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

NCT02581657 | Completed Phase 2 FDA Drug

• 1 other identifier: PE0139-PT-CL-0002
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability (as assessed by incidence and severity of adverse events (AEs), hypoglycemia and changes from baseline in vital signs, ECGs and safety laboratory parameters).

  To evaluate the safety and tolerability (as assessed by incidence and severity of AEs, hypoglycemia and changes from baseline in vital signs, ECGs and safety laboratory parameters) of multiple ascending doses of PE0139 administered as once weekly injection for 6 weeks in adults with T2DM.

  AEs and hypoglycemia (Day -60 to 63), Vital signs (Days -60, -10, 0, 7, 14, 21, 28, 35, 42, 49 and 63), safety laboratory parameters (-60, -10, 14, 28, 42, 49 (as needed), and 63) ECGs (-60, -10, 14, 28, 42, 49 (as needed) and 63).

Secondary Outcomes (14)

• Pharmacokinetic (PK) profile - Area under the curve over the dosing interval (AUC (0-t))

  PK measured for Dose 1 (pre-dose, 1, 3, 6 hours post-dose, daily for 6 days), Doses 2-5 given on days 7, 14, 21 and 28, respectively, (pre-dose) and Dose 6 (pre-dose, 1, 3 and 6 hours post dose, daily for 10 days and 14 days post-dose).

• Pharmacokinetic (PK) profile - Area under the curve concentration-time profile from 0 to Tmax [AUC (0-tmax)] and from Tmax to t [AUC(tmax-t]

  PK measured for Dose 1 (pre-dose, 1, 3, 6 hours post-dose, daily for 6 days), Doses 2-5 given on days 7, 14, 21 and 28, respectively, (pre-dose) and Dose 6 (pre-dose, 1, 3 and 6 hours post dose, daily for 10 days and 14 days post-dose).

• Pharmacokinetic (PK) profile - Maximum serum concentration (Cmax)

  PK measured for Dose 1 (pre-dose, 1, 3, 6 hours post-dose, daily for 6 days), Doses 2-5 given on days 7, 14, 21 and 28, respectively, (pre-dose) and Dose 6 (pre-dose, 1, 3 and 6 hours post dose, daily for 10 days and 14 days post-dose).

• Pharmacokinetic (PK) profile - Time to Cmax (Tmax)

  PK measured for Dose 1 (pre-dose, 1, 3, 6 hours post-dose, daily for 6 days), Doses 2-5 given on days 7, 14, 21 and 28, respectively, (pre-dose) and Dose 6 (pre-dose, 1, 3 and 6 hours post dose, daily for 10 days and 14 days post-dose).

• Pharmacokinetic (PK) profile - Elimination Rate Constant (Lamda z)

  PK measured for Dose 1 (pre-dose, 1, 3, 6 hours post-dose, daily for 6 days), Doses 2-5 given on days 7, 14, 21 and 28, respectively, (pre-dose) and Dose 6 (pre-dose, 1, 3 and 6 hours post dose, daily for 10 days and 14 days post-dose).

Study Arms (2)

PE0139 Injection

EXPERIMENTAL

PE0139 Subcutaneous Injection - 6 weekly doses

Drug: PE0139 Injection

Placebo Injection

PLACEBO COMPARATOR

Placebo Subcutaneous Injection - 6 weekly doses

Drug: Placebo Injection

Interventions

PE0139 Injection DRUG

PE0139 Injection

PE0139 Injection

Placebo Injection DRUG

Placebo Injection

Placebo Injection

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• PhaseBio Pharmaceuticals Inc.: lead

Study Sites (6)

Pinnacle Research Group, LLC

Anniston, Alabama, 36207, United States

Location

National Research Institute

Huntington Park, California, 90255, United States

Location

Meridien Research

Bradenton, Florida, 34208, United States

Location

Indago Research and Health Center, Inc.

Hialeah, Florida, 33012, United States

Location

New Orleans Center for Clinical Research

New Orleans, Louisiana, 70119, United States

Location

Rainier Clinical Research

Renton, Washington, 98057, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2015
• First Posted: October 21, 2015
• Study Start: October 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: April 10, 2018

Record last verified: 2018-04

Locations

US (6)