Safety and Tolerability of AZD1656 in Type 2 Diabetes Mellitus (T2DM) Patients Treated With Metformin and Sulfonylurea

Study Overview
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Brief Summary
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The primary aim of this study is to evaluate the safety and tolerability of AZD1656 in T2DM patients treated with metformin and sulfonylurea.

Official Title
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A Randomized, Single-blind, Placebo-controlled, Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD1656 Compared to Placebo in T2DM Patients Treated With Metformin and Sulfonylurea

Conditions
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Type II Diabetes Mellitus

Intervention / Treatment
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* Drug: AZD1656
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or females of non-childbearing potential Patients treated with a combination of Metformin and SU (glyburide, glimepiride, glibenclamide, glipizide or gliclazide) in stable doses for at least 2 months prior to enrolment visit Patients should have FPG in the range of 6,0 to 14 mmol/L (108 to 250 mg/dL) at enrolment and on the morning of randomisation Exclusion Criteria: History of ischemic heart disease, symptomatic heart failure, stroke, transitory ischemic attack or symptomatic peripheral vascular disease Impaired renal function in terms of GFR<60 ml/min Use of insulin, glitazones, gemfibrozil, warfarin, amiodarone within 3 months prior to enrolment (screening) and use of potent CYP450 inhibitors, e.g., ketoconazole within 14 days before randomisation

Ages Eligible for Study
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Minimum Age: 30 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: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD1656<br> | Drug: AZD1656<br>* Dose titration of oral suspension of AZD165 during 3 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 6 days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Dose titration of oral suspension of placebo during 3 days given twice daily. Subjects will thereafter be for another 6 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety variables (AE, BP, pulse, plasma glucose, laboratory variables, weight and ECG |  | AE will be collected from the time for randomisation until follow-up visit. Safety variables and vital signs will be measured at the pre-entry, during study days -2 to 10 and at the follow-up visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic variables: (Area under the plasma concentration vs. time curve (AUC), maximum plasma concentration (Cmax), time to reach maximum plasma concentration (tmax), terminal elimination half-life (t½) and apparent oral clearance (CL/F) |  | Blood samples for analysis of plasma concentrations of AZD1656 will be collected on study days 6 and 9. The samples for analysis of glipizide will be collected on study days -1 and 6. | 
| Pharmacodynamic variables: 24 h plasma glucose, Insulin |  | Samples for 24-hour plasma glucose and insulin will be collected on study days -1, 6 and 9. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type II diabetes mellitus, metformin, sulfonylurea