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

PhaseBio Pharmaceuticals Inc.6 sites in 1 country37 target enrollmentOctober 2015

ConditionsType 2 Diabetes Mellitus

InterventionsPE0139 Injection Placebo Injection

DrugsPE0139 Injection Placebo Injection

Overview

Phase: Phase 2
Intervention: PE0139 Injection
Conditions: Type 2 Diabetes Mellitus
Sponsor: PhaseBio Pharmaceuticals Inc.
Enrollment: 37
Locations: 6
Primary Endpoint: 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).
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Detailed Description

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.

Registry

clinicaltrials.gov

Start Date

October 2015

End Date

November 2016

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

PhaseBio Pharmaceuticals Inc.

Responsible Party

Sponsor

Eligibility Criteria

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;

Arms & Interventions

PE0139 Injection

PE0139 Subcutaneous Injection - 6 weekly doses

Intervention: PE0139 Injection

Placebo Injection

Placebo Subcutaneous Injection - 6 weekly doses

Intervention: Placebo Injection

Outcomes

Primary Outcomes

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).

Time Frame: 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).

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.

Secondary Outcomes

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).)
Pharmacodynamic (PD) Profile - Change from baseline in average glucose by CGM(PD response measured by continuous glucose monitoring (CGM) (baseline collected ≥7 days pre-dose daily after dose 3 for 4 weeks))
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 - Clearance (CL/F), uncorrected for bioavailability(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).)
Pharmacodynamic (PD) Profile - Change from baseline in fasting plasma glucose(PD response measured as fasting plasma glucose (FPG) (daily by subject up to day 21 and Days -60, between days -10 and -7, 0, 1-7, 14, 21, 28, 35, 36-49 and 63 at CRU))
Reported hypoglycemic events (% of subjects experiencing severe and non-severe hypoglycemic events)(All scheduled and unscheduled visits (Days -60 to 63))
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).)
Fructosamine changes(Measured at pre-dose and 7 days after last dose)
Required dose adjustment to background therapy(All scheduled and unscheduled visits (Days -60 to 63))
Pharmacokinetic (PK) profile - Elimination half-life (t1/2)(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 - Volume of Distribution (Vz/F), uncorrected for bioavailability(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).)
Binding anti-drug antibodies to PE0139 and insulin (as needed). If positive, neutralizing activity will also be assessed.(Collected at Pre-dose, Days 7, 14, 21, 28, 35, 42, 49, 63 and 91.)