Clinical trial NCT03072407: MAD Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PB-119 to Subjects With T2DM
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type2 Diabetes Mellitus
Lead sponsor: PegBio Co., Ltd.
Sponsor class: OTHER
First posted: 2017-03-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: placebo-control , parallel
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: the number of AEs and the finding from the physical examination, the abnormal lab results
timeFrame: accessed up to 4 weeks
Secondary outcomes:
measure: PB-119 blood plasma concentration
timeFrame: accessed up to 4 weeks
measure: PB-119 antibody
timeFrame: accessed up to 4 weeks
measure: Insulin sensitivity (SI)
timeFrame: accessed up to 4 weeks
measure: Beta-cell Responsivity Index
timeFrame: accessed up to 4 weeks
measure: Disposition Index
timeFrame: accessed up to 4 weeks
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami, Inc.
state: Florida
city: Hackensack
country: United States
facility: Frontage Clinical Services. Inc.
state: New Jersey
Study officials:
affiliation: Frontage Clinical Services, Inc.
name: Gregory Tracey, Dr.
role: PRINCIPAL_INVESTIGATOR
References: