A 4-month, Randomized, Double-blind, Placebo- and Active-Controlled, Multi-centre, Parallel-Group study to Evaluate Efficacy, Safety and Tolerability of AZD1656 as Add-on Treatment to Metformin in Type 2 Diabetes Mellitus Patients

• Conditions: Type 2 diabetes mellitus patients on metformin treatment; MedDRA version: 12.0Level: LLTClassification code 10067585Term: Type 2 diabetes mellitus; MedDRA version: 12.0Level: PTClassification code 10067585Term: Type 2 diabetes mellitus

• Registration Number: EUCTR2009-012612-41-LV
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-08-24
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 540

Inclusion Criteria

1.Provision of informed consent prior to any study specific procedures.
2.Male or female of non-childbearing potential (postmenopausal, and/or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy/tubal ligation) aged = 18. Women will be defined as postmenopausal if last menstruation period was >1 year ago and serum FSH and LH are within the postmenopausal range, or if age >50 years and with last menstruation period >2 years ago.
3.Body mass index between = 19 and = 42 kg/m2.
4.Clinical diagnosis of T2DM.
5.Treated with maximally tolerated dose of metformin (= 1500mg/day) for at least 10 weeks prior to enrolment.
6.Patients with HbA1c = 7.5 but = 10% at enrolment visit (Visit 1) (HbA1c value according to international DCCT standard and obtained from the central laboratory used in the study) can enter cohort 1. Patients with HbA1c between >10 % and <12 % can enter the open-label arm with AZD1656 (cohort 2)
7.Patients must have taken at least 75% of their metformin tablets during the run-in period (ie, from Visit 2 to Visit 3).

For inclusion in the optional genetic research, patients must fulfil all of the inclusion criteria described above and:
•Provide informed consent for the genetic sampling and analyses.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients should not enter the study if any of the following exclusion criteria are fulfilled
1.Clinical diagnosis of Type 1 diabetes.
2.Positive test for Hepatitis B surface antigen or antibodies to HIV virus or antibodies to Hepatitis C virus. Results obtained from the central laboratory will be utilised.
3.Participation in weight loss programme (other than the lifestyle advice normally given to T2DM patients) or use of weight loss drugs (OTC or prescriptions) in the last 3 months
4.Participation in another clinical trial within 30 days prior to enrolment.
5.Unwilling or unable to perform self-monitoring of plasma glucose at home according to protocol.
6.Significant cardiovascular event within the last 6 months prior to enrolment (eg, myocardial infarction/acute coronary syndrome, revascularisation procedure, stroke or transient ischaemic attack) or heart failure New York Heart Association (NYHA) class III-IV.
7.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) laboratory results >3xULN at enrolment, obtained from the central laboratory used in the study.
8.Haemoglobin laboratory results <115 g/L at enrolment, obtained from the central laboratory used in the study.
9.History of psychiatric or somatic disease/condition (eg, gastrointestinal disease) that may interfere with the objectives of the study, as judged by the investigator.
10.History or ongoing symptoms/signs of severe allergy/hypersensitivity as judged by the investigator.
11.Known allergy to glipizide.
12.History of malignancy within the last 5 years, excluding successful treatment of basal or squamous cell skin carcinoma or in-situ carcinoma of the cervix.
13.Impaired renal function in terms of GFR<60 ml/min, based on Modification of Diet in Renal Disease Study Group (MDRD) calculationa.
14.Past or present alcohol or drug abuse within the last 5 years or positive test in drugs of abuse screens.
15.SBP >160 mmHg or DBP >95 mmHg at enrolment/screening.
16.Treatment with any other anti-diabetic agent than metformin during the last 10 weeks prior to enrolment/screening.
17.Proliferative retinopathy or other significant diabetes complications as judged by the investigator.
18.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.
19.Use of anabolic steroids and systemic treatment with glucosteroids within 3 months before enrolment. Inhalation steroid treatment allowed.
20.Blood loss in excess of 450 mL 3 months prior to enrolment.
21.Intake of another investigational drug within 30 days (or at least 5 t1/2 of the drug, if longer than 30 days) before enrolment.
22.Prior exposure to GKAs.
23.Involvement in the planning and conduct of the study or staff at the investigational site.
24.Any other condition prohibiting the patient from participating in the study according to the protocol as judged by the investigator.
25.Previous bone marrow transplant (applicable only for genetic sampling).
26.Whole blood transfusion within 120 days of the date of genetic sample collection (applicable only for genetic sampling).
27.Unable or unwilling to use basal night-time insulin as rescue treatment during the study period in case of hyperglycaemia.
Procedures for withdrawal of incorrectly enrolled patients are presented in Section 1.1.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified