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

NCT01427257 | Completed Phase 1 DMC

• 1 other identifier: PB1023-PT-CL-0002
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics

  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.

  For each dosing period: Pre-dose, 1, 4, 8, 12 hours, 1, 2, 3, 4, 7 and 10 days post-dose

Secondary Outcomes (1)

• Safety/Tolerability

  42 Days

Study Arms (3)

PB1023 Formulation A

ACTIVE COMPARATOR

Drug: Single Dose PB1023

PB1023 Formulation B

ACTIVE COMPARATOR

Drug: Single Dose PB1023

PB1023 Formulation B (2-8C)

ACTIVE COMPARATOR

Drug: Single Dose PB1023

Interventions

Single Dose PB1023 DRUG

Single Dose PB1023 Formulation A

PB1023 Formulation A

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• PhaseBio Pharmaceuticals Inc.: lead

Study Sites (1)

Prism Research

Saint Paul, Minnesota, 55114, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

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

Study Officials

• Mark Matson, M.D.

  Prism Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2011
• First Posted: September 1, 2011
• Study Start: February 1, 2012
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: October 1, 2012

Record last verified: 2012-09

Locations

US (1)