Secondary:   Number of Participants With Treatment Emergent Adverse Events (AEs)   [ Time Frame: Up to 30 weeks of last study drug administration ]


  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 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: Senior Director Clinical Research
Organization: Janssen Research & Development, LLC
e-mail: ClinicalTrialDisclosure@its.jnj.com


No publications provided


Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01809327     History of Changes
Other Study ID Numbers: CR100034
28431754DIA3011 ( Other Identifier: Janssen Research & Development, LLC )
2011-000400-17 ( EudraCT Number )
Study First Received: March 8, 2013
Results First Received: December 1, 2015
Last Updated: December 1, 2015
Health Authority: United States: Food and Drug Administration
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Ukraine: State Pharmacological Center - Ministry of Health
United States: Federal Government