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

Phase 2

Completed

• Conditions: Type II Diabetes Mellitus
• Interventions: Drug: AZD1656; Drug: Placebo; Drug: Glipizide

• Registration Number: NCT01020123
• Lead Sponsor: AstraZeneca

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2009-10
• Study First Submitted: 2009-11-11
• Study First Submitted QC: 2009-11-24
• Study First Posted: 2009-11-25
• Primary Completion: 2011-02
• Study Completion: 2011-02
• Results First Submitted: 2012-07-24
• Status Verified: 2012-11
• Results First Submitted QC: 2012-11-22
• Last Update Submitted: 2012-11-22
• Results First Posted: 2012-11-26
• Last Update Posted: 2012-11-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 530

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
3	AZD1656	AZD1656
6	Placebo	-
7	Glipizide	Glipizide administered to 1 group of patients
4	AZD1656	AZD1656
5	AZD1656	AZD1656
1	AZD1656	AZD1656
2	AZD1656	AZD1656

Primary Outcome Measures

Name	Time	Method
HbA1c: Change From Baseline to 4 Month	Baseline to 4th Month	AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue

Secondary Outcome Measures

Name	Time	Method
FPG: to Evaluate Change From Baseline to 4 Month, Compared With Placebo, FAS Prior to Rescue.	baseline to 4 month	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.	baseline to 4 month	AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue.
OGTT/Plasma Glucose	baseline to 4 month	The relative change in AUC
OGTT/Insulin	baseline to 4 month	The Relative Change in AUC FAS Prior to Rescue
OGTT/C-peptide	baseline to 4 month	The relative change, FAS prior to rescue
OGTT/Pro-insulin/Insulin	baseline to 4 month	The relative change, FAS prior to rescue
HbA1c ≤ 7	baseline to 4 month	Number of responders ≤ 7, FAS prior to rescue.
HbA1c ≤ 6.5	baseline to 4 month	Number of Responders ≤ 6.5, FAS Prior to Rescue
LDL-C: Mean Ratio	baseline to 4 month	Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.
HDL-C: Change From Baseline	baseline to 4 month	Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.
Total Cholesterol: Change From Baseline	baseline to 4 month	Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.
Triglycerides: Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
C-reactive Protein: Change From Baseline	baseline to 4 month	Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI
Systolic Blood Pressure, Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
Diastolic Blood Pressure, Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
Pulse, Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
Weight, Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
QTcF; Electorcardiagram Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
Haemoglobin; Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
Leukocytes; Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
Sodium; Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
Potassium; Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
Creatinine; Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
ALT; Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
AST; Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
Alkaline Phosphatase; Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
Bilirubin; Change From Baseline	baseline to 4 month	Summary statistic of change from baseline
CL/F to Characterise the PK Properties of AZD1656.	at 4 month	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.	at 4 month	The value is model based. The value is independent treatment given.

Trial Locations

Locations (1)

Research Site; 🇬🇧 West Lothian, United Kingdom