| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with Type 2 diabetes |
|
| 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 |
|
| 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 evaluate the efficacy of taspoglutide on glycemic control (as assessed by HbA1c) compared to pioglitazone after 24 weeks of treatment in 648 patients with type 2 diabetes mellitus inadequately controlled with sulfonylurea (SU) monotherapy or metformin plus sulfonylurea combination therapy |
|
| E.2.2 | Secondary objectives of the trial |
• To assess the effects of taspoglutide versus pioglitazone on additional parameters of glycemic control including fasting plasma glucose, the proportion of patients target
HbA1c levels of <7.0% and <6.5%, the proportion of patients requiring rescue medication and time-toglycemic rescue
• To assess the effects of taspoglutide versus pioglitazone on body weight loss parameters including change in body weight, percentage of patients who achieve a body weight loss of at least 5% or 10%, and waist and hip circumferences
• To assess the safety (including rates hypoglycemic events) and tolerability of taspoglutide versus pioglitazone up to 104 weeks treatment
• 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 |
|
| 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 approved birth control method (e.g. hormonal contraceptives, IUD, barrier contraception) must be willing to use two approved methods of contraception during the entire course of the study.
2. Type 2 diabetes patients treated with stable sulfonylurea monotherapy or metformin plus sulfonylurea combination therapy for at least 12 weeks prior to Screening. Sulfonylurea (SU) dosage should be the maximum effective dose which is defined as at least half of the maximum country-specific labelled dose, except for cases in which the highest individually tolerated dose is lower. Metformin dose should be ≥1500 mg/day (or individual maximally tolerated dose), but no more than the maximum dose specified in the label.
3. Agreement to maintain the SU dosage except as modified by the investigator.
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. Agreement to maintain prior diet and exercise habits throughout the entire study.
8. 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
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, e.g. known proliferative retinopathy
4. Clinically symptomatic gastrointestinal (GI) disease including but not limited to inflammatory bowel disease, celiac disease, diabetic gastroparesis, and 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. Record of more than 3 episodes of severe hypoglycemia (defined as requiring assistance by another person) within 6 months before Screening
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 complete the entire study period or to participate in all aspects of the trial (including and not restricted to the ability to perform the SMBG)
• 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 sulfonylurea, metformin (if administered as background therapy) and pioglitazone, not listed in the other exclusion criteria
15. Known hypersensitivity to sulfonylurea, metformin (if administered as background therapy) or pioglitazone or any of their components
16. Treatment with any oral anti-diabetic medication (other than metformin and sulfonylurea), and/or herbal/over-the-counter preparations that may affect glycemic control within 12 weeks prior to Screening
17. Treatment with exenatide or exendin analogues, or GLP-1 analogues at anytime during the past
18. Chronic oral or parenteral corticosteroid treatment (>7 consecutive days of treatment) within 4 weeks prior to Screening
19. Treatment with weight lowering agents (e.g. orlistat, sibutramine, phentermine) within 12 weeks prior to Screening
20. Documented values of blood pressure above SBP > 170 mmHg and/or DBP > 105 mmHg within 12 weeks prior to Screening
21. Treatment with anti-hypertensive medications which are not on a stable dose for at least 4 weeks prior to Baseline
22. Treatment with lipid lowering medications which are not on a stable dose for at least 8 weeks prior to Screening
23. Treatment with thyroid hormones which are not on a stable dose for at least 12 weeks prior to Screening
24. 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
25. 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
26. History of active substance abuse (including alcohol) within the past 2 years.
27. Potentially unreliable patients and those judged by the Investigator to be unsuitable for the study.
28. History or diagnosis of post-transplantation cardiomyopathy (PTCM) any time in the past
29. Family or personal history of medullary thyroid carcinoma |
|
| 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. |
|
| 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 | Yes |
| 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 | 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 |
|
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 49 |
| 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
| |
| 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 | |
| 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 |
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