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

• ClinicalTrials.gov Identifier: NCT03072407
• Recruitment Status: Completed
• First Posted: March 7, 2017
• Last Update Posted: April 20, 2018
• Sponsor: PegBio Co., Ltd.
• Information provided by (Responsible Party): PegBio Co., Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Type2 Diabetes Mellitus	Biological: PB-119 injection; Biological: PB-119 injection placebo	Phase 1

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: placebo-control , parallel
• Masking: Single (Participant)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 24, 2015
• Actual Primary Completion Date: November 2, 2016
• Actual Study Completion Date: November 15, 2016

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: PB-119 injection placebo; totally 8 subjects will have PB-119 injection placebo once per weekly for 4 weeks.	Biological: PB-119 injection placebo
Experimental: PB-119 injection 25ug; totally 8 subjects will have PB-119 injection 25 ug once per weekly for 4 weeks	Biological: PB-119 injection
Experimental: PB-119 injection 50ug; totally 8 subjects will have PB-119 injection 50 ug once per weekly for 4 weeks	Biological: PB-119 injection
Experimental: PB-119 injection 100ug; totally 8 subjects will have PB-119 injection 100 ug once per weekly for 4 weeks	Biological: PB-119 injection
Experimental: PB-119 injection 200ug; totally 8 subjects will have PB-119 injection 200 ug once per weekly for 4 weeks	Biological: PB-119 injection

Outcome Measures

Primary Outcome Measures :

1. the number of AEs and the finding from the physical examination, the abnormal lab results [ Time Frame: accessed up to 4 weeks ]
   include monitoring of AEs, vital signs (blood pressure, pulse rate, respiratory)

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Florida

Clinical Pharmacology of Miami, Inc.

Miami, Florida, United States, 33014

United States, New Jersey

Frontage Clinical Services. Inc.

Hackensack, New Jersey, United States, 07601

Sponsors and Collaborators

PegBio Co., Ltd.

Investigators

• Principal Investigator: Gregory Tracey, Dr.; Frontage Clinical Services, Inc.

More Information

• Responsible Party: PegBio Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03072407
• Other Study ID Numbers: CSP-PB119-US01-01
• First Posted: March 7, 2017
• Last Update Posted: April 20, 2018
• Last Verified: April 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases