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

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT00995787

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

18.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Type II Diabetes Mellitus	Drug: AZD1656 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Feb 1, 2010

Actual Study Completion Date :

Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD1656	Drug: AZD1656 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
Placebo Comparator: Placebo	Drug: Placebo Dose titration of oral suspension of placebo during 3 days given twice daily. Subjects will thereafter be for another 6 days

Arm

Intervention/Treatment

Experimental: AZD1656

Drug: AZD1656

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

Placebo Comparator: Placebo

Drug: Placebo

Dose titration of oral suspension of placebo during 3 days given twice daily. Subjects will thereafter be for another 6 days

Outcome Measures

Primary Outcome Measures

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

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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	San Diego	California	United States

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director: Klas Malmberg, MD, PhD, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden
Principal Investigator: Marcus Dr. Marcus Hompesch, Dr, Profil Institute for Clinical Research Inc.855 3rd Avenue, Suite 4400Chula VistaCA 91911, USA