MAD Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PB-119 to Subjects With T2DM

Study Overview
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Brief Summary
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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
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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

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Group, MAD Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PB-119 to Subjects With T2DM

Conditions
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Type2 Diabetes Mellitus

Intervention / Treatment
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* Biological: PB-119 injection
* Biological: PB-119 injection placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). In good general health as determined by the investigator at screening evaluation Male and/or female subjects between the ages of 18 and 70 years, inclusive; Are capable of giving informed consent and complying with study procedures; Body Mass Index (BMI) of approximately 22 to 40 kg/m2; Fasting C-peptide test result must be >0.4 nmol/L; HbA1c ≥6.5 % and ≤12%; Female subjects must have a negative urine pregnancy test result prior to enrollment. Nonsmoker, Willing and able to adhere to study restrictions and to be confined at the clinical research center. Exclusion Criteria: Subjects with a personal or family history of medullary thyroid carcinoma (MTC) or in subjects with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); Screening fasting blood glucose ≤100 or ≥270 mg/dL Type 1 diabetes mellitus, or latent autoimmune diabetes in adults; diabetic neuropathy, retinopathy or nephropathy; Previous treatment with an approved or investigational GLP-1 mimetic; Patients treated with any investigational drugs within 6 weeks of screening; Subjects with pancreatitis; Clinically significant gastrointestinal disorder History or symptoms of clinically significant cardiovascular disease, particularly coronary artery disease, arrhythmias, atrial tachycardia, Uncontrolled hypertension at screening; History of clinically significant central nervous system disease including: transient ischemic attack, stroke, seizure disorder, depression, History of liver disease History of clinically significant renal disease Uncontrolled severe dyslipidemia; Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody; A hospital admission or major surgery within 30 days prior to screening; A history of prescription drug abuse, or illicit drug use within 6 months prior to screening; A history of alcohol abuse according to medical history within 6 months prior to screening; A positive screen for alcohol, or drugs of abuse; An unwillingness or inability to comply with food and beverage restrictions during study participation; Use of prescription or over-the-counter (OTC) medications, and herbal An 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: placebo-control , parallel
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: PB-119 injection placebo<br>totally 8 subjects will have PB-119 injection placebo once per weekly for 4 weeks. | Biological: PB-119 injection placebo<br> <br> |
| Experimental: PB-119 injection 25ug<br>totally 8 subjects will have PB-119 injection 25 ug once per weekly for 4 weeks | Biological: PB-119 injection<br> <br> |
| Experimental: PB-119 injection 50ug<br>totally 8 subjects will have PB-119 injection 50 ug once per weekly for 4 weeks | Biological: PB-119 injection<br> <br> |
| Experimental: PB-119 injection 100ug<br>totally 8 subjects will have PB-119 injection 100 ug once per weekly for 4 weeks | Biological: PB-119 injection<br> <br> |
| Experimental: PB-119 injection 200ug<br>totally 8 subjects will have PB-119 injection 200 ug once per weekly for 4 weeks | Biological: PB-119 injection<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the number of AEs and the finding from the physical examination, the abnormal lab results | include monitoring of AEs, vital signs (blood pressure, pulse rate, respiratory) | accessed up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PB-119 blood plasma concentration | to collect PB-119 blood plasma concentration of the subjects who use PB-119 intervention | accessed up to 4 weeks | 
| PB-119 antibody | the number of subjects who are with positive antibody results | accessed up to 4 weeks | 
| Insulin sensitivity (SI) | be estimated from glucose and insulin concentration | accessed up to 4 weeks | 
| Beta-cell Responsivity Index | be estimated from serum glucose and c-peptide concentrations | accessed up to 4 weeks | 
| Disposition Index | be calculated for each individual subject as the product of SI and Φtotal | accessed up to 4 weeks |