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

NCT01236404 | Completed Phase 1 DMC

• 1 other identifier: PB1023-PT-CL-0001
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

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. 1.To characterize the pharmacokinetic profile of PB1023 after single and multiple ascending doses of PB1023.
2. 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).

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (2)

• 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,

• 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.

Study Arms (2)

PB1023 Injection

EXPERIMENTAL

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)

Placebo (0.9% Sodium Chloride Injection)

PLACEBO COMPARATOR

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)

Interventions

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

PB1023 Injection; Placebo (0.9% Sodium Chloride Injection)

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

Once weekly injections for up to four weeks

PB1023 Injection; Placebo (0.9% Sodium Chloride Injection)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PhaseBio Pharmaceuticals Inc.: lead

Study Sites (3)

Diablo Clinical Research

Walnut Creek, California, 94598, United States

Location

Prism Research

Saint Paul, Minnesota, 55114, United States

Location

Rainier Clinical Research Center, Inc.

Renton, Washington, 98057, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Injections, Subcutaneous

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Injections; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Mark Matson, M.D.

  Prism Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2010
• First Posted: November 8, 2010
• Study Start: November 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: May 21, 2013

Record last verified: 2013-05

Locations

US (3)