A 4-WEEK RANDOMIZED, PARALLEL, DOUBLE-BLIND, PLACEBO-CONTROLLED MULTICENTER STUDY OF THE PRELIMINARY EFFICACY, SAFETY, AND PHARMACOKINETICS OF PPM-204 ADMINISTERED ORALLY TO TREATMENT-NAÏVE SUBJECTS WITH TYPE II DIABETES MELLITUS

Conditions: ewly diagnosed Type 2 Diabetes Mellitus.

Registration Number: EUCTR2005-004227-19-DE

Lead Sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 108

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the glucose lowering effects of PPM-204 in subjects with type 2 diabetes mellitus.;Secondary Objective: To assess the safety and pharmacokinetics (PK) of multiple oral doses of PPM-204 in subjects with type 2 diabetes mellitus.;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).<br>

Secondary Outcome Measures

Name	Time	Method

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