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

Type2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03072407
• Other study ID #: CSP-PB119-US01-01
• Status: Completed
• Phase: Phase 1
• First received: March 2, 2017
• Last updated: April 18, 2018
• Start date: November 24, 2015
• Est. completion date: November 15, 2016

Study information

• Verified date: April 2018
• Source: PegBio Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 15, 2016
• Est. primary completion date: November 2, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type2 Diabetes Mellitus

Intervention

Biological:
• PB-119 injection

• PB-119 injection placebo

Locations

Country	Name	City	State
United States	Frontage Clinical Services. Inc.	Hackensack	New Jersey
United States	Clinical Pharmacology of Miami, Inc.	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
PegBio Co., Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	PB-119 antibody	the number of subjects who are with positive antibody results	accessed up to 4 weeks
Secondary	Insulin sensitivity (SI)	be estimated from glucose and insulin concentration	accessed up to 4 weeks
Secondary	Beta-cell Responsivity Index	be estimated from serum glucose and c-peptide concentrations	accessed up to 4 weeks
Secondary	Disposition Index	be calculated for each individual subject as the product of SI and Ftotal	accessed up to 4 weeks