Japan Dose Regimen Study of AZD1656 in Japanese Type 2 Diabetes Mellitus Patients

• Evaluate the change of HbA1c [ Time Frame: 4 month visit ] [ Designated as safety issue: No ]
• Evaluate the change of HbA1c [ Time Frame: at 1 month visit ] [ Designated as safety issue: No ]
• Evaluate the change of HbA1c [ Time Frame: 2 month visit ] [ Designated as safety issue: No ]
• Evaluate the change of HbA1c [ Time Frame: 3 month visit ] [ Designated as safety issue: No ]
• Evaluate the change of HbA1c [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]

• Change in Fasting Plasma Glucose (FPG) [ Time Frame: from baseline to 4 months ] [ Designated as safety issue: No ]
• Number of Responders in Terms of HbA1C ≤ 7% [ Time Frame: at 4th month ] [ Designated as safety issue: No ]
• Number of Responders in Terms of HbA1C ≤ 6.5% [ Time Frame: at 4th month ] [ Designated as safety issue: No ]
• Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: from baseline to 4 months ] [ Designated as safety issue: No ]
• Percentage Change in High-density Lipoprotein Cholesterol (HDL-C) [ Time Frame: from baseline to 4 months ] [ Designated as safety issue: No ]
• Percentage Change in Triglycerides [ Time Frame: from baseline to 4 months ] [ Designated as safety issue: No ]
• Change in High-sensitivity C-reactive Protein (Hs-CRP) [ Time Frame: from baseline to 4 months ] [ Designated as safety issue: No ]

• Number of participants with adverse events (AE) as a measure of safety and tolerability of AZD1656 [ Time Frame: AEs will be collected at every visit throughout the study up to 4 months ] [ Designated as safety issue: Yes ]
• Change of fasting plasma glucose (FPG) and number of responders in terms of HbA1C less than 7% and less than 6.5% Time frame: AEs will be collected at every visit throughout the study up to 4 months [ Time Frame: FPG: from baseline to 4 months. HbA1C: number of responders at 4 months ] [ Designated as safety issue: No ]
• Change of total Cholesterol, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HLD), triglycerides, and high-sensitivity C-Reactive protein (hs-CRP) [ Time Frame: From baseline to 4 months ] [ Designated as safety issue: No ]

The purpose of this study is to compare the effect on glucose control of 3 different AZD1656 dosing regimens with placebo in Japanese type 2 diabetes mellitus (T2DM) patients, as evaluated by the change in HbA1c from baseline to the end of treatment at 4 months.

• Drug: AZD1656
  Oral tablet administered twice daily during 4 months
• Drug: Placebo
  administered twice daily during 4 months

• Experimental: high
  AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)
  Intervention: Drug: AZD1656
• Experimental: Middle
  AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)
  Intervention: Drug: AZD1656
• Experimental: low
  AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)
  Intervention: Drug: AZD1656
• Placebo Comparator: 4
  Intervention: Drug: Placebo

Inclusion Criteria:

• women of non-childbearing potential.
• Provision of informed consent prior to any study specific procedures
• Naïve T2DM patients with HbA1c ≥ 7.5% but ≤ 10% or T2DM Patients treated with one or two oral anti-hyperglycaemic agent(s) with HbA1c ≥ 7.5% but ≤ 9.5% at enrolment visit (Visit1)

Exclusion Criteria:

• Clinically relevant medical history or concurrent disease such as cardiovascular disease, renal disease, hepatic disease and haematological disease.
• The investigator(s) judged that the Subject should not participate in the study according to screening test or medical history.
• Participation in another clinical trial and/or intake of another investigational drug within the last 30 days prior to enrolment visit