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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01020123
First received: November 11, 2009
Last updated: November 22, 2012
Last verified: November 2012
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 Pública 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
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glipizide
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 23, 2014