Treatment Differences Between Canagliflozin and Placebo in Insulin Secretion in Subjects With Type 2 Diabetes Mellitus (T2DM)
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to assess changes from baseline in insulin sensitivity, hepatic
      fat content and beta cell function after approximately 24-25 weeks of treatment with
      canagliflozin compared to placebo in participants with type 2 diabetes mellitus (T2DM) with
      inadequate glycemic (blood sugar) control on metformin monotherapy or on combination therapy
      with metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor.
    

Detailed description: 
      This is a double-blind (neither physician nor participants knows the treatment that the
      participant receives), randomized (the study medication is assigned by chance),
      placebo-controlled (an inactive substance is compared with a medication to test whether the
      medication has a real effect in a clinical study), parallel-groups study which will be
      conducted at 2 clinical research centers (CRC) in the US. Approximately 56 participants, ages
      25-70 years, with T2DM inadequately controlled on either metformin monotherapy or combination
      therapy with metformin and a DPP-4 inhibitor, will be enrolled. The study has 3 phases:
      pre-treatment, double-blind treatment, and post-treatment.

      Pre-Treatment Phase will consist of a screening visit (Week -5), 14 days Single- Blind
      Placebo Run-in period, followed by 14 days of Single-Blind Placebo Baseline Period, during
      which participants will be randomized (1:1) to one of 2 treatment groups, either
      canagliflozin or placebo. Double-Blind Treatment Phase begins on Day 1, and ends at
      approximately Week 25, during which participants will be assessed at least biweekly at
      outpatient visits or by telephone contact. Canagliflozin treatment will be initiated at 100
      mg/day, with up-titration to 300 mg/day, consistent with the approved INVOKANA® US
      Prescribing Information 2013. During post-treatment phase, a follow-up visit will occur
      within approximately 28 days after the last dose of study drug.

      At baseline and after 24 weeks of treatment with canagliflozin, hepatic and peripheral
      insulin sensitivity will be assessed using tracer labeled euglycemic clamp technique; hepatic
      fat content will be determined using 1H nuclear magnetic resonance spectroscopy (MRS); beta
      cell function (insulin secretion rate and beta cell glucose sensitivity) will be assessed
      during mixed meal tolerance test (MMTT); substrate oxidation and energy production rates will
      be measured using indirect calorimetry during euglycemic clamp and MMTT.

      During the study, participants will remain on their stable dose regimens of metformin or
      combination metformin DPP-4 inhibitor therapy, unless the investigator considers dose
      modification to be medically necessary. The total study duration for each participant
      participating in this study will be up to approximately 34 weeks.
    

Intervention name(s): Canagliflozin, 100 mg; Canagliflozin, 300 mg; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): One 100 mg capsule taken orally (by mouth) once daily; One 300 mg capsule taken orally (by mouth) once daily; One placebo capsule (inactive medication) once daily.
Intervention MeSH terms: Canagliflozin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Diabetes Mellitus, Type 2; Metformin; Canagliflozin; INVOKANA®; Insulin sensitivity; DPP-4 inhibitor; dipeptidyl peptidase-4