Safety and Tolerability After Four Weeks of Treatment With AZD1656 in Patients With Type 2 Diabetes - Full Text View

Purpose

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

Condition	Intervention	Phase
Type II Diabetes	Drug: AZD1656 Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Systolic Blood Pressure, Change From Baseline to End of Treatment [ Time Frame: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period ] [ Designated as safety issue: No ]
Diastolic Blood Pressure, Change From Baseline to End of Treatment [ Time Frame: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period ] [ Designated as safety issue: No ]
Pulse, Change From Baseline to End of Treatment [ Time Frame: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period ] [ Designated as safety issue: No ]
Weight, Change From Baseline to End of Treatment [ Time Frame: Baseline is the day before first dose, end of treatment is last day of treatment ] [ Designated as safety issue: No ]
Clinically Relevant Change of Laboratory Variables [ Time Frame: Measured regularly from day before first dose to day after last dose ] [ Designated as safety issue: No ]
Number of participants with clinically relevant change of laboratory variables (clinical chemistry, haematology and urinalysis parameters

Secondary Outcome Measures:

Area Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD1656 [ Time Frame: Measured last day of treatment ] [ Designated as safety issue: No ]
Dose-adjusted to a total daily dose of 100 mg due to titrated doses
Maximum Plasma Concentration of AZD1656 [ Time Frame: Measured following the morning dose last day of treatment ] [ Designated as safety issue: No ]
Dose-adjusted to a morning dose of 50 mg due to titrated doses
Time to Reach Maximum Plasma Concentration of AZD1656 [ Time Frame: Measured last day of treatment ] [ Designated as safety issue: No ]
Terminal Elimination Half-life of AZD1656 [ Time Frame: Measured following the evening dose last day of treatment ] [ Designated as safety issue: No ]
Apparent Oral Clearance of AZD1656 [ Time Frame: Measured last day of treatment ] [ Designated as safety issue: No ]
P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment [ Time Frame: Baseline is the day before first dose, end of treatment is last day of treatment ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline is the day before first dose, end of treatment is last day of treatment ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline is the day before first dose, end of treatment is last day of treatment ] [ Designated as safety issue: No ]
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.

Enrollment:	20
Study Start Date:	February 2009
Study Completion Date:	August 2009
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Ages Eligible for Study:	30 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00856908

Locations

United States, California
Research Site
Chula Vista, California, United States

Sponsors and Collaborators

AstraZeneca

Investigators

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

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00856908 History of Changes
Other Study ID Numbers:	D1020C00020
Study First Received:	March 5, 2009
Results First Received:	July 24, 2012
Last Updated:	November 27, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:

Type II Diabetes

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on May 23, 2013