mad study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of pb-119 to subjects with t2dm

Conditions: Type2 Diabetes Mellitus

Summary: this was a phase 1, randomized, double-blind, placebo-controlled, sequential parallel group, mad study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of four once-weekly subcutaneous doses of pb-119 to subjects with t2dm.

dose levels of 25 µg, 50 µg, 100 µg and 200 µg with a dosing regimen of once weekly for 4 consecutive weeks will be evaluated

Eligibility criteria:
inclusion criteria: 1. patients in whom t2dm has been diagnosed for at least 3 months prior to screening and have not been taking any treatment but have made lifestyle modifications (i.e., diet and exercise) for at least 4 weeks or are taking metformin (with no change in the treatment including dose over the past 2 months). 2. in good general health as determined by the investigator at screening evaluation 3. male and/or female subjects between the ages of 18 and 70 years, inclusive; 4. are capable of giving informed consent and complying with study procedures; 5. body mass index (bmi) of approximately 22 to 40 kg/m2; 6. fasting c-peptide test result must be \>0.4 nmol/l; 7. hba1c ≥6.5 % and ≤12%; 8. female subjects must have a negative urine pregnancy test result prior to enrollment. 9. nonsmoker, 10. willing and able to adhere to study restrictions and to be confined at the clinical research center. exclusion criteria: 1. subjects with a personal or family history of medullary thyroid carcinoma (mtc) or in subjects with multiple endocrine neoplasia syndrome type 2 (men 2); 2. screening fasting blood glucose ≤100 or ≥270 mg/dl 3. type 1 diabetes mellitus, or latent autoimmune diabetes in adults; diabetic neuropathy, retinopathy or nephropathy; 4. previous treatment with an approved or investigational glp-1 mimetic; 5. patients treated with any investigational drugs within 6 weeks of screening; 6. subjects with pancreatitis; 7. clinically significant gastrointestinal disorder 8. history or symptoms of clinically significant cardiovascular disease, particularly coronary artery disease, arrhythmias, atrial tachycardia, 9. uncontrolled hypertension at screening; 10. history of clinically significant central nervous system disease including: transient ischemic attack, stroke, seizure disorder, depression, 11. history of liver disease 12. history of clinically significant renal disease 13. uncontrolled severe dyslipidemia; 14. positive blood screen for human immunodeficiency virus (hiv), hepatitis b surface antigen (hbsag), or hepatitis c antibody; 15. a hospital admission or major surgery within 30 days prior to screening; 16. a history of prescription drug abuse, or illicit drug use within 6 months prior to screening; 17. a history of alcohol abuse according to medical history within 6 months prior to screening; 18. a positive screen for alcohol, or drugs of abuse; 19. an unwillingness or inability to comply with food and beverage restrictions during study participation; 20. use of prescription or over-the-counter (otc) medications, and herbal an 21. unwillingness of male participants to use appropriate contraceptive measures if engaging in sexual intercourse with a female partner of childbearing potential. appropriate measures include use of a condom and spermicide and, for female partners, use of an intrauterine device (iud), diaphragm with spermicide, oral contraceptives, injectable progesterone, progesterone subdermal implants, or a tubal ligation. sexual intercourse with pregnant or lactating women is prohibited