E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10012601 |
E.1.2 | Term | 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 |
To assess the efficacy of taspoglutide based on glycemic control (as assessed by HbA1c) after 24 weeks of treatment in patients with type 2 diabetes mellitus inadequately controlled with metformin, thiazolidinedione or a combination of metformin and thiazolidinedione compared with exenatide BID. |
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E.2.2 | Secondary objectives of the trial |
•Absolute/percentage change from baseline in fasting plasma glucose (FPG). •Absolute/percentage change from baseline in body weight. •Responder rates, defined as target HbA1c: ≤ 7.0 %, ≤ 6.5%. •Beta cell function (indexed by fasting pro-insulin concentration, fasting pro-insulin/insulin ratio, HOMA-B). •Meal test in a subset of patients: change in glucose, insulin, C-peptide, glucagon values (7 time-points over 3 hours). •To assess the safety and tolerability of taspoglutide versus exenatide BID. •To describe the pharmacokinetics of taspoglutide and to estimate between-patient variability using a population PK approach, exploring and quantifying the potential influence of covariates that contribute significantly to the between-patient differences in PK parameters of taspoglutide.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Skin testing procedure (substudy under the main protocol)
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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. Patients with type 2 diabetes on metformin > 1500 mg/day and/or pioglitazone ≥ 30 mg/day or rosiglitazone ≥ 4 mg/day (in the countries where the combination of thiazolidinediones and exenatide is approved) or the maximum dose specified in the label for all the above compounds on stable dose for at least 12 weeks, prior to screening. 3. HbA1c: ≥ 7.0% and ≤10% at screening 4. Body mass index (BMI) ≥ 25 (>23 for Asians) and ≤ 45 kg/m2 at screening. 5. Stable weight ± 5% for at least 12 weeks prior to screening. 6. Agreement to maintain prior diet and exercise habits during the full course of the study. 7. 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 pregnant, intending to become pregnant during the study period or currently lactating females. 2. Diagnosis of or history of: a. Type 1 diabetes, 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. 3. Evidence of clinically significant diabetic complications. 4. Clinically symptomatic gastrointestinal (GI) disease including inflammatory bowel disease, celiac disease, diabetic gastroparesis, cholelithiasis. 5. History of bariatric surgery (e.g. gastric bypass or antrectomy) or small or large bowel resection. 6. History of chronic pancreatitis or idiopathic acute pancreatitis. 7. Myocardial infarction (MI), coronary artery bypass surgery, post-transplantation cardiomyopathy (PTCM) or stroke within the past 6 months. 8. Any abnormality in clinical laboratory tests or ECG, which precludes safe involvement in the study as judged by the Investigator. 9. Clinically relevant QTc prolongation (e.g. QTc > 480 ms), family history of Long QT Syndrome, or concomitant use of Class I Antiarrythmic drugs (e.g. disopyramide, quinidine, procainamide, mexiletine, flecainide, propafenone). 10. 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. 11. Known hemoglobinopathy or chronic anemia. 12. 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. 13. Any concurrent medical condition/disorder that, in the opinion of the Investigator is likely: - to interfere with the patient’s ability 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. 14. Contraindications and warnings according to the country specific label information for metformin, pioglitazone, rosiglitazone and exenatide not listed in the other exclusion criteria. 15. Known hypersensitivity to pioglitazone, rosiglitazone or metformin or any of their components. 16. Known hypersensitivity to exenatide or exendin analogues. 17. Treatment with any oral anti-diabetic medication (other than metformin, thiazolidinediones) and/or herbal/over-the-counter preparations that may affect glycemic control within 12 weeks prior to screening. 18. Treatment with exenatide or exendin analogues, GLP-1 or GLP-1 analogues at anytime during the past. 19. Treatment with insulin (except during pregnancy) for more than one week within 6 months prior to screening. 20. Chronic oral or parenteral corticosteroid treatment (>7 consecutive days of treatment) within 4 weeks prior to screening. 21. Treatment with weight lowering agents (e.g. orlistat, sibutramine, rimonabant, phentermine) during the last 12 weeks prior to screening. 22. History of unstable hypertension (SBP > 170 mmHg and/or DBP > 105 mmHg), within the past 12 weeks prior to screening. 23. Treatment with anti-hypertensive medications which are not on a stable dose for at least 4 weeks prior to Baseline. 24. Treatment with lipid lowering medications which are not on a stable dose for at least 8 weeks prior to screening. 25. Treatment with thyroid hormones which are not on a stable dose for at least 12 weeks prior to screening. 26. 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. 27. Any of the following laboratory abnormalities at screening: a. ALT and/or AST > 3 times the upper limit of the normal range or any AST and/or ALT range contra-indicated based on pioglitazone or rosiglitazone label in the country of the study; b. serum creatinine levels ≥ 132 µmol/L (1.5 mg/dL) males, ≥ 123 µmol/L (1.4 mg/dL) females; c. fasting triglycerides > 5.6 mmol/L (> 500 mg/dL); d. clinically significant TSH outside the normal range. 28. History of active substance abuse (including alcohol) within the past 2 years. 29. Potentially unreliable patients and those judged by the Investigator to be unsuitable for the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the absolute change from baseline in HbA1c (%) after 24 weeks (one week after last injection). |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 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.
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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 | 3 |
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 years | 3 |