Trial Outcomes & Findings for An Efficacy, Safety, and Tolerability Study of Canagliflozin in the Treatment of Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy (NCT NCT01340664)

Last Updated: 2014-09-16

Results Overview

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

279 participants

Primary outcome timeframe

Day 1 (Baseline) and Week 18

Results posted on

2014-09-16

Participant Flow

This study evaluated the efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus with inadequate control despite treatment with metformin. The study was conducted between 27 June 2011 and 20 April 2012 and recruited patients from 60 study centers located in 7 countries worldwide.

A total of 279 patients were randomly allocated to the 3 treatment arms in the study. All 279 patients received at least 1 dose of study drug and were included in the modified intent-to-treat analysis set which was used for the efficacy and safety analyses.

Participant milestones

Participant milestones
Measure	Placebo Each patient received matching placebo twice daily for 18 weeks.	Canagliflozin 50 mg Bid Each patient received 50 mg canagliflozin twice daily for 18 weeks.	Canagliflozin 150 mg Bid Each patient received 150 mg canagliflozin twice daily for 18 weeks.
Overall Study STARTED	93	93	93
Overall Study COMPLETED	86	85	80
Overall Study NOT COMPLETED	7	8	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Each patient received matching placebo twice daily for 18 weeks.	Canagliflozin 50 mg Bid Each patient received 50 mg canagliflozin twice daily for 18 weeks.	Canagliflozin 150 mg Bid Each patient received 150 mg canagliflozin twice daily for 18 weeks.
Overall Study Adverse Event	0	1	7
Overall Study Lost to Follow-up	2	0	2
Overall Study Withdrawal by Subject	2	4	0
Overall Study Glycemic withdrawal criteria	2	0	0
Overall Study Creatinine or eGFR withdrawal criteria	0	1	2
Overall Study Other	1	2	2

Baseline Characteristics

An Efficacy, Safety, and Tolerability Study of Canagliflozin in the Treatment of Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=93 Participants Each patient received matching placebo twice daily for 18 weeks.	Canagliflozin 50 mg Bid n=93 Participants Each patient received 50 mg canagliflozin twice daily for 18 weeks.	Canagliflozin 150 mg Bid n=93 Participants Each patient received 150 mg canagliflozin twice daily for 18 weeks.	Total n=279 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	79 Participants n=5 Participants	69 Participants n=7 Participants	75 Participants n=5 Participants	223 Participants n=4 Participants
Age, Categorical >=65 years	14 Participants n=5 Participants	24 Participants n=7 Participants	18 Participants n=5 Participants	56 Participants n=4 Participants
Age, Continuous	57 years STANDARD_DEVIATION 9.32 • n=5 Participants	58.6 years STANDARD_DEVIATION 8.88 • n=7 Participants	56.7 years STANDARD_DEVIATION 10.33 • n=5 Participants	57.4 years STANDARD_DEVIATION 9.53 • n=4 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	53 Participants n=7 Participants	49 Participants n=5 Participants	149 Participants n=4 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	40 Participants n=7 Participants	44 Participants n=5 Participants	130 Participants n=4 Participants
Region Enroll CANADA	17 participants n=5 Participants	11 participants n=7 Participants	12 participants n=5 Participants	40 participants n=4 Participants
Region Enroll CZECH REPUBLIC	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants	12 participants n=4 Participants
Region Enroll MEXICO	10 participants n=5 Participants	12 participants n=7 Participants	10 participants n=5 Participants	32 participants n=4 Participants
Region Enroll ROMANIA	13 participants n=5 Participants	15 participants n=7 Participants	9 participants n=5 Participants	37 participants n=4 Participants
Region Enroll RUSSIAN FEDERATION	18 participants n=5 Participants	17 participants n=7 Participants	20 participants n=5 Participants	55 participants n=4 Participants
Region Enroll SLOVAKIA	10 participants n=5 Participants	9 participants n=7 Participants	11 participants n=5 Participants	30 participants n=4 Participants
Region Enroll UNITED STATES	23 participants n=5 Participants	25 participants n=7 Participants	25 participants n=5 Participants	73 participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 (Baseline) and Week 18

Population: This analysis used the modified intent-to-treat analysis set (all patients who were randomly assigned to a treatment group and received at least 1 dose of study drug). The last-observation-carried-forward method was applied when Week 18 values were missing. The table includes only patients with both baseline and post baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Each patient received matching placebo twice daily for 18 weeks.	Canagliflozin 50 mg Bid n=90 Participants Each patient received 50 mg canagliflozin twice daily for 18 weeks	Canagliflozin 150 mg Bid n=91 Participants Each patient received 150 mg canagliflozin twice daily for 18 weeks
Change in HbA1c From Baseline to Week 18	-0.01 Percent Standard Error 0.069	-0.45 Percent Standard Error 0.070	-0.61 Percent Standard Error 0.069

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 18

The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Each patient received matching placebo twice daily for 18 weeks.	Canagliflozin 50 mg Bid n=90 Participants Each patient received 50 mg canagliflozin twice daily for 18 weeks	Canagliflozin 150 mg Bid n=91 Participants Each patient received 150 mg canagliflozin twice daily for 18 weeks
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18	8.1 mg/dL Standard Error 3.291	-15.5 mg/dL Standard Error 3.327	-15.9 mg/dL Standard Error 3.313

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 18

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Each patient received matching placebo twice daily for 18 weeks.	Canagliflozin 50 mg Bid n=90 Participants Each patient received 50 mg canagliflozin twice daily for 18 weeks	Canagliflozin 150 mg Bid n=91 Participants Each patient received 150 mg canagliflozin twice daily for 18 weeks
Percent Change in Body Weight From Baseline to Week 18	-0.6 Percent change Standard Error 0.3	-2.8 Percent change Standard Error 0.3	-3.2 Percent change Standard Error 0.3

SECONDARY outcome

Timeframe: Week 18

The table below shows the percentage of patients with HbA1c \<7% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Each patient received matching placebo twice daily for 18 weeks.	Canagliflozin 50 mg Bid n=90 Participants Each patient received 50 mg canagliflozin twice daily for 18 weeks	Canagliflozin 150 mg Bid n=91 Participants Each patient received 150 mg canagliflozin twice daily for 18 weeks
Percentage of Patients With HbA1c <7% at Week 18	31.5 Percentage of Participants	47.8 Percentage of Participants	57.1 Percentage of Participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Canagliflozin 50 mg Bid

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Canagliflozin 150 mg Bid

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=93 participants at risk Each patient received matching placebo twice daily for 18 weeks	Canagliflozin 50 mg Bid n=93 participants at risk Each patient received 50 mg canagliflozin twice daily for 18 weeks.	Canagliflozin 150 mg Bid n=93 participants at risk Each patient received 150 mg canagliflozin twice daily for 18 weeks
Gastrointestinal disorders Oroantral fistula	0.00% 0/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.	0.00% 0/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.	1.1% 1/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.
Infections and infestations Pyelonephritis	0.00% 0/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.	0.00% 0/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.	1.1% 1/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.
Injury, poisoning and procedural complications Postoperative wound complication	0.00% 0/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.	0.00% 0/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.	1.1% 1/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.	0.00% 0/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.	1.1% 1/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.
Renal and urinary disorders Nephrolithiasis	0.00% 0/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.	0.00% 0/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.	1.1% 1/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.
Reproductive system and breast disorders Dysfunctional uterine bleeding	1.1% 1/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.	0.00% 0/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.	0.00% 0/93 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks. Only patients who had at least one of the treatment-emergent adverse events listed in the "Other (non-Serious) Adverse Event" table are included in the total number of patients with non-serious adverse Events.

Other adverse events

Adverse event data not reported

Additional Information

Vice President, Franchise Medical Leader, Cardiovascular & Metabolism Franchise

Janssen Research & Development, LLC

Phone: 1 908 927-5775

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. Expedited reviews will be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
Publication restrictions are in place

Restriction type: OTHER