E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed Type 2 Diabetes Mellitus. |
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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 determine the glucose lowering effects of PPM-204 in subjects with type 2 diabetes mellitus. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and pharmacokinetics (PK) of multiple oral doses of PPM-204 in subjects with type 2 diabetes mellitus. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. A signed and dated informed consent form. 2. Men or women, aged 30 to 80 years inclusive on study day 1. 3. Men who agree to participate in this study must understand that there is a riskwhen taking a drug whose effect on a fetus is unknown and must use adequatebarrier contraception (such as, condoms) during the study period and for at least60 days after study discharge. 4. Women of nonchildbearing potential may be included if they are either surgicallysterile (hysterectomy and/or oophorectomy) or postmenopausal (defined as atleast 12 months of spontaneous amenorrhea). If menopausal status is uncertain, aFSH level of >= 40 mIU/mL will allow enrollment. Women who are surgicallysterile must provide documentation by a physician of the procedure and must havea negative serum pregnancy test result within 48 hours before the administrationof test article. 5. Diagnosed with type 2 diabetes at least 4 weeks prior to study day 1. 6. Subjects who have never received any pharmacologic treatment for diabetes withthe sole exception of subjects who received a single short term insulin treatmentperiod, administered for no longer than two weeks and discontinued at least threemonths before study day 1, or: subjects who had received oral hypoglycemictreatment for less than 1 month and that treatment ended at least 4 weeks beforestudy day 1, or: subjects who had received oral hypoglycemic treatment for morethan 1 month but less than 1 year and that treatment ended at least 8 weeks beforestudy day 1. 7. HbA1C >= 6.8% and =< 10.5%, C-peptide of >= 2.0 ng/mL [0.66 nmol/L], fastingplasma glucose (FPG) of >= 140 mg/dL [7.7 mmol/L] and =< 280 mg/dL [15.5mmol/L]. 8. Body mass index in the range of 22 to 41 kg/m2 and body weight >= 50 kg. 9. Subjects should be on a stable exercise regimen and a weight-maintenance diet asrecommended by the American Diabetes Association or the European Associationfor the Study of Diabetes for at least 10 days before study day 1. 10. Have a high probability for compliance with and completion of the study. |
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E.4 | Principal exclusion criteria |
1. Presence or history of any disorder that may prevent the successful completion ofthe study. 2. Any significant cardiovascular disease other than that specified in the inclusioncriteria, or any hepatic, renal, respiratory, gastrointestinal, endocrine (except type2 diabetes mellitus), immunologic, dermatologic, hematologic, neurologic,musculoskeletal, rheumatic, or psychiatric disease or psychological disorder. 3. History or current evidence of congestive heart failure (CHF). 4. History or current evidence of coronary artery disease (CAD), such as myocardialinfarction (MI), angioplasty, or CABG, all within 1 year before study day 1. 5. Joint National Committee VII (JNC-VII) stage 2 hypertension (>=160 systolic or >=100 diastolic). 6. History or current evidence of peripheral edema, venous insufficiency, peripheralvascular disease (PVD), or clinically important neuropathy. 7. History of stroke. 8. History or current evidence of hematuria, kidney stones, or renal insufficiency(creatinine >= 2.0 mg/dL [162.8 μmol/L]). 9. History or current evidence of thyroid abnormalities. 10. History of active asthma within the last 5 years. 11. History of non-steroidal anti-inflammatory drug (NSAID) induced bronchospasm. 12. History or current evidence of proliferative retinopathy. 13. Any blood or blood product transfusion within 90 days before study day 1. 14. Any surgical or medical condition that may interfere with the absorption,distribution, metabolism, or excretion of the test article.15. Acute disease state (eg, nausea, vomiting, fever, diarrhea) within 7 days beforestudy day 1. 16. History of drug abuse within 1 year before study day 1. 17. History of alcohol abuse or excessive consumption within 1 year before study day1. 18. Any clinically important deviation from normal limits in physical examination,vital signs, ECGs, or clinical laboratory test results except per the criteria notedbelow under # 19, 20, 21, 22, and 23. 19. Serum creatinine >= 2.0 mg/dL [162.8 μmol/L]. 20. ALT or AST >= 1.5 times upper limit of normal (ULN). 21. Abnormal total bilirubin (> ULN), unless the elevation is due to Gilbert’ssyndrome. 22. Total fasting triglycerides >= 500 mg/dL [5.6 mmol/L]. 23. Abnormal troponin and/or CPK MB at screening. 24. Positive serologic findings for human immunodeficiency virus antibodies,hepatitis B surface antigen, and/or hepatitis C virus antibodies. 25. Weight loss or gain of > 10% within 90 days before study day –1.Allergies and Adverse Drug Reactions 26. History of any clinically important allergy. 27. History of any hypersensitivity to sulfonamides. 28. History of any allergy to NSAIDs. 29. Use of any investigational drug or prescription drug (other than those identified insection 14.1) within 30 days before study day 1. 30. Use of insulin or any oral hypoglycemic agents (with the exception of test article)is prohibited throughout the study, except for emergency treatment of subjectswho meet “escape criteria” as depicted in the protocol under section 18.6. 31. History of insulin use, except for short-term administration of insulin for amaximum of one period no longer than two weeks, that was discontinued at leastthree months before study day 1, as described in inclusion criterion #6 above. 32. Use a beta-blockers, alpha-blockers, diuretics (except thiazide diuretics if theregimen was stable for at least 3 months before screening), or fibrates isprohibited throughout the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy pharmacodynamic variables are changes from baseline of fasting plasma glucose (FPG) and mean plasma glucose during oral glucose tolerance test (OGTT) and insulin at day 28 (end of treatment).
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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 | Information not present in EudraCT |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.6 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 | Information not present in EudraCT |
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 study is the last visit of the last subject. |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 8 |