Study to Assess the Safety, Tolerability, PK and PD Response of PE0139 Injection in Adult Subjects With T2DM

Phase 2a Multicenter, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Response of PE0139 Injection in Adult Subjects With Type 2 Diabetes Mellitus

This study is a randomized, double-blind (Investigator and study subject), placebo controlled multiple dose sequential ascending dose study that will enroll up to 47 male and female subjects with type 2 diabetes mellitus (T2DM) in up to four cohorts.

This study is a randomized, double-blind (Investigator and study subject), placebo controlled multiple dose sequential ascending dose study that will enroll up to 47 male and female subjects with T2DM in up to four cohorts; (6 active/2 placebo subjects in cohort 1, and up to 9 active/4 placebo in each subsequent cohort).

This study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamic response of PE0139 in the presence of existing stable non-insulin antidiabetic background therapy. Subjects will return weekly for a total of 6 doses of study drug.

Study remains active, not recruiting as subjects who received active study drug will be followed for secondary outcome measures.

Inclusion Criteria:

• Willing and able to sign a written informed consent and follow all study-related procedures;
• Male subjects and female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 30 days after their last dose of study drug;
• Body mass index ≥ 18 kg/m2 and ≤ 45 kg/m2;
• Diagnosed with T2DM with HbA1c of ≥ 7.5% and <11.0% and who is currently taking a non-insulin antidiabetic therapy at stable dose(s) for 3 months prior to screening;
• Willing and able to comply with all study procedures including wearing a continuous glucose monitoring device and performance of frequent self-monitored blood glucose profiles according to the protocol;
• Minimum 7-day average daily glucose of 154 mg/dL (based on CGM) at baseline evaluation;
• Willing to refrain from taking acetaminophen (paracetamol) containing products (e.g., Tylenol®) 24 hours prior to the placement of the CGM device and throughout the time period when the CGM device is worn;
• Live and work in an area with reliable Verizon cellular service for transmission of glucose data required for use of the Telcare Glucose Monitoring System.

Exclusion Criteria:

• Clinical diagnosis of Type 1 diabetes;
• Currently taking or have routinely taken, within 6 months prior to screening, a long or short-acting insulin;
• Self-reported significant change in weight defined as either a loss or gain ≥ 10% during the three month period prior to screening or between screening and randomization;
• Known allergy to, or serious adverse effect caused by an approved, or investigational insulin product or any of its components;
• Currently taking any of the following medications: thiazide or furosemide diuretics, beta-blockers, estrogens or other hormonal replacement therapy, or other chronic medications with known adverse effects on glucose tolerance levels unless the subject has been on stable doses of such agents for at least 2 months prior to screening and have no planned changes in concomitant medication usage during the study period;
• Self-reported history of severe hypoglycemia or hypoglycemic unawareness, as judged by the Investigator;
• Self-reported history of acute complications secondary to diabetes within the last 6 months prior to screening or signs or symptoms of clinically significant diabetes related complications prior to screening;
• Malignant disease defined as: Self-reported history of malignant melanoma or breast cancer; Self-reported history of other types of cancer (excludes basal/squamous cell carcinoma or cervical carcinoma if treated and condition not currently active) within the last 5 years prior to screening;
• Unstable cardiovascular disease defined as one or more of the following: Self-reported history of stroke, transient ischemic attack, or myocardial infarction within 6 months prior to screening; Self-reported history of or currently have NYHA Class III-IV heart failure prior to screening; Self-reported history of unstable angina within 3 months prior to screening; Uncontrolled/sustained hypertension; Self-reported history of clinically significant ECG abnormalities or evidence of clinically significant ECG abnormalities;
• Clinically significant renal and/or hepatic dysfunction noted on safety labs;
• Absolute requirement for corticosteroids or have routinely received systemic steroids within 12 months prior to randomization or use of inhaled corticosteroids within 1 month prior to randomization. A single short course treatment of systemic steroids to treat an acute infection will not exclude the subject if taken more than 3 months from screening;
• Pregnant or lactating female subjects;
• Known history of alcohol abuse or use of illicit drugs within 1 year prior to screening, and/or who test positive for alcohol and illicit drugs prior to randomization. Note: A subject will be considered in violation of the study if they test positive prior to any planned dosing and will be discontinued from the study;
• Positive screening for human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C virus antibodies at screening;
• Previously received PE0139;
• Participating in any other study and have received any other investigational medication or device within 30 days prior to screening or are taking part in a non-medication study which, in the opinion of the Investigator, would interfere with the outcome of the study;
• Other medical or psychiatric condition which, in the opinion of the Investigator, would place the subject at increased risk or would preclude obtaining voluntary consent or would confound the secondary objectives of the study.