A Phase 1, Double-blind, Randomized, Placebo-controlled, Single- and Multiple-dose Escalating Study

Study Overview
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Brief Summary
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This will be a randomized, double-blind, placebo-controlled, single- and multiple SC dose escalating study conducted in 2 parts.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Placebo
* Drug: PB 718


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to comprehend and willing to sign an ICF and to abide by the study restrictions. Males or females, of any race, between 18 and 55 years of age, inclusive. 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. 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: 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). 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. 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. History of multiple endocrine neoplasia type 2 or an abnormal thyroid function test (thyroid stimulating hormone, triiodothyronine, thyroxine) at Screening or Baseline. Fasting plasma glucose greater than ≥126 mg/dL at Baseline. Hemoglobin A1c value >6.5% History of chronic or acute pancreatitis, or amylase or lipase exceeding 2 × ULN at Screening or Baseline. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A1<br>PB-718 vs placebo | Drug: Placebo<br>* matching placebo<br>Drug: PB 718<br>* dose in the next group will be determined following a review of data from the previous group<br>|
| Experimental: Group A2<br>PB-718 vs placebo | Drug: Placebo<br>* matching placebo<br>Drug: PB 718<br>* dose in the next group will be determined following a review of data from the previous group<br>|
| Experimental: Group A3<br>PB-718 vs placebo | Drug: Placebo<br>* matching placebo<br>Drug: PB 718<br>* dose in the next group will be determined following a review of data from the previous group<br>|
| Experimental: Group A4<br>PB-718 vs placebo | Drug: Placebo<br>* matching placebo<br>Drug: PB 718<br>* dose in the next group will be determined following a review of data from the previous group<br>|
| Experimental: Group A5<br>PB-718 vs placebo | Drug: Placebo<br>* matching placebo<br>Drug: PB 718<br>* dose in the next group will be determined following a review of data from the previous group<br>|
| Experimental: Group A6<br>PB-718 vs placebo | Drug: Placebo<br>* matching placebo<br>Drug: PB 718<br>* dose in the next group will be determined following a review of data from the previous group<br>|
| Experimental: Group B1<br>PB-718 vs placebo | Drug: Placebo<br>* matching placebo<br>Drug: PB 718<br>* dose in the next group will be determined following a review of data from the previous group<br>|
| Experimental: Group B2<br>PB-718 vs placebo | Drug: Placebo<br>* matching placebo<br>Drug: PB 718<br>* dose in the next group will be determined following a review of data from the previous group<br>|
| Experimental: Group B3<br>PB-718 vs placebo | Drug: Placebo<br>* matching placebo<br>Drug: PB 718<br>* dose in the next group will be determined following a review of data from the previous group<br>|
| Experimental: Group B4<br>PB-718 vs placebo | Drug: Placebo<br>* matching placebo<br>Drug: PB 718<br>* dose in the next group will be determined following a review of data from the previous group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 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. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) profile | 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) | 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. | 
| Pharmacokinetic (PK) profile | Cmax (maximum observed plasma concentration) | 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. | 
| Pharmacokinetic (PK) profile | Tmax (time of the maximum observed plasma concentration) | 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. | 
| Pharmacokinetic (PK) profile | terminal disposition phase rate constant (λz) | 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. |