A Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics After High Single Ascending Oral Doses of AZD1656 in T2DM Patients

Study Overview
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Brief Summary
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The purpose of this study is to investigate safety and tolerability after high Single Ascending Oral Doses of AZD1656.

Official Title
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A Randomised, Single-Blind, Placebo-Controlled, Single-Centre Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After High Single Ascending Oral Supratherapeutic Doses of AZD1656 in Male Type 2 Diabetes Mellitus (T2DM) Patients

Conditions
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Type 2 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: Provision of signed and dated, written informed consent prior to any study specific procedures. Male, T2DM patients aged 20-60 years Treatment with 1 to 2 OADs as Therapy for T2DM for at least 30 days prior to enrollment Patients should not have been treated with glitazones within 6 months prior to enrollment Male T2DM patients without known cardiovascular disease, with the exception of Grade 1 hypertension without secondary organ involvement (eg. grade 1 HT is allowed if no eye, kidney disease or LVH has been documented). Exclusion Criteria: History of ischemic heart disease , heart failure, stroke, transitory ischemic attack or peripheral vascular disease. Prolonged QTcF>450 msec or shortened QTcF<350 msec or family history of long QT syndrome. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. Systolic BP>159 mmHg or diastolic BP>99 mmHg at screening and on Day-1

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

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: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A - AZD1656<br>AZD1656 | Drug: AZD1656<br>* 3 escalating dose levels are planned. Administration of the escalating doses of AZD1656 will be based on review of available safety from the previous dose.<br>|
| Placebo Comparator: B - Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Objective to assess the safety and tolerability of AZD1656, following oral administration of single ascending supratherapeutic doses of AZD1656 to patients with type 2 diabetes mellitus in a fasted state. |  | From screening until Follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary objective to evaluate the pharmacokinetics (AUC, Cmax, t1/2, CL/F) of AZD1656 and its metabolite following oral administration of single ascending supratherapeutic doses of AZD1656 |  | From pre-dose Day 1 to 48 hours after dose | 
| Secondary objective to evaluate glucose levels and insulin secretion in type 2 diabetes mellitus patients following oral administration of single ascending supratherapeutic doses of AZD1656 |  | Glucose levels from Day -1 to day 3 | 
| Secondary objective to evaluate glucose levels and insulin secretion in type 2 diabetes mellitus patients following oral administration of single ascending supratherapeutic doses of AZD1656 |  | Insuline secretion from Day -1 to 2. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus