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

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

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

Study Overview

• Status: Completed
• Conditions: Type II Diabetes Mellitus
• Intervention / Treatment: Drug: AZD1656; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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.

Collaborators and Investigators

• Sponsor: 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

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: October 14, 2009
• First Submitted That Met QC Criteria: October 14, 2009
• First Posted (Estimate): October 15, 2009

Study Record Updates

• Last Update Posted (Estimate): February 26, 2010
• Last Update Submitted That Met QC Criteria: February 25, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: metformin; Type II diabetes mellitus; sulfonylurea
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: D1020C00026