Pharmacokinetic Profile of Two Formulations of PB1023 Following Single Subcutaneous Injection in Subjects With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
PhaseBio Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01427257
First received: August 29, 2011
Last updated: September 28, 2012
Last verified: September 2012
  Purpose

Primary objective:

To compare the pharmacokinetic profile of PB1023 after a single dose administered by subcutaneous injection of two formulations (concentrations).

Secondary objectives:

To evaluate the safety and tolerability of two formulations of PB1023 Injection administered as a subcutaneous injection in adult subjects with T2DM.

To evaluate the impact on the pharmacokinetic profile of PB1023 after a single 90 mg dose of formulation B (100 mg/mL) administered cold at 2 to 8°C by subcutaneous injection.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Single Dose PB1023
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Open-Label Two-Way Cross Over Study to Assess the Pharmacokinetic Profile of Two Formulations of PB1023 Injection Following a Single Dose Administered By Subcutaneous Injection 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:
  • Pharmacokinetics [ Time Frame: For each dosing period: Pre-dose, 1, 4, 8, 12 hours, 1, 2, 3, 4, 7 and 10 days post-dose ] [ Designated as safety issue: No ]
    The pharmacokinetic profile of two formulations of PB1023 will be compared. The following parameters will be evaluated: t1/2, AUC(inf), AUC(0-t), Tmax, Cmax, Elimination Rate Constant, Clearance and Distribution.


Secondary Outcome Measures:
  • Safety/Tolerability [ Time Frame: 42 Days ] [ 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.


Enrollment: 10
Study Start Date: February 2012
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: PB1023 Formulation A Drug: Single Dose PB1023
Single Dose PB1023 Formulation A
Active Comparator: PB1023 Formulation B Drug: Single Dose PB1023
Single Dose PB1023 Formulation B
Active Comparator: PB1023 Formulation B (2-8C) Drug: Single Dose PB1023
Single Dose PB1023 Formulation B

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Willing and able to sign a written informed consent and follow all study related procedures.
  • Males or post menopausal or surgically sterile females age 18 - 75 years of age inclusive.
  • Diagnosed with T2DM for ≥ 6 months.
  • HbA1c of ≥ 6.0% if diet and exercise controlled, or ≥5.8% if taking one or more glucose lowering agents
  • Weight ≥ 45 kg and BMI ≤ 40 kg/m2
  • In otherwise stable health except for T2DM (no clinically significant laboratory abnormalities, vital signs, ECG findings or clinically significant underlying disease that would put the subject at risk for participation in the study).
  • Receiving stable doses of concomitant medications for 30 days prior to dosing.
  • Criteria for Participation in Period 3 only: Received PB1023 Injection at 50 mg/mL and 100 mg/mL during Period 1 or 2 of the study and had adequate pharmacokinetic samples collected for evaluation of their pharmacokinetic profile.

Exclusion Criteria:

  • Currently taking Byetta® or Victoza®.
  • Previously received PB1023 Injection other than under this study protocol.
  • Known allergy or serious adverse effect to an approved or investigational GLP-1 receptor analog/agonist.
  • Unstable cardiovascular disease defined as:

    • History of stroke, transient ischemic attack, or myocardial infarction within 6 months prior to the Screening visit.
    • Screening (duplicate supine reading) BP ≥ 160 mmHg (systolic) or ≥ 100 mmHg (diastolic).
    • Mean triplicate 12-lead ECG demonstrating QT interval (corrected) (QTc) > 450 msec in males and > 470 msec in females at the Screening visit, or a history or evidence of long QT syndrome.
  • Based on contraindications/warnings identified with other GLP-1 receptor agonists, subjects will be excluded if they have:

    • History, symptoms or signs of pancreatitis or severe gastrointestinal disease (i.e., gastroparesis)
    • Personal or family history of medullary thyroid tumors or history of Multiple Endocrine Neoplasia Syndrome Type 2. Note: Abnormal serum calcitonin at screening will exclude the subject from participation.
  • Clinically significant renal and/or hepatic dysfunction at screening as indicated by the following:

    • eGFR as calculated by MDRD of < 60 mL/min
    • Urine dipstick protein > 2+ (100 mg/dL) or urine protein 2+ and a Urine Protein/Creatinine ratio > 1.0 (> 1000 mg/g)
    • Alanine aminotransferase (ALT) > 2 x ULN
    • Aspartate aminotransferase (AST) > 2 x ULN
    • Serum bilirubin ≥ 1.6 mg/dL
  • Pregnant or lactating females
  • Known history of or active alcohol or drug abuse within 12 months prior to Screening or positive alcohol and/or drug screen.
  • Positive for Human Immunodeficiency Virus (HIV) antibodies, Hepatitis B surface antigen (HBsAg) or Hepatitis C Virus (HCV) antibodies.
  • Participating in any other study and have received any other investigational drug or device within 30 days prior to the Screening visit or are taking part in a non-drug study which in the opinion of the Investigator would interfere with the outcome of the study.
  • Other medical (i.e., acute or chronic illness) or psychiatric condition which in the opinion of the Investigator would place the subject at increased risk, confound the primary study endpoint, or would preclude obtaining voluntary consent.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01427257

Locations
United States, Minnesota
Prism Research
Saint Paul, Minnesota, United States, 55114
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: NCT01427257     History of Changes
Other Study ID Numbers: PB1023-PT-CL-0002
Study First Received: August 29, 2011
Last Updated: September 28, 2012
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 17, 2014