A Study of Effects of Canagliflozin as Add-on Therapy to Insulin in the Treatment of Participants With Type 1 Diabetes Mellitus (T1DM)

This is a randomized (the study medication is assigned by chance), double-blind (neither
physician nor participant knows the identity of the assigned treatment), placebo-controlled
(an inactive substance that is compared with a medication to test whether the medication has
a real effect) parallel-group, multicenter study of canagliflozin as an addition to insulin
therapy for participants with type 1 diabetes mellitus and inadequate glycemic control.

Approximately 330 participants will be randomly assigned in a 1:1:1 ratio to either
canagliflozin 100 mg, canagliflozin 300 mg, or placebo groups. About 90 participants (30 per
treatment group) will be selected for a substudy with a purpose of a continuous glucose
monitoring (CGM) assessment for 7 days at baseline and 7 days at the end of treatment.

The total duration of the participation will be about 22 weeks, during which participants
will need to return to investigational sites for approximately 9 visits. During the study
participants will receive advice on treatment of hypoglycemia and diabetic ketoacidosis
(DKA), as well as on compliance with diet and exercise.

Inclusion Criteria:

- Must have type 1 diabetes mellitus (T1DM) for at least 1 year

- Must have have inadequate glycemic control (as defined by glycosylated hemoglobin
level of >= 7.0% to <= 9.0%) on basal plus bolus insulin at screening

- Must have body mass index 21 to 35 kg/m2 inclusive

- Must be on a total daily dose of insulin >= 0.6 IU/kg at screening

- Must be on a stable insulin regimen for at least 8 weeks prior to screening

Exclusion Criteria:

- History of T2DM, pancreas or β-cell transplantation, or diabetes secondary to
pancreatitis or pancreatectomy

- Severe hypoglycemia (defined as an event required assistance from another person, or
which resulted in seizure or loss of consciousness) within 6 months prior to study
start

- Diabetic ketoacidosis within 6 months prior to study start

- History of hereditary glucose-galactose malabsorption or primary renal glycosuria

- An ongoing, inadequately controlled thyroid disorder