Intravenous Exenatide (Byetta) During Surgery

NCT00882050 | Completed Phase 1 Results DMC

• 1 other identifier: 808104
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this project is to study if intravenous Exenatide is effective at maintaining normal blood glucose levels and preventing low blood glucose levels during surgery.

Conditions

Euglycemia; Hypoglycemia; Hyperglycemia

Outcome Measures

Primary Outcomes (1)

• The Primary Objective is to Determine the Ability of Intravenous Exenatide to: Maintain Intraoperative Euglycemia in Subjects With Initial Blood Glucose < 126 mg/dL in Surgical Subjects as Compared to Placebo,

  Logistic regression analysis will be utizlized to determine maintenance of euglycemia (yes v no) for our primary analysis. A standard area under the curve (AUC) analysis will be performed for each time point to map out drug deposition. Assuming a standard 2 compartment model, 10 subjects per group is sufficient to accurately predict mean AUC. Our primary analysis should provide ample statistical power.

  Baseline and 90 minutes after starting infusion;

Study Arms (3)

Exentatide 0.27 ng/kg/min

EXPERIMENTAL

Exenatide to be infused by intravenous method at 0.27 ng/kg/min (0.066 pmol/kg/min) over 3-6 hours. * Induction of anesthesia will be equal to Intubation time. Infusion will begin at this time point (+ or - 3 minutes). * Blood samples will be obtained prior to intubation and then 10 and 30 minutes after drug initiation and every 30 minutes (+ or - 2 minutes) thereafter until the infusion is stopped. The drug infusion will be stopped at extubation. Blood will then be sampled every 30 minutes (+ or - 2 minutes) post extubation for 2 hours, and once 24 hours after extubation. * Blood plasma levels will be collected (8-10 mls) for analysis of GLP-1, Glucose, Potassium, Insulin, Glucagon, Epinephrine, Norepinephrine, Cortisol, and free fatty acids (FFA).

Drug: Exenatide 0.27 ng/kg/min

Exentatide 0.41 ng/kg/min

EXPERIMENTAL

Experimental: IV Exenatide to be infused by intravenous method at 0.41 ng/kg/min (0.099 pmol/kg/min) over 3 to 6 hours. * Induction of anesthesia will be equal to Intubation time. Infusion will begin at this time point (+ or - 3 minutes). * Blood samples will be obtained prior to intubation and then 10 and 30 minutes after drug initiation and every 30 minutes (+ or - 2 minutes) thereafter until the infusion is stopped. The drug infusion will be stopped at extubation. Blood will then be sampled every 30 minutes (+ or - 2 minutes) post extubation for 2 hours, and once 24 hours after extubation. * Blood plasma levels will be collected (8-10 mls) for analysis of GLP-1, Glucose, Potassium, Insulin,Glucagon, Epinephrine, Norepinephrine, Cortisol, and free fatty acids (FFA).

Drug: Exenatide 0.41 ng/kg/min

Placebo IV NSS

PLACEBO COMPARATOR

Placebo of IV normal saline solution as comparator. * Induction of anesthesia will be equal to Intubation time. Infusion will begin at this time point (+ or - 3 minutes). * Blood samples will be obtained prior to intubation and then 10 and 30 minutes after drug initiation and every 30 minutes (+ or - 2 minutes) thereafter until the infusion is stopped. The drug infusion will be stopped at extubation. Blood will then be sampled every 30 minutes (+ or - 2 minutes) post extubation for 2 hours, and once 24 hours after extubation. * Blood plasma levels will be collected (8-10 mls) for analysis of GLP-1, Glucose, Potassium, Insulin, Glucagon, Epinephrine, Norepinephrine, Cortisol, and free fatty acids (FFA).

Drug: Placebo

Interventions

Exenatide 0.27 ng/kg/min DRUG

Exenatide to be infused intravenously at 0.27 ng/kg/min (0.066 pmol/kg/min) for a duration of 3 to 6 hours. * Induction of anesthesia will be equal to Intubation time. Infusion will begin at this time point (+ or - 3 minutes). * Blood samples will be obtained prior to intubation and then 10 and 30 minutes after drug initiation and every 30 minutes (+ or - 2 minutes) thereafter until the infusion is stopped. The drug infusion will be stopped at extubation. Blood will then be sampled every 30 minutes (+ or - 2 minutes) post extubation for 2 hours, and once 24 hours after extubation. * Blood plasma levels will be collected (8-10 mls) for analysis of GLP-1, Glucose, Potassium, Insulin, Glucagon, Epinephrine, Norepinephrine, Cortisol, and free fatty acids (FFA).

Also known as: Byetta

Exentatide 0.27 ng/kg/min

Exenatide 0.41 ng/kg/min DRUG

Exenatide to be infused intravenously 0.41 ng/kg/min (0.099 pmol/kg/min) for a duration of 3 to 6 hours Induction of anesthesia will be equal to Intubation time. Infusion will begin at this time point (+ or - 3 minutes). * Blood samples will be obtained prior to intubation and then 10 and 30 minutes after drug initiation and every 30 minutes (+ or - 2 minutes) thereafter until the infusion is stopped. The drug infusion will be stopped at extubation. Blood will then be sampled every 30 minutes (+ or - 2 minutes) post extubation for 2 hours, and once 24 hours after extubation. * Blood plasma levels will be collected (8-10 mls) for analysis of GLP-1, Glucose, Potassium, Insulin, Glucagon, Epinephrine, Norepinephrine, Cortisol, and free fatty acids (FFA).

Also known as: Byetta

Exentatide 0.41 ng/kg/min

Placebo DRUG

Intravenous Placebo of NSS infused at same rate as drug comparator. Induction of anesthesia will be equal to Intubation time. Infusion will begin at this time point (+ or - 3 minutes). * Blood samples will be obtained prior to intubation and then 10 and 30 minutes after drug initiation and every 30 minutes (+ or - 2 minutes) thereafter until the infusion is stopped. The drug infusion will be stopped at extubation. Blood will then be sampled every 30 minutes (+ or - 2 minutes) post extubation for 2 hours, and once 24 hours after extubation. * Blood plasma levels will be collected (8-10 mls) for analysis of GLP-1, Glucose, Potassium, Insulin, Glucagon, Epinephrine, Norepinephrine, Cortisol, and free fatty acids (FFA).

Also known as: Normal Saline Solution

Placebo IV NSS

Eligibility Criteria

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

You may qualify if:

• Age (\>18 years)
• Weight of \> 50 kg and \< 150 kg
• Ability to provide informed consent
• Elective surgery including:
• Cardiac surgery to include elective CABG with or without single or multivalve repair or replacement and/or single or multivalve repair/replacement requiring CPB and sternotomy (to include subjects who are undergoing first time or redo cardiac surgery)
• Abdominal aortic aneurysm repair
• Carotid endarterectomy
• Esophagectomy
• Cystectomy
• Nephrectomy
• If female, subject must be non-lactating, and, if of childbearing potential, must have a negative urine pregnancy test within 24 hours prior to receiving study drug

You may not qualify if:

• Age (\<18 years)
• Inability to provide informed consent
• History or risk of pancreatitis (e.g. ethanol abuse, gall stones)
• Receipt of an investigational drug or device with 30 days prior to surgery
• Use of any concomitant medication listed above on the day of surgery
• Known allergy to Exenatide, fentanyl, midazolam, isoflurane, propofol, heparin or neuromuscular blockers
• Known substance abuse
• Surgical procedure other than:
• Cardiac surgery to include elective CABG with or without single or multivalve repair or replacement and/or single or multivalve repair/ replacement requiring CPB and sternotomy (to include subjects who are undergoing first time or redo cardiac surgery)
• Abdominal aortic aneurysm repair
• Carotid endarterectomy
• Esophagectomy
• Cystectomy
• Nephrectomy
• Insulin dependent diabetes mellitis

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Amylin Pharmaceuticals, LLC.: collaborator
• Eli Lilly and Company: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Hypoglycemia; Hyperglycemia

Interventions

Exenatide; Saline Solution

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Change in PI during the trial led to intermittent study activitity and a delay in enrollment which prolonged the study and final data entry.

Results Point of Contact

• Title: Kim Lacy, RN BSN
• Organization: University of Pennsylvania

kim.lacy@uphs.upenn.edu

215-893-7234

Study Officials

• Benjamin A. Kohl, MD

  University of Pennsylvania

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2009
• First Posted: April 16, 2009
• Study Start: March 1, 2009
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: January 21, 2022
• Results First Posted: January 21, 2022

Record last verified: 2021-12

Locations

US (1)