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

• ClinicalTrials.gov Identifier: NCT01236404
• Recruitment Status: Completed
• First Posted: November 8, 2010
• Last Update Posted: May 21, 2013
• Sponsor: PhaseBio Pharmaceuticals Inc.
• Information provided by (Responsible Party): PhaseBio Pharmaceuticals Inc.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	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)	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Study Start Date: November 2010
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: November 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: PB1023 Injection; Subcutaneous injection PB1023	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); Once weekly injections for up to four weeks
Placebo Comparator: Placebo (0.9% Sodium Chloride Injection); Subcutaneous Injection Placebo	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); Once weekly injections for up to four weeks

Outcome Measures

Primary Outcome Measures :

1. Safety/Tolerability [ Time Frame: 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 :

1. Pharmacokinetic Profile [ Time Frame: 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.
2. Pharmacodynamic Response [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

Diablo Clinical Research

Walnut Creek, California, United States, 94598

United States, Minnesota

Prism Research

Saint Paul, Minnesota, United States, 55114

United States, Washington

Rainier Clinical Research Center, Inc.

Renton, Washington, United States, 98057

Sponsors and Collaborators

PhaseBio Pharmaceuticals Inc.

Investigators

• Principal Investigator: Mark Matson, M.D.; Prism Research

More Information

• Responsible Party: PhaseBio Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT01236404
• Other Study ID Numbers: PB1023-PT-CL-0001
• First Posted: November 8, 2010
• Last Update Posted: May 21, 2013
• Last Verified: May 2013

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases