Study To Assess the Pharmacokinetics of AZD1656 During Coadministration With Simvastatin

• AZD1656 (Drug): Oral tablet, BID dose
• simvastatin (Drug): Oral tablet, single dose

Primary outcomes

• To evaluate the effect of AZD1656 on the steady state pharmacokinetics of simvastatin (including simvastatin acid) and vice versa by assessment of AUC(0-24) and Cmax. [Frequent blood samples for PK analysis will be drawn during 24 hours post morning dose on day 4 in each treatment period (1-3)]

Secondary outcomes

• To evaluate the effect of AZD1656 on the steady state pharmacokinetics of simvastatin and simvastatin acid and vice versa by assessment of tmax, t1/2 and CL/F (only for AZD1656) [Frequent serial blood samples will be drawn during 24 hours post morning dose on Day 4 in each treatment period (1-3)]
• To evaluate the steady state pharmacokinetics of the AZD1656 metabolite when AZD1656 is administered with and without simvastatin, by assessment of AUC(0-24), Cmax and tmax. [Frequent serial blood samples will be drawn during 24 hours post morning dose on Day 4 in each treatment period (1-3)]
• To evaluate the effect of AZD1656 on the pharmacodynamics of simvastatin by assessment of AUC(0-t) and Cmax of active 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors. [Frequent serial blood samples will be drawn during 24 hours post morning dose on Day 4 in each treatment period (1-3)]
• To evaluate the safety and tolerability of AZD1656 alone and in combination with simvastatin by assessments of adverse events, laboratory variables, electrocardiogram, blood pressure, pulse, results of physical examination, and weight. [At pre entry, during the study days,]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patients with a clinical diagnosis of T2DM for at least 1 year, treated with any metformin or metformin with one other oral anti-diabetic drug (OAD)
* Body mass index between greater than or equal to 19 and less than or equal to 42 kg/m2
* HbA1c greater than 6.5% at enrollment

Exclusion Criteria:

* Clinically significant illness or clinically relevant trauma, as judged by the Investigator, within 2 weeks before the first administration of the IP
* Significant cardiovascular event within the last 6 months prior to enrollment (eg, myocardial infarction/acute coronary syndrome, revascularisation procedure, stroke or transient ischaemic attack) or heart failure New York Heart Association (NYHA) class III-IV

• Jolene K. Berg, MD, Principal investigator, Cetero Research, Inc.
• Stanko Skrtic, Study director, AstraZeneca
• Mirjana Kujacic, Study chair, AstraZeneca