E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
|
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 |
To demonstrate the non-inferiority of taspoglutide to insulin glargine on glycemic control (as assessed by HbA1c) after 24 weeks of treatment. |
|
E.2.2 | Secondary objectives of the trial |
• To assess the effects of taspoglutide versus insulin glargine on additional parameters of glycemic control after 24 weeks. • To assess the effects of taspoglutide versus insulin glargine on body weight and cardiovascular (CV) risk factors (lipid profile) after 24 weeks. • To assess the safety and the tolerability of taspoglutide versus insulin glargine after 24 weeks. • To assess the efficacy, safety and tolerability of taspoglutide versus insulin glargine after 52 weeks and 156 weeks • To describe the pharmacokinetics of taspoglutide using a population PK approach including the influence of covariates on the PK parameters of taspoglutide after 24 weeks.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men and women aged 18 - 75 years at screening. Women of childbearing potential using two medically approved birth control methods (e.g. hormonal contraceptives, IUD, barrier contraception) must be willing to use the same methods of contraception during the whole course of the study. 2. Type 2 diabetic patients treated with a stable dose of metformin and sulphonylurea (including immediate or extend-release fixed combination) for at least 12 weeks prior to screening. The dose of metformin must be ≥ 1500 mg/day (or individual maximally tolerated dose), but no more than the maximum dose specified in the label; sulphonylurea can be at any dose. 3. Agreement that the sulphonylurea treatment must be stopped 5 days (+/- 1 day) before the start of the treatment period (Day 1). 4. HbA1c: ≥ 7.0% and ≤ 10% at screening. 5. Body mass index (BMI) > 25 (> 23 for Asians) and ≤ 45 kg/m2 at screening. 6. Stable weight ± 5% for at least 12 weeks prior to screening. 7. Fasting serum C-peptide > 1 ng/ml (≥333 pmol/L). 8. Agreement to maintain prior diet and exercise habits during the full course of the study. 9. Ability and willingness to give written informed consent and to comply with the requirements of the study.
|
|
E.4 | Principal exclusion criteria |
1. Women who are pregnant, intending to become pregnant during the study period or currently lactating females. 2. Diagnosis of or history of: • Type 1 diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes, e.g. acromegaly and Cushing’s syndrome; • Acute metabolic diabetic complications, such as ketoacidosis or hyperosmolar coma within the past 6 months. 3. Evidence of clinically significant diabetic complications. 4. Diagnosed proliferative diabetic retinopathy. 5. Clinically symptomatic gastrointestinal (GI) disease including -but not limited to- inflammatory bowel disease, celiac disease, diabetic gastroparesis, cholelithiasis. 6. History of bariatric surgery (e.g. gastric bypass or antrectomy), or small or large bowel resection. 7. History of chronic pancreatitis or idiopathic acute pancreatitis. 8. More than 3 episodes of severe hypoglycemia (defined as requiring assistance by another person) within 6 months prior to screening. 9. History of hypoglycemia unawareness. 10. Myocardial infarction (MI), coronary artery bypass surgery, post-transplantation cardiomyopathy (PTCM) or stroke within 6 months prior to screening. 11. Any abnormality in clinical laboratory tests or ECG, which precludes safe involvement in the study as judged by the Investigator. 12. Clinically relevant QTc prolongation (e.g. QTc > 480 ms), family history of Long QT Syndrome, or concomitant use of Class I anti-arrhythmic drugs (e.g. disopyramide, quinidine, procainamide, mexiletine, flecainide, propafenone). 13. Diagnosed and/or treated malignancy (except basal cell skin cancer, in situ carcinoma of the cervix, or in situ prostate cancer) within the past 5 years. 14. Known hemoglobinopathy or chronic anemia. 15. Donation of one unit (500 ml) or more blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks or a blood transfusion within the past 8 weeks. 16. Any concurrent medical condition/disorder that, in the opinion of the Investigator is likely: • to interfere with the patient’s ability to complete the entire study period or to participate in all aspects of the trial; • to require, during the study, the administration of a treatment that would affect the interpretation of the efficacy and safety data. 17. Contraindications and warnings according to the country specific label information for metformin and insulin glargine not listed in the other exclusion criteria. 18. Known hypersensitivity to metformin or insulin glargine or any of their components. 19. Treatment with any oral anti-diabetic medication (other than metformin and sulphonylureas), and/or herbal/over-the-counter preparations that may affect glycemic control within 12 weeks prior to screening. 20. Treatment with exenatide or exendin analogues, GLP-1 or GLP-1 analogues at anytime during the past. 21. Treatment with insulin (except during pregnancy) for more than one week, within 6 months prior to screening. 22. Chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 4 weeks prior to screening. 23. Treatment with weight lowering agents (e.g. orlistat, sibutramine, rimonabant, phentermine) during the last 12 weeks prior to screening. 24. History of unstable hypertension (SBP > 170 mmHg and/or DBP > 105 mmHg), within the past 12 weeks prior to screening. 25. Treatment with anti-hypertensive medications which are not on a stable dose for at least 4 weeks prior to baseline. 26. Treatment with lipid lowering medications which are not on a stable dose for at least 8 weeks prior to screening. 27. Treatment with thyroid hormones which are not on a stable dose for at least 12 weeks prior to screening. 28. Use of investigational drugs within 30 days or 5 half-lives (whichever is longer) prior to screening unless local Health Authority guidelines mandate a longer period. 29. Any of the following laboratory abnormalities at screening: • ALT and/or AST > 3 times the upper limit of the normal range; • Serum creatinine levels ≥ 132 µmol/L (≥ 1.5 mg/dL) males, ≥ 123 µmol/L (≥ 1.4 mg/dL) females; • Fasting triglycerides > 5.6 mmol/L (> 500 mg/dL); • Clinically significant TSH outside the normal range. 30. History of active substance abuse (including alcohol) within the past 2 years. 31. Potentially unreliable patients and those judged by the Investigator to be unsuitable for the study.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
All endpoints will be assessed at the end of the 24 weeks treatment period. Primary endpoint: Absolute change from baseline in HbA1c.
|
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | No |
E.8.1.4 | Double blind | No |
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 | No |
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.8.5.1 | Number of sites anticipated in the EEA | 79 |
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 | 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
|
The end of the clinical trial is defined as the date of the last visit of the last patient finishing the trial (including any follow up visit required). Last Patient Last Visit is either the date of the last visit of the last patient to complete the study, or the date at which the last data point from the last patient, which was required for statistical analysis (i.e. key safety and efficacy results for decision making), was received, whichever is the later date.
|
|
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 | 11 |
E.8.9.1 | In the Member State concerned days | |
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 | 11 |