A phase 2, 12-week randomized, double-blind, placebo-controlled, study to evaluate safety, tolerability, pharmacokinetic and effect on glycemic control of p1736-05 in subjects with type 2 diabetes mellitus
1. Age : at screening > 35 and < 65 yrs.
2. BMI : at screening 23 - 40 kg/m2, (weight in Kilogram/(Height in m)2) inclusive.
3. HbA1c : at screening and pre-randomization between 7.5 and 10%.
4. Fasting Plasma Glucose (FPG ) : at screening between 130 mg/dl to 250 mg/dl.
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 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 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. Subjects should be Drug naive (Defined as subjects who have not received any pharmacological treatment for at least 12 weeks before screening and no anti-diabetic agents for ≥ 4 consecutive months any time in the past).
10. Is on a stable weight level, 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.
ExclusionCriteria
Details
1.MODY (Mature Onset Diabetes of the Young), or other unusual or rare forms of diabetes mellitus, type I diabetes mellitus.
2.Type 2 Diabetes of more than 8 years duration prior to screening.
3.Has a history of acute diabetic complications such as ketoacidosis or hyperosmolar nonketotic coma within 6 months prior to screening.
4.Has a history of insulin use within 6 months prior to screening.
5.Has used oral anti-diabetic medications within 3 months prior to screening.
6.Has received any investigational drug within 60 days prior to screening.
7.Has a history of hypersensitivity or allergies to similar class of drug as the study drug, unless approved by the Investigator.
8.Has a clinically significant history of substance or alcohol abuse within the past year or a current diagnosis of substance or alcohol abuse.
9.Has a positive serology for Hepatitis B or C at screening or known history of HIV at screening.
10.Has donated blood (≥500mL) within the 3 months preceding the screening period or suffered significant blood loss equal to a donor portion (approx 500mL).
11.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)
oSubjects with significant renal insufficiency, only one functioning kidney, history of renal transplantation, or currently receiving renal dialysis.
oSubjects with serum creatinine ≥1.5 mg/dL or ≥132.6 µmol/L
oSubjects with a clinically significant abnormal WBC count, thrombocytopenia, or anemia at screening.
oSubjects 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).
oSubjects with hepatic disease or clinically relevant evidence of it (i.e. values at screening or pre randomization of more than 3 x ULN for aspartate aminotransferase [AST], alanine aminotransferase [ALT] or alkaline phosphatase or values of more than 1.5 x ULN for bilirubin). Subjects with high bilirubin associated with Gilberts syndrome will not be excluded.
oSubjects who have a history of malignancy.
oSubjects with cardiovascular disease within the previous 6 months prior to screening (including, but not limited to, myocardial infarction, stroke, peripheral vascular disease, ischemic changes at resting ECG).
oSubjects with severe and uncontrolled hypertension (blood pressure above 160/100 mmHg).
oSubjects with a history of unhealed diabetic ulcer.
oSubjects with hypo or hyperthyroidism.
12.Subjects who have been hospitalized for any psychiatric illness in the past year, or are diagnosed with major depression.
13.Subjects with any other clinically significant laboratory abnormality at screening.
14.Has a clinical condition or receiving therapy that, in the opinion of the Investigator, would make the subjects unsuitable for study.
15.Subjects who have received in the 3 months prior to screening, any systemic glucocorticoid treatment.
16.Use of antiobesity treatments within 3 months prior to screening.