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

Phase 2

Completed

Conditions: Type II Diabetes

Interventions: Drug: AZD1656
Drug: Placebo

Registration Number: NCT00856908

Lead Sponsor: AstraZeneca

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 Insulin

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	AZD1656	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
2	Placebo	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

Primary Outcome Measures

Name	Time	Method
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	Measured regularly from day before first dose to day after last dose	Number of participants with clinically relevant change of laboratory variables (clinical chemistry, haematology and urinalysis parameters
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

Secondary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD1656	Measured last day of treatment	Dose-adjusted to a total daily dose of 100 mg due to titrated doses
Maximum Plasma Concentration of AZD1656	Measured following the morning dose last day of treatment	Dose-adjusted to a morning dose of 50 mg due to titrated doses
Time to Reach Maximum Plasma Concentration of AZD1656	Measured last day of treatment
P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment	Baseline is the day before first dose, end of treatment is last day 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.
S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment	Baseline is the day before first dose, end of treatment is last day 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
S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment	Baseline is the day before first dose, end of treatment is last day 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.
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