| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Men or women diagnosed with type 2 diabetes and treated with diet alone or on treatment with a single oral anti diabetic agent or low doses of two agents, and with diabetic dyslipidaemia; ie low HDL-C. | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10045242 | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | The two primary objectives of this study are to assess whether tesaglitazar is superior to metformin and non-inferior to metformin combined with fenofibrate in increasing high density lipoprotein-cholesterol (HDL-C) in patients with type 2 diabetes and low HDL-C on a fixed background therapy with a statin, as determined by the change in HDL-C from baseline (visit 5) to the end of the 24-week randomised treatment period (visit 14). | |
| E.2.2 | Secondary objectives of the trial | To compare the effects of tesaglitazar versus metformin and versus metformin combined with fenofibrate in improving lipids and lipoproteins in patients with type 2 diabetes and low HDL-C on a fixed background therapy with a statin after a 24-week randomised treatment period by evaluation of:
To compare the effects of tesaglitazar versus metformin and versus metformin combined with fenofibrate on risk markers for cardiovascular disease
To compare the effects of tesaglitazar versus metformin and versus metformin combined with fenofibrate on central obesity (waist/hip ratio)
To evaluate the pharmacokinetics of tesaglitazar
To evaluate the safety and tolerability of tesaglitazar
| |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | Inclusion criteria at enrolment (visit 1):
1.Provision of a written informed consent at visit 1
2.Men or women who are 18 years of age or older at time of consenting upon visit 1
3.Female patients post menopausal, hysterectomized or if of childbearing potential using a reliable method of birth control.
4.Diagnosed with type 2 diabetes
5.Treated with diet alone or treatment with a single oral anti-diabetic agent or low doses of two oral anti-diabetic agents. All anti-diabetic medications are to be discontinued at visit 1. Treatment with lipid lowering medication, including statins, must be discontinued at visit 1.
Inclusion criteria at placebo run-in (visit 2, lab values from visit 1):
6.For patients <30 years old C-peptide concentrations have to be >0.8 ng/mL, 0.26 nmol/L
7.HbA1c equal to or over 7 % for patients not on any anti-diabetic drug for 12 weeks prior to visit 1. No lower HbA1c-limit for patients treated with oral anti-diabetic drug(s) within 12 weeks prior to visit 1.
8.HbA1c equal to or lower then 10%
9.FPG equal to or lower then 13.3 mmol/L, 240 mg/dL
10.HDL-C equal to or lower then 40 mg/dL (equal to or lower then 1.03 mmol/L) for males and equal to or lower then 50 mg/dL (1.29 mmol/L) for females
Inclusion criteria at randomisation (visit 5, lab values from visit 3 and 4):
11.HbA1c equal to or higher then 7 % for patients not on any anti-diabetic drug for 12 weeks prior to visit 1. No lower HbA1c-limit for patients treated with oral anti-diabetic drug(s) within 12 weeks prior to visit 1.
12.HbA1c equal to or lower then 10%
13.Mean FPG from two measurements (lab values from visit 3 and 4) £13.3 mmol/L, 240 mg/dL
14.HDL-C equal to or lower then 40 mg/dL (1.03 mmol/L) for males and equal to or lower then 50 mg/dL (1.29 mmol/L) for females | |
| E.4 | Principal exclusion criteria | 1.Type 1 diabetes, history of diabetic ketoacidosis, or corticosteroid-induced type 2 diabetes
2.Active arterial disease such as unstable angina, myocardial infarction, transient ischaemic attack, cerebrovascular accident, myocardial or peripheral vascular disease, revascularization or angioplasty within 24 weeks prior to visit 1
3.NYHA heart failure Class III or IV, or unstable Class I or II as judged by the investigator. For definitions see Appendix F.
4.History of thyroid ophthalmopathy
5.History of malignancy within the last 5 years, excluding successful treatment of basal or squamous cell skin carcinoma
6.History of blood lipid induced eruptive xanthomas or hypertriglyceridaemia induced pancreatitis
7.Pregnant or breastfeeding patients
8.Suspicion that the patient is infected according to world health organisation (WHO) risk categories 2 to 4 (See Appendix H)
9.Treatment with chronic insulin, within 24 weeks prior to visit 1 (however, one temporary period of daily insulin injections no longer than 7 days is allowed)
10.Treatment with combination therapy (i.e. two anti diabetic agents, except low doses of two agents, see Section 3.7) within 12 weeks prior to visit 1
11.Treatment with a thiazolidinedione within 4 weeks prior to visit 1
12.Treatment with fibrates, within 4 weeks prior to visit 1
13.Treatment with glucocorticoids (equivalent to oral prednisolon >10 mg per day), within 4 weeks prior to visit 1
14.Treatment with probenecid that cannot be stopped at visit 1
15.History of hypersensitivity or intolerance to any PPAR agonist
16.Pre-existing medical conditions that is contraindicated for the use of fenofibrate
17.Intolerance to metformin at any time in the past, or pre-existing medical conditions that is contraindicated for the use of metformin
18.Intolerance to an HMG-CoA reductase inhibitor (statin) at any time in the past, or pre-existing medical conditions that is contraindicated for the use of statins
19.History of drug-induced myopathy or drug-induced CK elevation
20.History of drug-induced liver enzyme elevations
21.History of drug-induced neutropenia
22.History of alcohol or drug abuse within the last 5 years
23.Other serious or unstable medical or psychological condition identified in the patient’s medical history that, in the judgement of the investigator, would compromise the patient’s safety or successful participation in the Clinical Study
24.Receiving any investigational product in other clinical studies within 12 weeks prior to visit 1
25.Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the investigational site)
26.Previous enrolment or randomisation of treatment in the present study
Exclusion criteria at run-in (visit 2, lab values from visit 1)
27.Any clinically significant abnormality identified on physical examination, laboratory tests or ECG, which in the judgement of the investigator would compromise the patient’s safety or successful participation in the study
28.NYHA heart failure Class III or IV, or unstable Class I or II as judged by the investigator. For definitions see Appendix F.
29.Fasting TG >7.0 mmol/L, 620 mg/dL
30.Hb <90 g/L, 9 g/dL
31.ANC <1.0 x 109/L
32.Any of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP) >2.5 times the upper limit of normal
33.Total bilirubin above the upper limit of normal unless exclusively caused by Gilbert’s syndrome
34.Creatinine above the upper limit of normal
35.CK >3 times the upper limit of normal
Exclusion criteria at randomisation (visit 5, lab values from visit 4)
36.Any clinically significant abnormality identified on physical examination, laboratory tests or ECG, which in the judgement of the investigator would compromise the patient’s safety or successful participation in the Clinical Study
37.NYHA heart failure Class III or IV, or unstable Class I or II as judged by the investigator. For definitions see Appendix F.
38.Other serious or unstable medical or psychological condition identified on medical history that, in the judgement of the investigator, would compromise the patient’s safety or successful participation in the Clinical Study
39.High blood pressure (mean diastolic BP >120 mmHg) or malignant hypertension
40.Hb <90 g/L, 9 g/dL
41.ANC <1.0 x 109/L
42.Any of ALT, AST or ALP >2.5 times the upper limit of normal
43.Total bilirubin above the upper limit of normal unless exclusively caused by Gilbert’s syndrome
44.Creatinine above the upper limit of normal
45.CK >3 times the upper limit of normal
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | Primary outcome variable:
-Change in HDL-C from baseline (visit 5) to the end of the randomised treatment period (visit 14)
| |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | Yes |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | | End of the study is defined as date of database lock, which is the time point after which no subject will be exposed to study related activities. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
