Study to Assess the Safety and Tolerability After Multiple Oral Doses of AZD1656 in Patients With Type 2 Diabetes Mellitus Treated With Metformin

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the 1 month safety and tolerability after multiple oral doses of AZD1656 in patients with Type 2 Diabetes Mellitus Treated with Metformin

Official Title
-----------------
A Randomised, Single-Blind, Placebo-Controlled, Phase IIA Study to Assess the Safety and Tolerability After Multiple Oral Doses of AZD1656 in Patients With Type 2 Diabetes Mellitus Treated With Metformin

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Drug: AZD1656
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or women of non-childbearing potential (postmenopausal, and/or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy/ tubal ligation) Ongoing treatment with metformin on a stable dose of ≥ 1500 mg/day for at least 8 weeks prior to randomisation HbA1c ≤ 10% at enrolment (HbA1c value according to international Diabetes Control and Complications Trial [DCCT] standard) Exclusion Criteria: History of ischemic heart disease, symptomatic heart failure, stroke, transitory ischemic attack or symptomatic peripheral vascular disease Clinically significant abnormalities in ECG, clinical chemistry, haematology, or urine analysis results. Positive test for Hepatitis B surface antigen or antibodies to human immunodeficiency virus (HIV) or antibodies to Hepatitis C virus

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD1656<br>Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days | Drug: AZD1656<br>* Subjects will be treated with tolerable dose twice daily for another 24 days.<br>|
| Placebo Comparator: Placebo<br>Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days | Drug: Placebo<br>* Subjects will be treated with tolerable dose twice daily for another 24 days.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic Blood Pressure, Change From Baseline to End of Treatment |  | Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period | 
| Diastolic Blood Pressure, Change From Baseline to End of Treatment |  | Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period | 
| Pulse, Change From Baseline to End of Treatment |  | Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period | 
| Weight, Change From Baseline to End of Treatment |  | Baseline is the day before first dose, end of treatment is last day of treatment | 
| Clinically Relevant Change of Laboratory Variables | Number of participants with clinically relevant change of laboratory variables (clinical chemistry, haematology and urinalysis parameters | Measured regularly from day before first dose to day after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD1656 | Dose-adjusted to a total daily dose of 100 mg due to titrated doses | Measured last day of treatment | 
| Maximum Plasma Concentration of AZD1656 | Dose-adjusted to a morning dose of 50 mg due to titrated doses | Measured last day of treatment | 
| Time to Reach Maximum Plasma Concentration of AZD1656 |  | Measured last day of treatment | 
| Terminal Elimination Half-life of AZD1656 |  | Measured following the afternoon dose last day of treatment | 
| Apparent Oral Clearance of AZD1656 |  | Measured last day of treatment | 
| P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment | Log ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect and log(Baseline) as covariate. Resulting estimates have been back-transformed from the log-scale and then multiplied by 100 to obtain the relative ratio (end of treatment/placebo) in percent. | Baseline is the day before first dose, end of treatment is last day of treatment | 
| S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment | Log ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect and log(Baseline) as covariate. Resulting estimates have been back-transformed from the log-scale and then multiplied by 100 to obtain the relative ratio (end of treatment/placebo) in percent. | Baseline is the day before first dose, end of treatment is last day of treatment | 
| S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment | Log ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect and log(Baseline) as covariate. Resulting estimates have been back-transformed from the log-scale and then multiplied by 100 to obtain the relative ratio (end of treatment/placebo) in percent. | Baseline is the day before first dose, end of treatment is last day of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type II Diabetes