Pharmacokinetic Profile of Two Formulations of PB1023 Following Single Subcutaneous Injection in Subjects With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Primary objective: To compare the pharmacokinetic profile of PB1023 after a single dose administered by subcutaneous injection of two formulations (concentrations). Secondary objectives: To evaluate the safety and tolerability of two formulations of PB1023 Injection administered as a subcutaneous injection in adult subjects with T2DM. To evaluate the impact on the pharmacokinetic profile of PB1023 after a single 90 mg dose of formulation B (100 mg/mL) administered cold at 2 to 8°C by subcutaneous injection.

Official Title
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Phase 1 Open-Label Two-Way Cross Over Study to Assess the Pharmacokinetic Profile of Two Formulations of PB1023 Injection Following a Single Dose Administered By Subcutaneous Injection in Adult Subjects With Type 2 Diabetes Mellitus (T2DM)

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Single Dose PB1023
* Drug: Single Dose PB1023
* Drug: Single Dose PB1023


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to sign a written informed consent and follow all study related procedures. Males or post menopausal or surgically sterile females age 18 - 75 years of age inclusive. Diagnosed with T2DM for ≥ 6 months. HbA1c of ≥ 6.0% if diet and exercise controlled, or ≥5.8% if taking one or more glucose lowering agents Weight ≥ 45 kg and BMI ≤ 40 kg/m2 In otherwise stable health except for T2DM (no clinically significant laboratory abnormalities, vital signs, ECG findings or clinically significant underlying disease that would put the subject at risk for participation in the study). Receiving stable doses of concomitant medications for 30 days prior to dosing. Criteria for Participation in Period 3 only: Received PB1023 Injection at 50 mg/mL and 100 mg/mL during Period 1 or 2 of the study and had adequate pharmacokinetic samples collected for evaluation of their pharmacokinetic profile. Exclusion Criteria: Currently taking Byetta® or Victoza®. Previously received PB1023 Injection other than under this study protocol. Known allergy or serious adverse effect to an approved or investigational GLP-1 receptor analog/agonist. Unstable cardiovascular disease defined as: History of stroke, transient ischemic attack, or myocardial infarction within 6 months prior to the Screening visit. Screening (duplicate supine reading) BP ≥ 160 mmHg (systolic) or ≥ 100 mmHg (diastolic). Mean triplicate 12-lead ECG demonstrating QT interval (corrected) (QTc) > 450 msec in males and > 470 msec in females at the Screening visit, or a history or evidence of long QT syndrome. Based on contraindications/warnings identified with other GLP-1 receptor agonists, subjects will be excluded if they have: History, symptoms or signs of pancreatitis or severe gastrointestinal disease (i.e., gastroparesis) Personal or family history of medullary thyroid tumors or history of Multiple Endocrine Neoplasia Syndrome Type 2. Note: Abnormal serum calcitonin at screening will exclude the subject from participation. Clinically significant renal and/or hepatic dysfunction at screening as indicated by the following: eGFR as calculated by MDRD of < 60 mL/min Urine dipstick protein > 2+ (100 mg/dL) or urine protein 2+ and a Urine Protein/Creatinine ratio > 1.0 (> 1000 mg/g) Alanine aminotransferase (ALT) > 2 x ULN Aspartate aminotransferase (AST) > 2 x ULN Serum bilirubin ≥ 1.6 mg/dL Pregnant or lactating females Known history of or active alcohol or drug abuse within 12 months prior to Screening or positive alcohol and/or drug screen. Positive for Human Immunodeficiency Virus (HIV) antibodies, Hepatitis B surface antigen (HBsAg) or Hepatitis C Virus (HCV) antibodies. Participating in any other study and have received any other investigational drug or device within 30 days prior to the Screening visit or are taking part in a non-drug study which in the opinion of the Investigator would interfere with the outcome of the study. Other medical (i.e., acute or chronic illness) or psychiatric condition which in the opinion of the Investigator would place the subject at increased risk, confound the primary study endpoint, or would preclude obtaining voluntary consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PB1023 Formulation A<br> | Drug: Single Dose PB1023<br>* Single Dose PB1023 Formulation A<br>|
| Active Comparator: PB1023 Formulation B<br> | Drug: Single Dose PB1023<br>* Single Dose PB1023 Formulation B<br>|
| Active Comparator: PB1023 Formulation B (2-8C)<br> | Drug: Single Dose PB1023<br>* Single Dose PB1023 Formulation B<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics | The pharmacokinetic profile of two formulations of PB1023 will be compared. The following parameters will be evaluated: t1/2, AUC(inf), AUC(0-t), Tmax, Cmax, Elimination Rate Constant, Clearance and Distribution. | For each dosing period: Pre-dose, 1, 4, 8, 12 hours, 1, 2, 3, 4, 7 and 10 days post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety/Tolerability | Safety will be evaluated by analyses of incidence of adverse events of interest (possibly related to the class of drug) and other adverse events. Vital signs, ECGs and safety laboratory parameters will also be presented. | 42 Days |