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

Type II Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01020123
• Other study ID #: D1020C00009
• Status: Completed
• Phase: Phase 2
• First received: November 11, 2009
• Last updated: November 22, 2012
• Start date: October 2009
• Est. completion date: February 2011

Study information

• Verified date: November 2012
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Chile: Instituto de Salud Pública de ChileGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthMexico: Federal Commission for Protection Against Health RisksPeru: General Directorate of Pharmaceuticals, Devices, and DrugsPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRomania: National Medicines AgencySweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 530
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type II Diabetes Mellitus

Intervention

Drug:
• AZD1656
Different doses of AZD1656 administered to 5 groups of patients
• Placebo
AZD1656 placebo and glipizide placebo administered to 1 group of patients
• Glipizide
Glipizide administered to 1 group of patients

Locations

Country	Name	City	State
Chile	Research Site	Brentwood	TN
Chile	Research Site	Santiago
Chile	Research Site	Temuco
Chile	Research Site	Temuco	Novena Region
Germany	Research Site	Aschaffenburg
Germany	Research Site	Berlin
Germany	Research Site	Bochum
Germany	Research Site	Brentwood	TN
Germany	Research Site	Dortmund
Germany	Research Site	Dresden	SN
Germany	Research Site	Frankfurt
Germany	Research Site	Görlitz
Germany	Research Site	Hamburg
Germany	Research Site	Lubeck
Germany	Research Site	Magdeburg
Hungary	Research Site	Balatonfured
Hungary	Research Site	Bekescsaba
Hungary	Research Site	Dunaujvaros
Hungary	Research Site	Eger
Hungary	Research Site	Gyula
Hungary	Research Site	Kaposvar
Hungary	Research Site	Nyiregyhaza
Hungary	Research Site	St. Laurent	QC
Hungary	Research Site	Szekszard
Hungary	Research Site	Szigetvar
Hungary	Research Site	Zalaegerszeg
Latvia	Research Site	Brentwood	TN
Latvia	Research Site	Daugavpils
Latvia	Research Site	Jekabpils
Latvia	Research Site	Jelgava
Latvia	Research Site	Limbazi
Latvia	Research Site	Riga
Latvia	Research Site	Talsi
Latvia	Research Site	Valmiera
Lithuania	Research Site	Brentwood	TN
Lithuania	Research Site	Kaunas
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Brentwood	TN
Mexico	Research Site	Chiuahua
Mexico	Research Site	Cuernavaca	Morelos
Mexico	Research Site	Merida	Yucatan
Mexico	Research Site	Meridas	Yucatan
Mexico	Research Site	Monterrey
Mexico	Research Site	Monterrey	Nuevo Leon
Mexico	Research Site	San Luis Potosi
Mexico	Research Site	Zapopan	Jalisco
Peru	Research Site	Brentwood	TN
Peru	Research Site	Callao
Peru	Research Site	Lambayeque
Peru	Research Site	Lima
Peru	Research Site	Piura
Peru	Research Site	Trujillo
Poland	Research Site	Brentwood	TN
Poland	Research Site	Gdansk
Poland	Research Site	Krakow
Poland	Research Site	Kutno
Poland	Research Site	Wroclaw
Romania	Research Site	Alba Iulia	Alba
Romania	Research Site	Brentwood	TN
Romania	Research Site	Galati
Romania	Research Site	Ploiesti
Romania	Research Site	Sibiu
Romania	Research Site	Tg Mures	Mures
Romania	Research Site	Timisoara
Sweden	Research Site	Brentwood	TN
Sweden	Research Site	Huddinge
Sweden	Research Site	Lund
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Chorley
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Liverpool	Merseyside
United Kingdom	Research Site	Paignton	Devon
United Kingdom	Research Site	St. Laurent	QC
United Kingdom	Research Site	Stevenage
United Kingdom	Research Site	West Bromwich
United Kingdom	Research Site	West Lothian

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Chile,  Germany,  Hungary,  Latvia,  Lithuania,  Mexico,  Peru,  Poland,  Romania,  Sweden,  United Kingdom, 

Outcome

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