Type2 Diabetes Mellitus
Conditions
Brief 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.
Detailed description
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
Interventions
BIOLOGICALPB-119 injection
BIOLOGICALPB-119 injection placebo
Sponsors
PegBio Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
placebo-control , parallel
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the number of AEs and the finding from the physical examination, the abnormal lab results | accessed up to 4 weeks | include monitoring of AEs, vital signs (blood pressure, pulse rate, respiratory) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PB-119 blood plasma concentration | accessed up to 4 weeks | to collect PB-119 blood plasma concentration of the subjects who use PB-119 intervention |
| PB-119 antibody | accessed up to 4 weeks | the number of subjects who are with positive antibody results |
| Insulin sensitivity (SI) | accessed up to 4 weeks | be estimated from glucose and insulin concentration |
| Beta-cell Responsivity Index | accessed up to 4 weeks | be estimated from serum glucose and c-peptide concentrations |
| Disposition Index | accessed up to 4 weeks | be calculated for each individual subject as the product of SI and Φtotal |
Countries
United States
Outcome results
None listed