Safety and Tolerability After Four Weeks of Treatment With AZD1656 in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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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 Insulin

Official Title
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A Randomised, Single-Blind, Placebo-Controlled, Phase IIa Study to Assess the Safety and Tolerability After Multiple Oral Doses of AZD1656 During Four Weeks in T2DM Subjects Treated With Insulin

Conditions
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Type II Diabetes

Intervention / Treatment
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* Drug: AZD1656
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type II diabetes patients, female with non child-bearing potential Subjects with T2DM diagnosis for at least one year, treated with insulin alone or insulin in combination with other anti-diabetic drugs. Subjects must have been treated with insulin the last 3 months prior to enrolment (screening) HbA1c <11% at enrolment (screening) (HbA1c value according to international Diabetes Control and Complications Trial [DCCT] standard). FPG in the range of 7.0 to 13.0 mmol/L (126 to 234 mg/dL) Exclusion Criteria: History of ischemic heart disease, symptomatic heart failure, stroke, transitory ischemic attack or symptomatic peripheral vascular disease Use of glitazones, warfarin, amiodarone within 3 months prior to enrolment (screening) and use of potent CYP450 inhibitors, eg, ketoconazole and macrolide antibiotics within 14 days before randomisation. Any clinically significant abnormality identified on physical examination, laboratory tests or ECG, which in the judgment of the investigator would compromise the patients' safety or successful participation in the clinical study.

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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<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>* Tolerable dose given twice daily<br>|
| Placebo Comparator: 2<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>* Tolerable dose given twice daily<br>|

What is the study measuring?
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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 following the morning dose 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 evening 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 an ANCOVA model, using treatment as fixed factor 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. Changes in percent have been obtained by subtraction by 100. | 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 an ANCOVA model, using treatment as fixed factor 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. Changes in percent have been obtained by subtraction by 100 | 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 an ANCOVA model, using treatment as fixed factor 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. Changes in percent have been obtained by subtraction by 100. | Baseline is the day before first dose, end of treatment is last day of treatment | 

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