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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
PhaseBio Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01236404
First received: November 5, 2010
Last updated: May 13, 2013
Last verified: May 2013
  Purpose

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 Intervention 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 Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by PhaseBio Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Safety/Tolerability [ Time Frame: Screening to Final Visit (up to approximately 10 weeks for SAD and 14 weeks for MAD) ] [ Designated as safety issue: Yes ]
    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:
  • 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, ] [ Designated as safety issue: No ]
    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 [ 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. ] [ Designated as safety issue: No ]
    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.


Enrollment: 80
Study Start Date: November 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01236404

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

No publications provided

Responsible Party: PhaseBio Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01236404     History of Changes
Other Study ID Numbers: PB1023-PT-CL-0001
Study First Received: November 5, 2010
Last Updated: May 13, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 23, 2014