Healthy Subjects
Conditions
Brief summary
This will be a randomized, double-blind, placebo-controlled, single- and multiple SC dose escalating study conducted in 2 parts.
Detailed description
A Phase 1, double-blind, randomized, placebo-controlled, single and multiple-dose escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PB-718 following subcutaneous administration in healthy subjects.
Interventions
DRUGPlacebo
matching placebo
DRUGPB 718
dose in the next group will be determined following a review of data from the previous group
Sponsors
Covance
PegBio Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The Investigator and other members of staff involved with the study will remain blinded to the treatment randomization code during the assembly procedure. The placebo solution will be identical in appearance to the PB-718.
Intervention model description
In Part A, 48 subjects will be studied in 6 groups (Groups A1 to A6), with each group consisting of 8 subjects. In Part B, 32 subjects will be studied in 4 groups (Groups B1 to B4), with each group consisting of 8 subjects Following review of the safety, tolerability, and PK data, additional dose groups may be added to the study. Up to 3 further groups of 8 subjects (6 PB-718: 2 placebo) may be included in each of Parts A and B.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Able to comprehend and willing to sign an ICF and to abide by the study restrictions. 2. Males or females, of any race, between 18 and 55 years of age, inclusive. 3. Male subjects will weigh at least 50 kg, and female subjects will weigh at least 45 kg. Body mass index between 20.0 and 30.0 kg/m2 (Part A) or 25.0 to 50.0 kg/m2 (Part B), inclusive. 4. In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[eg, suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at Screening and Check-in/predose as assessed by the Investigator (or designee).
Exclusion criteria
1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular or other heart disease, gastrointestinal, urinary/prostatic, neurological, respiratory, endocrine, or psychiatric disorder, or glaucoma, as determined by the Investigator (or designee). 2. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 3. Liver disease or liver injury, as indicated by abnormal liver function tests (e.g. serum bilirubin, direct bilirubin, ALT, AST, γ-GT, or ALK exceeding the ULN) at Screening or Baseline which may be repeated for confirmation per the Investigators discretion at Screening and Check-in. 4. History of multiple endocrine neoplasia type 2 or an abnormal thyroid function test (thyroid stimulating hormone, triiodothyronine, thyroxine) at Screening or Baseline. 5. Fasting plasma glucose greater than ≥126 mg/dL at Baseline. 6. Hemoglobin A1c value \>6.5% 7. History of chronic or acute pancreatitis, or amylase or lipase exceeding 2 × ULN at Screening or Baseline. -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | From Group A1 until Group B4. The study duration for each subject in Part A will be approximately 8 weeks. The study duration for each subject in Part B will be approximately 11 weeks. | Incidence, causality, and severity of AE. The condition of each subject will be monitored from the time of signing the ICF to Final Discharge from the study. Subjects will be observed for any signs or symptoms and asked about their condition by open questioning, such as How have you been feeling since you were last asked?, at least once each day while resident at the study site and at each study visit. Subjects will also be encouraged to spontaneously report AEs occurring at any other time during the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) profile | From Group A1 until Group B4. The study duration for each subject in Part A will be approximately 8 weeks. The study duration for each subject in Part B will be approximately 11 weeks. | AUC (area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration) from time zero to the time of the last quantifiable concentration (AUC0-tlast) |
Countries
United States
Outcome results
None listed