E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes mellitus, type 2 (Blood Glucose Lowering Effect)/ |
|
MedDRA Classification |
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 changes in fasting plasma glucose versus baseline, following 12 weeks of oral dosing with P1736-05 versus placebo in adult subjects diagnosed with type 2 diabetes mellitus |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of P1736-05 versus placebo. To evaluate the pharmacokinetics of P1736-05 in type 2 diabetes mellitus subjects. To evaluate the effect of P1736-05, versus placebo, on glycemic and metabolic parameters following 12 weeks of treatment in adult subjects with type 2 Diabetes mellitus: Change in fasting plasma insulin levels Change in HbA1c Change in serum fructosamine Percent change in body weight Percent change in lipids (total cholesterol, HDL, LDL, triglycerides, VLDL, FFA) in fasting state Change in standard meal tolerance test variables including peak and 4 hour post prandial glucose, peak abd 4 hour post prandial insulin, glucose, insulin and C-peptide AUC's Change in Adiponectin and leptin levels |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age: 18- 70 yrs, inclusive 2. BMI: 25 - 40 kg/m2, inclusive 3. HbA1c: at screening between 6.2 and 9.5 % for subjects on antidiabetic medication and between 7 and 10% for subjects on diet and exercise 4. FPG: at randomization ≤12.5 mmol/l 5. Fasting C-peptide: at screening ≥0.16nmol/L (>0.5ng/ml) 6. For men willingness to use adequate contraception from screening until 3 months after the follow-up visit 7. For females: negative pregnancy test at screening and each admission, or of no childbearing potential (females) (a prerequisite for female subjects of childbearing potential is adequate contraception during the study and until 3 months after the follow-up visit) Postmenopausal females: postmenopausal status is usually based on history of amenorrhoea duration (no menstrual period for 24 consecutive months) 8. Has an established clinical diagnosis of stable type 2 diabetes mellitus for at least 3 months prior to the screening period; (Type 2 Diabetes Mellitus as defined by the criteria of the American Diabetes Association and recognized by World Health Organization (WHO) Expert Committee on the Diagnosis and Classification of Diabetes Mellitus [American Diabetes Association, 2006] 9. Currently on oral hypoglycemic drugs with metformin or sulfonyl urea either as monotherapy or combination therapy or Drug naive (Defined as subjects not received any pharmacological treatment for at least 12 weeks before screening and no anti diabetic agents for > 3 consecutive months any time in the past). 10. Is on a stable weight, with no more than a 4% gain or loss in the 3 months prior to screening (by history) 11. Willing to give written informed consent to participate in the study
|
|
E.4 | Principal exclusion criteria |
1. MODY (Mature Onset Diabetes of the Young), insulin dependent type 2 diabetes mellitus, or other unusual or rare forms of diabetes mellitus 2. Has had >4 episodes of severe hypoglycemia that required the assistance of another person within the past 6 months (brittle diabetes) 3. Type 2 Diabetes of more than 15 years duration prior to screening. 4. Has a history of acute metabolic diabetic complications such as ketoacidosis or hyperosmolar nonketotic coma 5. Has used insulin previously within past 3 months prior to screening 6. Has used GLP-1 analog (for example, exenatide) within 6 months prior to screening 7. Has used Thiazolidinediones or DPP4 inhibitors within 6 months prior to screening. 8. Has received any investigational drug within 60 days prior to study entry 9. Has a history of hypersensitivity or allergies to similar class of drug as the study drug, unless approved by the Investigator 10. Has a clinically significant history of substance or alcohol abuse within the past year or a current diagnosis of substance or alcohol abuse 11. Has a positive serology for an infectious disease (including HIV, Hepatitis B or C) at Screening 12. Has donated blood (≥500mL) within the three months preceding the screening period or suffered significant blood loss equal to a donor portion (approx 500mL). 13. Has history of clinically significant disease other than type 2 diabetes (endocrine, hepatic, renal, Metabolic, neurological, psychiatric, cardiovascular, pulmonary, gastrointestinal, Hematological or gynecological disease (including subjects with diabetic end organ Disease (renal, cardiac, and retinal) o Subjects with significant renal insufficiency, only one functioning kidney, history of renal transplantation, or currently receiving renal dialysis o Subjects with creatinine clearance <60 mL/min as determined by Cockcroft and Gault formula o Subjects with Serum creatinine ≥1.5 mg/dL or ≥132.6 µmol/L o Subjects with a clinically significant abnormal WBC count, thrombocytopenia, or anemia at screening o Subjects with history or presence of proliferate retinopathy, macular degeneration or edema, retinal detachment, and/or severe vision impairment (i.e. subject requires assistance in daily tasks) o Subjects with hepatic disease or clinically relevant evidence of it (i.e. values at screening and at pre-randomization of more than 2 x ULN for aspartate aminotransferase [AST], alanine aminotransferase [ALT] or values of more than 1.5 x ULN for bilirubin or alkaline phosphates. Subjects with high bilirubin associated with Gilbert’s syndrome will not be excluded o Subjects who have a history of malignancy o Subjects with cardiovascular disease within the previous 6 months prior to screening (including, but not limited to, myocardial infarction, stroke, peripheral vascular disease, ischemic changes resting ECG) o Subjects with severe and uncontrolled hypertension (blood presure above 160/100) o Subjects with a history of unhealed diabetic ulcer o Subjects with hypo or hyperthyroidism 14. Subjects who have been hospitalized for any psychiatric illness in the past year, or are diagnosed with major depression. 15. Subjects with any other clinically significant laboratory abnormality at screening 16. Has a clinical condition or receiving therapy that, in the opinion of the Investigator, would make the subjects unsuitable for study. 17. Subjects who have received in the 3 months prior to screening, any systemic glucocorticoid treatment |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the changes in fasting plasma glucose versus baseline To evaluate the effect of P1736-05, versus placebo, on glycemic and metabolic parameters following 12 weeks of treatment in adult subjects with type 2 Diabetes Mellitus: • Change in fasting plasma insulin levels • Change in HbA1c • Change in serum fructosamine • Percent change in body weight • Percent change in lipids (total cholesterol, HDL, LDL, triglycerides, VLDL, FFA) in fasting state • Change in Standard Meal Tolerance Test variables including peak and 4 hour post prandial glucose, peak and 4 hour post prandial insulin; glucose, insulin and C- peptide AUC’s • Change in Adiponectin and leptin levels AEs, vital signs, ECG parameters Physical examination clinical laboratory |
|
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 | No |
E.6.10 | Pharmacogenetic | No |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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
|
Planned study period: Q4 2009 – Q3 2010 Study will be closed for enrolling after the enrollment of 20th patient. The last visit of the last patient will be 12 weeks later (+3 days window period) this date, according with the protocol. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |