To Evaluate the Response to Glucagon During Hypoglycemia

• AZD1656 (Drug): Dose titration of oral suspension during 2 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose for another 6 days. On day 5 and 8 the dose will be given as a single dose
• Glucagon (Drug): 1 mg injected 3 hr post AZD1656 morning dose on day 5 alt. day 8

Primary outcomes

• P-Glucose levels [Repeated sampling during the 24 hour period on day 5 and 8]

Secondary outcomes

• Safety and tolerability (AE, BP, pulse, plasma glucose, laboratory variables, weight and ECG) [Frequent measurements during the study period]
• Pharmacokinetic variables (Area under the plasma conc-time curve from time 0 to 24 hours post dose (AUC0-24), maximum plasma conc(Cmax), time to reach maximum plasma conc(tmax), terminal elimination half-life and apparent oral clearance [Repeated sampling during the 24 hour period on day 5 and 8]
• Pharmacodynamics (P-Glucose, S-Insulin and S-C-peptide) [Repeated sampling during the 24 hour period on day 5 and 8]

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* type II diabetes patients, female with non child-bearing potential
* T2DM diagnosis confirmed by C-peptide >0.3nmol/L and no glutamic acid decarboxylate (GAD) antibodies at enrolment (screening)
* Treatment with metformin alone with a total daily dose not less than 1 000 mg. Stable glycaemic control indicated by unchanged treatment within 3 months prior to enrolment

Exclusion Criteria:

* History of ischemic heart disease, symptomatic heart failure, stroke, transitory ischemic attack or symptomatic peripheral vascular disease
* Signs of diabetic proliferative retinopathy or diabetic maculopathy, at screening or on an ophthalmological examination within 3 months from start of study
* Participating in another clinical study during the last 30 days prior to enrolment

• Klas Malmberg, MD, PhD, Prof., Study director, AstraZeneca R&D Mölndal
• Marcus Hompesch, MD, Principal investigator, Profil Institut for Clinical Research Inc.