Evaluate Efficacy, Safety and Tolerability of AZD1656 as Add-on Treatment to Metformin in Type 2 Diabetes Mellitus (TD2M) Patients - Full Text View

Purpose

The primary aim is to evaluate Efficacy, Safety and Tolerability of AZD1656 as Add-on Treatment to Metformin in TD2M Patients

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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A 4-month, Randomized, Double-blind, Placebo- and Active-Controlled, Multi-centre, Parallel-Group Study, With an Optional 2-month Extension, to Evaluate Efficacy, Safety and Tolerability of AZD1656 as Add-on Treatment to Metformin in Type 2 Diabetes Mellitus Patients

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2 Potassium

Drug Information available for: Metformin Metformin hydrochloride Glipizide

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

HbA1c: Change From Baseline to 4 Month [ Time Frame: Baseline to 4th Month ] [ Designated as safety issue: No ]
AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue

Secondary Outcome Measures:

FPG: to Evaluate Change From Baseline to 4 Month, Compared With Placebo, FAS Prior to Rescue. [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue.
SMPG: Change From Baseline to 4 Month, Compared With Placebo, FAS Prior to Rescue. [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue.
OGTT/Plasma Glucose [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
The relative change in AUC
OGTT/Insulin [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
The Relative Change in AUC FAS Prior to Rescue
OGTT/C-peptide [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
The relative change, FAS prior to rescue
OGTT/Pro-insulin/Insulin [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
The relative change, FAS prior to rescue
HbA1c ≤ 7 [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Number of responders ≤ 7, FAS prior to rescue.
HbA1c ≤ 6.5 [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Number of Responders ≤ 6.5, FAS Prior to Rescue
LDL-C: Mean Ratio [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.
HDL-C: Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.
Total Cholesterol: Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.
Triglycerides: Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
C-reactive Protein: Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI
Systolic Blood Pressure, Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
Diastolic Blood Pressure, Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
Pulse, Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
Weight, Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
QTcF; Electorcardiagram Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
Haemoglobin; Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
Leukocytes; Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
Sodium; Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
Potassium; Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
Creatinine; Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
ALT; Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
AST; Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
Alkaline Phosphatase; Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
Bilirubin; Change From Baseline [ Time Frame: baseline to 4 month ] [ Designated as safety issue: No ]
Summary statistic of change from baseline
CL/F to Characterise the PK Properties of AZD1656. [ Time Frame: at 4 month ] [ Designated as safety issue: No ]
The value is calculated using an allometric model (of a patient weighting 75 kg). The value is independent treatment given.
EC50 to Characterise the PD Properties of AZD1656. [ Time Frame: at 4 month ] [ Designated as safety issue: No ]
The value is model based. The value is independent treatment given.

Enrollment:	530
Study Start Date:	October 2009
Study Completion Date:	February 2011
Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 AZD1656	Drug: AZD1656 Different doses of AZD1656 administered to 5 groups of patients
Experimental: 2 AZD1656	Drug: AZD1656 Different doses of AZD1656 administered to 5 groups of patients
Experimental: 3 AZD1656	Drug: AZD1656 Different doses of AZD1656 administered to 5 groups of patients
Experimental: 4 AZD1656	Drug: AZD1656 Different doses of AZD1656 administered to 5 groups of patients
Experimental: 5 AZD1656	Drug: AZD1656 Different doses of AZD1656 administered to 5 groups of patients
Placebo Comparator: 6	Drug: Placebo AZD1656 placebo and glipizide placebo administered to 1 group of patients
Active Comparator: 7 Glipizide administered to 1 group of patients	Drug: Glipizide Glipizide administered to 1 group of patients

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

female of non-childbearing potential
Treated with maximally tolerated dose of metformin (≥ 1500mg/day) for at least 10 weeks prior to enrolment.
Patients with HbA1c ≥ 7.5 but ≤ 10% at enrolment visit (Visit 1) can enter cohort 1.Patients with HbA1c between >10 % and <12 % can enter the open-label arm with AZD1656 (cohort 2)

Exclusion Criteria:

Significant cardiovascular event within the last 6 months prior to enrolment or heart failure New York Heart Association (NYHA) class III-IV.
Impaired renal function in terms of GFR<60 ml/min, based on Modification of Diet in Renal Disease Study Group (MDRD) calculation.
Use of warfarin or amiodarone within 3 months prior to enrolment (screening) and use of potent CYP450 inhibitors, eg, ketoconazole and/or macrolide antibiotics within 14 days before randomisation.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01020123

Show 76 Study Locations

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:	Eva Johnsson	AstraZeneca R&D Mölndal
Principal Investigator:	John Wilding, DM FRCP	University Hospital Aintree

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01020123 History of Changes
Other Study ID Numbers:	D1020C00009
Study First Received:	November 11, 2009
Results First Received:	July 24, 2012
Last Updated:	November 22, 2012
Health Authority:	Chile: Instituto de Salud Publica de Chile Germany: Federal Institute for Drugs and Medical Devices Hungary: National Institute of Pharmacy Latvia: State Agency of Medicines Lithuania: State Medicine Control Agency - Ministry of Health Mexico: Federal Commission for Protection Against Health Risks Peru: General Directorate of Pharmaceuticals, Devices, and Drugs Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Romania: National Medicines Agency Sweden: Medical Products Agency United Kingdom: Medicines and Healthcare Products Regulatory Agency United States: Food and Drug Administration

Keywords provided by AstraZeneca:

Type II Diabetes Mellitus
metformin
glipizide

Additional relevant MeSH terms:

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

Glipizide
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013