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 | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II 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 difference in glycemic profiles between vildagliptin and glimepride in patients with type 2 diabetes, using a CGM device. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the glucose fluctuation (Mean Amplitude of Glycemic Excursions , MAGE) before and during treatment with vildagliptin and glimepride based on 24-hr continuous glucose monitoring • To explore the correlation between 8-iso-prostaglandin F2α and glucose fluctuation (MAGE)
See protocol for exploratory objectives
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent must be obtained before any assessment is performed. • Able to communicate well with the investigator, to understand and comply with the requirements of the study. • Patients must be willing to comply with dietary recommendations throughout the study • Willingness to perform required study and data collection procedures and adhere to operating requirements CGMS iPro Systems • Willingness to perform at least 4 capillary blood glucose tests per day while wearing the Guardian REAL-Time and iPro Systems • Type 2 diabetics stabilized on metformin monotherapy (stable dose for at least 4 weeks prior to Screening). The metformin dose should not be expected to change during the course of the study • Agreement to maintain the same dose of metformin throughout the study. • Patients must be diagnosed with type 2 diabetes mellitus at least 3 months prior to screening. Anti-GAD antibodies will be determined during the screening period. Patients with a positive anti-GAD antibodies assay will not be enrolled. • HbA1c 7.0~8.5% % at screening • Male and female patients, age 18 to 70years of age inclusive • Female patients of childbearing potential must be using two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the study, through study completion. • Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by a plasma FSH level (reference local lab value or >40 IU/L) at screening. • Female patients who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF. • All female patients must have negative pregnancy test results at screening and at each baseline. • Body mass index (BMI) within the range of 20 -40 kg/m2 at screening. See Appendix 4 of this protocol for BMI ranges. • Patients must be willing using the e-diary to provide input items to assess the frequency, severity and impact of hypoglycemia (provided that the questionnaire is endorsed by GCT and can be delivered timely) • At screening and baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three (3) minutes and again when required after three (3) minutes in the standing position. Sitting vital signs should be within the normal range: • oral body temperature between 35.0-37.5 °C systolic blood pressure, 90-140 mm Hg diastolic blood pressure, 50-90 mm Hg pulse rate, >=50 - 90 bpm • When blood pressure and pulse are taken after at least 3 minutes standing, there should be no more than a 20 mm Hg drop in systolic or 10 mm Hg drop in diastolic blood pressure and increase in heart rate (>20 bpm) (compared to the sitting results) associated with clinical manifestation of postural hypotension. Any subject exhibiting clinical manifestations of postural hypotension should be excluded.
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E.4 | Principal exclusion criteria |
• Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations. • Use of any other antidiabetic agents (including sulfonylureas, thiazolidinediones, repaglinide, netaglinide, exenatide, liruglutide, sitagliptin, saxagliptin and insulin) other than stable dose of metformin. • Use of any drugs that induce or inhibit CYP2C9 isozyme activity, including but not limited to Rifampin , fluconazole, fluvoxamine, gemfibrozil and voriconazole amiodarone, fluorouracil, metronidazole, miconazole, sulfamethoxazole barbiturates and cambamazepine • History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes • History of tape allergies that have not been resolved • Skin abnormality (e.g. psoriasis, rash, staphylococcus infection) that has not been resolved and would inhibit them from wearing the sensors • Significant unstable concomitant disease or complications of diabetes • Significant illness unresolved within two (2) weeks prior to initial dosing and/or acute infection(s) which may affect blood glucose control within 4 weeks prior to screening • Evidence of clinically significant diabetic organ disease (renal, retinal, neurological, vascular) or complications (e.g., symptomatic autonomic neuropathy or gastroparesis) that would preclude study participation • Patients with second degree AV block (Mobitz 1 and 2); patients with third degree AV block • Recent (within the last three [3] years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc). • Fasting triglycerides >5.1 mmol/L (>450 mg/dL) within 4 weeks prior to screening • Treatment with systemic steroids and/or on an unstable dosage of thyroid hormone • Hemoglobin levels <11.0 g/dl for females and <12.0 g/dl for males at screening. • CPK >1.5 x ULN at screening and baseline • A history of: • Type 1 diabetes mellitus, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly • Ketoacidosis and/or lactic acidosis • Peripheral vascular disease • Clinically significant ECG abnormalities and/or prolonged QTc interval > 450 msec (male); QTc interval > 470 msec (female) • Immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result. • A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. • Drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening and/or at baseline. • Migraine, cluster or vascular headaches. • Multiple and recurring allergies or allergy to the investigational compound/compound class being used in this study. • Any of the following within the past 6 months: • Myocardial infarction (MI) (if the ECG at Screening reveals patterns consistent with a MI patients will be excluded) • Coronary artery bypass surgery • Unstable angina • Stroke • Congestive heart failure NYHA class III or IV • Use of class Ia, Ib, Ic or III anti-arrhythmic. • Recent (within the last three [3] years) and/or recurrent history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
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E.5 End points |
E.5.1 | Primary end point(s) |
assessment of glucose profiles and calculation of glucose fluctuation (MAGE) |
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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 | No |
E.6.5 | Efficacy | No |
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 | 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 | 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 | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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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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 | 5 |
E.8.9.1 | In the Member State concerned days | 0 |