A Study to Evaluate the Food Effect on Drug Availability, Pharmacokinetic (PK) Properties, Safety and Tolerability of Two Different Dose Combination Therapy of Saxagliptin/Dapagliflozin/Metformin Extended-release (XR) Against Individual Component Co-administration.
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1

Summary: 
      A Study to Assess the Fed-state Bioequivalence of a Triple Fixed-Combination Drug Product
      (FCDP) of 2.5 mg Saxagliptin / 5 mg Dapagliflozin / 1000 mg Metformin XR and 5 mg Saxagliptin
      /10 mg Dapagliflozin /1000 mg Metformin XR Relative to Individual Components (Onglyza and
      XIGDUO XR) Co-administration. A randomized, open-label, cross over design has been chosen to
      minimize the effects of between-subject variability and any period effects on the overall
      results.
    

Detailed description: 
      This study will be randomized, 3-period, 3-treatment, single-dose, open-label, single-center,
      crossover to assess the fed-state bioequivalence of a two triple Fixed-combination Drug
      Product (FCDP) of saxagliptin/dapagliflozin/metformin extended-release (XR) relative to
      individual components co-administered in approximately 84 healthy adult subjects. Eligible
      subjects will be healthy male and female aged 18 to 55 years, with a body weight of 50 to 100
      kg and body mass index (BMI) of 18 to 32 kg/m2. Of the 84 randomized subjects (2 cohorts of
      42 subjects each [3 treatments in each cohort]), at least 72 subjects (36 in each cohort)
      should be evaluable. Each randomized 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 to 6 treatment sequences prescribing the ordered
      sequence of 3 administered treatments with 7 subjects in each treatment sequence. The
      investigational medicinal product (IMPs) will be administered orally at single-dose to
      subjects within 5 minutes after standard meal (light-fat, low-calorie) in the morning (fed
      condition) or following a 10 hour fast (fasted condition). In both cohorts, test product will
      be compared with treatments of fed and fasted conditions Subjects in Cohort 1 will be
      randomized to one of the treatment sequences (ABC), (ACB), (BAC), (BCA), (CAB) or (CBA).

      Treatment A (Reference Product under fed conditions) - Single-dose of 2.5 mg saxagliptin
      (ONGLYZA) and 5 mg dapagliflozin / 1000 mg metformin XR (XIGDUO XR) tablets.

      Treatment B (Test Product under fed conditions) - Single-dose of triple FCDP consisting of
      2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR.

      Treatment C (Test Product fasted conditions) - Single-dose of triple FCDP tablet consisting
      of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR.

      Subjects in Cohort 2 will be randomized to one of the treatment sequences (DEF), (DFE),
      (EDF), (EFD), (FDE) or (FED).

      Treatment D (Reference product under fed conditions) - Single-dose of 5 mg saxagliptin
      (ONGLYZA) and 10 mg dapagliflozin / 1000 mg metformin XR (XIGDUO XR) tablet.

      Treatment E (Test Product under fed conditions) - Single-dose of triple FCDP consisting of 5
      mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR.

      Treatment F (Test Product under fasted conditions) - Single-dose of triple FCDP consisting of
      5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR.

      The study will comprise:

        -  A screening period of maximum 28 days;

        -  Three resident treatment periods - Day before dosing with the IMP (Day -1) until at
           least 72 hours after dosing; and will be discharged on the morning of Day 4; and

        -  A follow-up visit within 5 to 7 days after the last dose of IMP. Treatment periods will
           be separated by a minimum washout period of 7 to 14 days between each IMP dose. The
           duration of the study will be approximately 7 to 9 weeks.
    

Intervention name(s): 2.5 mg Saxagliptin tablet; 5 mg dapagliflozin / 1000 mg metformin XR tablet; Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR; 5 mg saxagliptin; 10 mg dapagliflozin / 1000 mg metformin XR tablet; Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): A competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with Type 2 diabetes mellitus (T2DM).; Dapagliflozin - An inhibitor of sodium-glucose co-transporter 2 (SGLT-2), reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.
Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization.; Saxagliptin - A competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with T2DM.
Dapagliflozin - An inhibitor of SGLT-2, reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.
Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization.; A competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with T2DM.; Dapagliflozin - An inhibitor of SGLT-2, reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.
Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization.; Saxagliptin - A competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with T2DM.
Dapagliflozin - An inhibitor of SGLT-2, reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.
Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Other intervention name(s): 2.5 mg ONGLYZA; 5 / 1000 mg XIGDUO XR; 5 mg ONGLYZA; 10/1000 mg XIGDUO XR
Intervention MeSH terms: Metformin; Dapagliflozin; Saxagliptin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Anti-diabetic; Anti-hyperglycemic agents; Bioequivalence; Fixed-Combination Drug Product (FCDP) of saxagliptin / dapagliflozin / metformin extended-release (XR).; Fed-state bioequivalence (BE); XIGDUO® XR; ONGLYZA®