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
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 April 15, 2014