E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Type 2 diabetes |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
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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 primary objective is to determine the effect of taspoglutide in addition to standard of care on cardiovascular outcomes in type 2 diabetic subjects with established cardiovascular disease in order to rule out an unacceptable (80%) increase in cardiovascular events.
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E.2.2 | Secondary objectives of the trial |
To assess the effects of taspoglutide in addition to standard of care on: • A secondary CV composite endpoint: the individual components of the composite primary endpoint plus any revascularization procedure and hospitalization for other CV events • Each of individual components of the composite CV primary endpoint • Total mortality • Metabolic and renal function parameters |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men and women > 18 years old at screening. Women of childbearing potential will be required to use two approved birth control methods during the entire course of the study. 2. Known type 2 diabetes (T2D) or newly diagnosed T2D according to the 1997 American Diabetes Association diagnostic criteria* *Fasting plasma glucose (FPG) values ≥126 mg/dl, or symptomatic hyperglycemia and a casual glucose ≥200 mg/dl OR 2-h plasma glucose ≥200 mg/dl after a 75 g oral glucose load Diabetes may be managed with diet alone, or with any approved glucose-lowering therapies except for those listed in exclusion criteria 11 and 12. The diabetes reatment will follow the local usual standard of care 3. HbA1C ≥6.5% and ≤10% at screening 4. Body mass index (BMI) ≥ 23 kg/m2 at screening 5. Subjects with established cardiovascular (CV) disease with onset ≥1 month prior to screening and who are stable in the Investigator’s judgment, based on the presence of at least one of the following:
Documented coronary disease: • Myocardial infarction • History of coronary revascularization (percutaneous coronary interventions, coronary artery bypass graft surgery - CABG) • Documented angina pectoris with ischemic ECG changes at rest or with ischemic ECG changes on a graded exercise test, or positive cardiac imaging stress test results documenting ischemia • Angiographic or CT-imaging (e.g. MDCT/CTA) evidence of ≥ 70% narrowing of one coronary artery or ≥ 50% narrowing of two or more coronary arteries
Documented cerebrovascular disease: • History of stroke (TIA is not fulfilling this inclusion criterion) • Angiographic evidence of at least 75% narrowing of one or more carotid arteries • History of arterial revascularization Documented symptomatic peripheral arterial disease: • Current intermittent claudication and ankle-brachial index ≤0.85 and/or documented peripheral artery disease • History of intermittent claudication and previous intervention (peripheral bypass, angioplasty)
6. Ability and willingness to give written informed consent and to comply with the requirements of the study. |
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E.4 | Principal exclusion criteria |
1. Women who are currently pregnant, currently lactating, or intent to become pregnant during the study period. 2. Diagnosis of or history of: a. Type 1 diabetes mellitus, diabetes resulting from pancreatic injury, or secondary forms of diabetes, e.g., acromegaly and Cushing’s Syndrome b. Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within the past 6 months c. Severe hypoglycemia (defined as requiring third party assistance) within one month prior to screening 3. Clinically significant gastrointestinal (GI) disease, judged likely to limit tolerability of taspoglutide, such as inflammatory bowel disease, celiac disease, diabetic gastroparesis, cholelithiasis 4. History of bariatric surgery (e.g. gastric bypass or antrectomy), small or large bowel resection, or laparoscopic gastric banding, or intent to undergo any similar procedure during the study period 5. History of chronic pancreatitis or acute pancreatitis. 6. Family or personal history of medullary thyroid carcinoma. 7. Currently scheduled for cardiac surgery or arterial revascularization (carotid, coronary or peripheral) procedures 8. Current NYHA class IV heart failure or post-transplantation cardiomyopathy 9. Diagnosed and/or treated malignancy (except for basal cell skin cancer, in situ carcinoma of the cervix or in situ prostate cancer) within the past 5 years 10. Any concurrent medical condition/disorder that, in the opinion of the Investigator, is likely to: - Interfere with the subject’s ability to complete the entire study period or to participate in all aspects of the trial - Require the administration during the study of a treatment that would affect the interpretation of the efficacy and safety variables 11. Current treatment or known intolerance to exenatide or exendin-4 analogues, GLP-1 or GLP-1 analogues 12. Current treatment with insulin or insulin analogues 13. Treatment with systemic (oral or parenteral) corticosteroids for more than 7 consecutive days within 12 weeks prior to screening 14. Use of any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to screening unless local health authority guidelines mandate a longer period 15. Any of the following laboratory abnormalities at screening: a. ALT or AST > 3 times the upper limit of the normal range b. Fasting triglycerides > 5.6 mmol/L (> 500 mg/dL) 16. Glomerular filtration rate (GFR) <30 mL/min/1.73m2 estimated by the Modification of Diet in Renal Disease (MDRD) equation: GFR (mL/min/1.73 m2) = 186 x (serumcr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African-American) (Please see the following web-based GFR calculator: http://www.nkdep.nih.gov/professionals/gfr_calculators/orig_con.htm) 17. Systolic blood pressure (SBP) ≥ 180 or diastolic blood pressure (DBP) ≥ 110 mmHg at screening 18. Potentially unreliable subjects and those judged by the Investigator to be unsuitable for the study 19. History of active substance abuse (including alcohol) within the past 2 years |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the time to first occurrence of any component of a cardiovascular composite endpoint (CV death, MI, stroke, resuscitated cardiac arrest, hospitalization for unstable angina or hospitalization for heart failure) adjudicated by an independent cardiovascular event adjudication committee (CV-EAC). For this primary cardiovascular endpoint a noninferiority test will be applied to the data from the intent-to-treat (ITT) population to confirm the hypothesis that the hazard ratio comparing the taspoglutide and placebo groups falls below and excludes a 1.80 upper bound of the 95% confidence interval. Therefore, if the upper limit of the 95% CI of the HR is less than 1.80, non-inferiority will be concluded. If this initial objective is met the trial may be adapted, using existing statistical methods, with increases in the sample size and study duration in order to exclude, in sequence, a 30% increase in cardiovascular events (i.e. the upper 95% CI being less than a HR = 1.3) followed by (if met) an assessment of superiority. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Analysis of the primary composite cardiovascular outcome |
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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 | No |
E.8.1.3 | Single blind | No |
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) | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 124 |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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The end of the clinical trial is defined as the date when the requisite number of cardiovascular events positively adjudicated for the primary endpoint has occurred and all subjects have completed a minimum of 6 months of treatment. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |