To Evaluate the Response to Glucagon During Hypoglycemia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the response to Glucagon versus the spontaneous hormonal response to low blood sugar levels in T2DM Patients treated with AZD1656 and Metformin

Official Title
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A Randomised, Open, Two-Way Cross-Over, Phase I Study to Evaluate the Response to Glucagon Versus the Spontaneous Counter-Regulatory Response in T2DM Patients Treated With AZD1656 and Metformin During Hypoglycemia

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: AZD1656
* Drug: Glucagon


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: AZD1656<br>* 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<br>Drug: Glucagon<br>* 1 mg injected 3 hr post AZD1656 morning dose on day 5 alt. day 8<br>|
| Experimental: 2<br> | Drug: AZD1656<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| P-Glucose levels |  | Repeated sampling during the 24 hour period on day 5 and 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type II Diabetes, Counter-regulatory response, Hypoglycemia