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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Phase 1/2a, Randomized, Double-Blind Placebo-Controlled, Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Response of PB1023 Injection Following Single and Multiple Ascending Subcutaneous Doses in Adult Subjects With Type 2 Diabetes Mellitus (T2DM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01236404
• Other study ID #: PB1023-PT-CL-0001
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 5, 2010
• Last updated: May 13, 2013
• Start date: November 2010
• Est. completion date: November 2011

Study information

• Verified date: May 2013
• Source: PhaseBio Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

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

• Multiple (Four Weekly) Subcutaneous Injections (Part B) of PB1023 or Placebo (0.9% NaCl)
Once weekly injections for up to four weeks

Locations

Country	Name	City	State
United States	Rainier Clinical Research Center, Inc.	Renton	Washington
United States	Prism Research	Saint Paul	Minnesota
United States	Diablo Clinical Research	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
PhaseBio Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety/Tolerability	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.	Screening to Final Visit (up to approximately 10 weeks for SAD and 14 weeks for MAD)	Yes
Secondary	Pharmacokinetic Profile	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.	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,	No
Secondary	Pharmacodynamic Response	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.	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.	No