Phase 2b Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group Study to Assess the PD Response and Safety of Three Dose Levels of (PB1023) Injection Following 20 Weeks of Weekly SC Dosing in Adults With T2DM

PhaseBio Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Metformin; Drug: Placebo (0.9% Sodium Chloride); Drug: Sulfonylurea; Drug: 50 mg PB1023; Drug: Victoza®; Drug: 70 mg PB1023; Other: Diet and Exercise; Drug: 100 mg PB1023; Drug: Metformin and Sulfonylurea

Study type: Interventional

Funder types: Industry

Identifiers

NCT01658501

PB1023-PT-CL-0004

Details and patient eligibility

About

Primary objective:

The primary objective of this study is to define the dose response of Glymera as measured as the change from baseline in hemoglobin A1c (HbA1c) following 20 weeks of once-weekly dosing.

Secondary objectives:

The secondary objectives are to:

• Describe incidence, severity, and duration of reported gastrointestinal side effects of Glymera compared to active comparator;
• Compare change from baseline in HbA1c following 20 weeks of dosing compared to placebo and active comparator;
• Compare change from baseline in fasting plasma glucose (FPG) following 20 weeks of dosing compared to placebo and active comparator;
• Describe the frequencies of adverse events in the treatment groups; and
• Describe the above endpoints for the following subgroups of subjects according to baseline type 2 diabetes mellitus (T2DM) therapy: diet and exercise only, metformin only, sulfonylurea only, or metformin and sulfonylurea combination therapy.

Enrollment: 593 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male and female subjects 18 to 75 years of age, inclusive;
• Body mass index ≤45 kg/m2;
• Diagnosed with T2DM with HbA1c of ≥7.0% and ≤11.0% and treated with diet and exercise alone, or with stable doses of metformin alone, sulfonylurea alone or metformin and sulfonylurea.

Exclusion criteria

• Currently taking or have taken within the last 6 months non-oral antihyperglycemic agents (eg, insulin, Byetta®, Bydureon®, or Victoza). Short-term use of insulin within this period will not be cause for exclusion if insulin was used during the treatment of an acute intercurrent illness;
• Known allergy to or serious adverse effect caused by an approved or investigational glucagon-like peptide-1 (GLP-1) receptor analog/agonist;
• Unstable cardiovascular disease;
• History of weight loss surgery or other gastrointestinal surgical procedures that could possibly interfere with the mechanism of action of GLP-1 receptor agonists;
• 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 (ie, gastroparesis) or Personal or family history of medullary thyroid tumors or history of Multiple Endocrine Neoplasia Syndrome Type 2;
• Clinically significant renal and/or hepatic dysfunction;
• Pregnant or lactating female subjects.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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593 participants in 7 patient groups, including a placebo group

Diet and Exercise

Experimental group

Description:

Diet and exercise only.

Treatment:

Drug: 100 mg PB1023

Drug: 70 mg PB1023

Drug: Victoza®

Drug: 50 mg PB1023

Drug: Placebo (0.9% Sodium Chloride)

Metformin

Experimental group

Description:

Metformin only

Treatment:

Drug: 100 mg PB1023

Drug: 70 mg PB1023

Drug: Victoza®

Drug: 50 mg PB1023

Drug: Placebo (0.9% Sodium Chloride)

Sulfonylurea

Experimental group

Description:

Sulfonylurea only

Treatment:

Drug: 100 mg PB1023

Drug: 70 mg PB1023

Drug: Victoza®

Drug: 50 mg PB1023

Drug: Placebo (0.9% Sodium Chloride)

Metformin and Sulfonylurea

Experimental group

Description:

Metformin and Sulfonylurea combination therapy

Treatment:

Drug: 100 mg PB1023

Drug: 70 mg PB1023

Drug: Victoza®

Drug: 50 mg PB1023

Drug: Placebo (0.9% Sodium Chloride)

PB1023

Experimental group

Description:

PB1023 weekly SC injection

Treatment:

Drug: Metformin and Sulfonylurea

Drug: 100 mg PB1023

Other: Diet and Exercise

Drug: 70 mg PB1023

Drug: Sulfonylurea

Drug: 50 mg PB1023

Drug: Metformin

Placebo Comparator

Placebo Comparator group

Description:

Placebo (0.9% Sodium Chloride) weekly SC injection

Treatment:

Drug: Metformin and Sulfonylurea

Other: Diet and Exercise

Drug: Sulfonylurea

Drug: Metformin

Drug: Placebo (0.9% Sodium Chloride)

Active Comparator

Active Comparator group

Description:

Active Comparator (Victoza) daily SC injection

Treatment:

Drug: Metformin and Sulfonylurea

Other: Diet and Exercise

Drug: Victoza®

Drug: Sulfonylurea

Drug: Metformin