Bioequivalence Study of Combination Tablets of Saxagliptin / Dapagliflozin / Metformin XR (Extended-release) and Dapagliflozin / Metformin XR Relative to Individual Components in Healthy Subjects
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1

Summary: 
      In this integrated, Phase I study, the safety, tolerability, food effect, and pharmacokinetic
      (PK) properties of Fixed-Dose Combination Tablets of Saxagliptin / Dapagliflozin / Metformin
      XR and Dapagliflozin / Metformin XR Relative to Individual Components in Healthy Subjects
      will be investigated.
    

Detailed description: 
      This study will be an open-label, randomized, 3-period, 3-treatment, single-dose crossover
      study in healthy subjects (males and females), performed at a single study center, conducted
      in 3 cohorts. A total of 126 healthy male or female subjects (3 cohorts of 42 subjects each
      [each cohort consisting of 3 treatments]) will be randomized in this study to ensure that at
      least 108 subjects (36 in each cohort) are evaluable. Each subject will receive 3 single-dose
      treatments, and each treatment will be administered within 1 of the 3 successive treatment
      periods. Within each cohort, subjects will be randomized to 1 of 6 treatment sequences with 7
      subjects prescribing the ordered sequence of 3 administered treatments in each treatment
      sequence, and will receive the IMPs in either a fasted or fed-state according to the assigned
      treatment. For fed-state cohorts, all doses of study drug will be administered to subjects
      after consuming a standard meal (light fat, low calorie) in the morning. Subjects will start
      consuming the meal 30 minutes prior to the dose and will finish the meal within 25 minutes.
      Dosing will then start after 30 minutes after the start of the meal. Subjects in the fasted
      state cohort will be fasted overnight (at least 10 hours) before dosing

      The study will comprise:

        -  A Screening period of maximum 28 days;

        -  Three treatment periods during which subjects will be resident in the Unit from the day
           before dosing with the IMP (Day -1) until at least 72 hours after dosing; discharged on
           the morning of Day 4; and

        -  A final Follow-up Visit within 5 to 7 days after the last administration of the IMP.

      There will be a minimum washout period of 7 to 14 days between each dose administration
    

Intervention name(s): 2.5 mg saxagliptin / 5 mg dapagliflozin / 850 mg metformin XR FDC tablet; 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR FDC tablet; 5 mg dapagliflozin / 850 mg metformin XR FDC; 5 mg dapagliflozin / 1000 mg metformin XR FDC; 2.5 mg ONGLYZA® (saxagliptin) tablet; 5 mg Forxiga® (dapagliflozin) tablet; 500 mg Glucophage XR®
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Used in Treatment B and Treatment E.; Used in Treatment A and Treatment D.; Used in Treatment H.; Used in Treatment G.; Used in treatments C and F.; Used in treatments C, F and I.; Used in treatments C, F and I.
Intervention MeSH terms: Metformin; Dapagliflozin; Saxagliptin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Type 2 diabetes mellitus, saxagliptin, dapagliflozin, metformin XR, fixed-dose combination, healthy subjects, crossover, cohorts.