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

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

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.

Study Overview

• Status: Completed
• Conditions: Type2 Diabetes Mellitus
• Intervention / Treatment: Biological: PB-119 injection; Biological: PB-119 injection placebo

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami, Inc.
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Frontage Clinical Services. Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

5

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: PegBio Co., Ltd.
• Investigators: Principal Investigator: Gregory Tracey, Dr., Frontage Clinical Services, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 24, 2015
• Primary Completion (ACTUAL): November 2, 2016
• Study Completion (ACTUAL): November 15, 2016

Study Registration Dates

• First Submitted: March 2, 2017
• First Submitted That Met QC Criteria: March 6, 2017
• First Posted (ACTUAL): March 7, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 20, 2018
• Last Update Submitted That Met QC Criteria: April 18, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: CSP-PB119-US01-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No