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

Phase 1

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: 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)

• Registration Number: NCT01236404
• Lead Sponsor: PhaseBio Pharmaceuticals Inc.

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11
• Study First Submitted: 2010-11-05
• Study First Submitted QC: 2010-11-05
• Study First Posted: 2010-11-08
• Primary Completion: 2011-11
• Study Completion: 2011-11
• Status Verified: 2013-05
• Disposition First Submitted: 2013-05-06
• Disposition First Submitted QC: 2013-05-13
• Last Update Submitted: 2013-05-13
• Disposition First Posted: 2013-05-21
• Last Update Posted: 2013-05-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PB1023 Injection	Single Subcutaneous Dose (Part A) of PB1023 or Placebo (0.9% NaCl)	Subcutaneous injection PB1023
PB1023 Injection	Multiple (Four Weekly) Subcutaneous Injections (Part B) of PB1023 or Placebo (0.9% NaCl)	Subcutaneous injection PB1023
Placebo (0.9% Sodium Chloride Injection)	Single Subcutaneous Dose (Part A) of PB1023 or Placebo (0.9% NaCl)	Subcutaneous Injection Placebo
Placebo (0.9% Sodium Chloride Injection)	Multiple (Four Weekly) Subcutaneous Injections (Part B) of PB1023 or Placebo (0.9% NaCl)	Subcutaneous Injection Placebo

Primary Outcome Measures

Name	Time	Method
Safety/Tolerability	Screening to Final Visit (up to approximately 10 weeks for SAD and 14 weeks for MAD)	Safety will be evaluated by analyses of incidence of adverse events of interest (possibly related to the class of drug) and other adverse events. Vital signs, ECGs and safety laboratory parameters will also be presented.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic Profile	SAD: Pre-dose, 1, 4, 8, and 12 hours post-dose and Day 1, 2, 3, 5, 7, 10, 14, 21 and 28. MAD: Pre-dose, 1, 4, 8, and 12 hours post-dose and Day 1, 2, 3, 5, pre-dose Days 7, 14 and 21 and at 1, 4, 8, and 12 hours post-dose and Day 22, 23, 26, 28, 35, 42,	To characterize the PK profile of PB1023 after single and multiple ascending doses of PB1023. The following parameters will be evaluated: t1/2, AUC(inf), AUC(0-t), Tmax, Cmax, Elimination Rate Constant, Clearance and Distribution.
Pharmacodynamic Response	Fasting plasma glucose collected the day before dosing and with PK samples, excluding day of dosing. SAD MMTT to occur on day 0 and 2, MAD MMTT to occur on Day 0 and 22 with continuous glucose monitoring on Day -8/-7 to Day 0 and on Day 21 to Day 28.	To assess the pharmacodynamic response of various single and multiple doses of PB1023 (daily fasting plasma glucose and serial glucose (and continuous monitoring as defined in time frame), c-peptide and insulin levels in response to a liquid mixed meal tolerance test (MMTT) pre and post dose) on subjects washed off their baseline oral antihyperglycemic agents.

Trial Locations

Locations (3)

Diablo Clinical Research; 🇺🇸 Walnut Creek, California, United States

Prism Research; 🇺🇸 Saint Paul, Minnesota, United States

Rainier Clinical Research Center, Inc.; 🇺🇸 Renton, Washington, United States