Phase 1/2a, Randomized, Double-Blind, Placebo-Controlled, Study to Assess Safety, Tolerability, PK and PD Response of PB1023 Injection Following Single and Multiple SQ Doses in Adults With Type 2 Diabetes Mellitus

PhaseBio Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Single Subcutaneous Dose (Part A) of PB1023 or Placebo (0.9% NaCl); Drug: Multiple (Four Weekly) Subcutaneous Injections (Part B) of PB1023 or Placebo (0.9% NaCl)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01236404

PB1023-PT-CL-0001

Details and patient eligibility

About

Primary objective:

To evaluate the safety and tolerability of single and multiple ascending doses of PB1023 administered as a subcutaneous (SC) injection in adult subjects with T2DM.

Secondary objectives:

1. To characterize the pharmacokinetic profile of PB1023 after single and multiple ascending doses of PB1023.
2. To assess the pharmacodynamic response of various single and multiple doses of PB1023 (daily fasting plasma glucose, and serial glucose, c-peptide and insulin levels in response to a liquid Mixed Meal Tolerance Test (MMTT).

Enrollment: 80 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males or post menopausal or surgically sterile females age 18-75 years of age inclusive.
• Diagnosed with T2DM for > or = 6 months with HbA1c > or = 6.0% but < or = 9.0% while taking stable doses of one oral antihyperglycemic agent but < or = 8.5% when taking two oral antihyperglycemic agents for up to a maximum of 3 months prior to screening.
• Fasting Plasma glucose between 115 mg/dL and 269 mg/dL.
• Fasting C-peptide of > or = 0.8 ng/mL.
• BMI < or = 40 kg/m2.
• Otherwise stable health except for T2DM.

Exclusion criteria

• Currently taking a non-oral antihyperglycemic agent.
• Have taken a PPARg agonist within 90 days of screening.
• Known allergy to an approved or investigational GLP-1 receptor analog/agonist.
• Unstable cardiovascular disease as defined in clinical protocol.
• History, symptoms or signs of pancreatitis or severe gastrointestinal disease.
• Personal or family history of medullary thyroid tumors history of Multiple Endocrine Neoplasia Syndrome Type 2.
• Poor glucose control as defined in clinical protocol.
• Clinically significant renal and/or hepatic dysfunction as defined in clinical protocol.
• Absolute requirement for corticosteroids or received systemic steroids within 90 days prior to PB1023 administration.
• Pregnant or lactating females.
• Known history or active alcohol or drug abuse within 12 months prior to screening.
• Positive for HIV, Hepatitis B surface antigen or Hepatitis C antibodies.
• Participating in any other study within 30 days prior to screening.
• Other medical or psychiatric condition which in the opinion of the investigator would place the subject at increased risk.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

PB1023 Injection

Experimental group

Description:

Subcutaneous injection PB1023

Treatment:

Drug: Multiple (Four Weekly) Subcutaneous Injections (Part B) of PB1023 or Placebo (0.9% NaCl)

Drug: Single Subcutaneous Dose (Part A) of PB1023 or Placebo (0.9% NaCl)

Placebo (0.9% Sodium Chloride Injection)

Placebo Comparator group

Description:

Subcutaneous Injection Placebo

Treatment:

Drug: Multiple (Four Weekly) Subcutaneous Injections (Part B) of PB1023 or Placebo (0.9% NaCl)

Drug: Single Subcutaneous Dose (Part A) of PB1023 or Placebo (0.9% NaCl)