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

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

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

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, 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:

• 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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 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; Tolerable dose given twice daily
Placebo Comparator: 2; 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; Tolerable dose given twice daily

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 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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Klas Malmberg, MD, PhD, Prof., AstraZeneca R&D Mölndal; Principal Investigator: Marcus Hompesch, MD, Profil Institut for Clinical Research Inc.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: March 5, 2009
• First Submitted That Met QC Criteria: March 5, 2009
• First Posted (Estimate): March 6, 2009

Study Record Updates

• Last Update Posted (Estimate): December 6, 2012
• Last Update Submitted That Met QC Criteria: November 27, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Type II Diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: D1020C00020