Study to Assess the Safety and Tolerability After Multiple Oral Doses of AZD1656 in Patients With Type 2 Diabetes Mellitus Treated With Metformin

A Randomised, Single-Blind, Placebo-Controlled, Phase IIA Study to Assess the Safety and Tolerability After Multiple Oral Doses of AZD1656 in Patients With Type 2 Diabetes Mellitus Treated With Metformin

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 Metformin

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: AZD1656; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, 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 women of non-childbearing potential (postmenopausal, and/or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy/ tubal ligation)
• Ongoing treatment with metformin on a stable dose of ≥ 1500 mg/day for at least 8 weeks prior to randomisation
• HbA1c ≤ 10% at enrolment (HbA1c value according to international Diabetes Control and Complications Trial [DCCT] standard)

Exclusion Criteria:

• History of ischemic heart disease, symptomatic heart failure, stroke, transitory ischemic attack or symptomatic peripheral vascular disease
• Clinically significant abnormalities in ECG, clinical chemistry, haematology, or urine analysis results. Positive test for Hepatitis B surface antigen or antibodies to human immunodeficiency virus (HIV) or antibodies to Hepatitis C virus

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: 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	Drug: AZD1656; Subjects will be treated with tolerable dose twice daily for another 24 days.
Placebo Comparator: 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	Drug: Placebo; Subjects will be treated with tolerable dose twice daily for another 24 days.

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
Time to Reach Maximum Plasma Concentration of AZD1656		Measured last day of treatment
Apparent Oral Clearance of AZD1656		Measured last day of treatment
Maximum Plasma Concentration of AZD1656	Dose-adjusted to a morning dose of 50 mg due to titrated doses	Measured last day of treatment
Terminal Elimination Half-life of AZD1656		Measured following the afternoon dose 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 a mixed-effect ANOVA model, using treatment as fixed effect 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.	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 a mixed-effect ANOVA model, using treatment as fixed effect 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.	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 a mixed-effect ANOVA model, using treatment as fixed effect 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.	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: Emanuel P DeNoia, M.D, Healthcare Discoveries LLC Icon Development Solutions

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Estimate): November 16, 2012
• Last Update Submitted That Met QC Criteria: October 16, 2012
• Last Verified: October 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: D1020C00019