Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia

NCT00835328 | Terminated Phase 1 Results

• 1 other identifier: 2008-10-6256
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of this study is to evaluate the effect of Exendin (9-39) on glucose requirements to maintain euglycemia in pediatric patients with congenital hyperinsulinism (CHI) who have failed medical therapy. The secondary aims are to determine the therapeutic plasma levels, plasma half-life and pharmacokinetics of Exendin (9-39) during a 9-hour intravenous infusion.

Conditions

Congenital Hyperinsulinism

Keywords

Congenital Hyperinsulinism; Hyperinsulinism; Hypoglycemia; KATP channel; Metabolic Diseases; Pancreatic Disease; Glucose Metabolism Disorders; Infant, Newborn, Diseases

Outcome Measures

Primary Outcomes (2)

• Mean Glucose Infusion Rate (GIR)

  To assess the effect of Exendin (9-39) on glucose infusion rate, glucose infusion rate (GIR) over the last 2 hours of the treatment period was calculated by adding the total amount of intravenous glucose (mg) received over 2 hours divided by the weight (kg) and by time (120 min) during infusion of Exendin (9-39) and normal saline vehicle.

  Up to 9 hours after the initiation of infusion

• To Determine the Pharmacokinetics of Exendin (9-39)

  The following PK variables of interest include AUC0-∞, AUC0-t, maximal concentration (Cmax), time to maximal concentration (Tmax), concentration at end of infusion (Ceoi), steady state volume of distribution (Vss), clearance (CL) and half-life (t1/2) of Exendin (9-39). These will be derived through both non-compartmental and model-based methods.

  Up to 12 hours after the initiation of infusion

Secondary Outcomes (4)

• Safety and Tolerability of Exendin (9-39)

  Up to 24 hours post-infusion

• Mean Plasma Insulin

  Up to 9 hours after the initiation of infusion

• Mean Plasma Glucose

  Up to 9 hours after the initiation of infusion

• Mean Betahydroxybutyrate Levels

  Up to 12 hours after the initiation of infusion

Study Arms (4)

Exendin (9-39) 0.02 mg/kg/hr

EXPERIMENTAL

Cohort 1: Participants will be administered 0.02 mg/kg/hr of Exendin (9-39) and vehicle (normal saline), via continuous intravenous infusion, over 9 hours on two separate days in random order, with 3 hours of follow-up after the last dose is administered or until blood glucose is \< 70 mg/dL (whichever comes first). Glucose infusion rates (GIR) will be titrated three hours prior to infusions to keep blood glucose in the range of 70-90 mg/dL. During both infusions, blood glucose will be measured every 30 minutes.

Drug: Exendin (9-39); Drug: Vehicle

Exendin (9-39) 0.04 mg/kg/hr

EXPERIMENTAL

Cohort 2: Participants will be administered 0.04 mg/kg/hr of Exendin (9-39) and vehicle (normal saline), via continuous intravenous infusion, over 9 hours on two separate days in random order, with 3 hours of follow-up after the last dose is administered or until blood glucose is \< 70 mg/dL (whichever comes first). Glucose infusion rates (GIR) will be titrated three hours prior to infusions to keep blood glucose in the range of 70-90 mg/dL. During both infusions, blood glucose will be measured every 30 minutes.

Drug: Exendin (9-39); Drug: Vehicle

Exendin (9-39) 0.10 mg/kg/hr

EXPERIMENTAL

Cohort 3: Participants will be administered 0.10 mg/kg/hr of Exendin (9-39) and vehicle (normal saline), via continuous intravenous infusion, over 6 hours on two separate days in random order, with 3 hours of follow-up after the last dose is administered or until blood glucose is \< 70 mg/dL (whichever comes first). Glucose infusion rates (GIR) will be titrated three hours prior to infusions to keep blood glucose in the range of 70-90 mg/dL. During both infusions, blood glucose will be measured every 30 minutes.

Drug: Exendin (9-39); Drug: Vehicle

Exendin (9-39) 0.20 mg/kg/hr

EXPERIMENTAL

Cohort 4: Participants will be administered 0.20 mg/kg/hr of Exendin (9-39) and vehicle (normal saline), via continuous intravenous infusion, over 9 hours on two separate days in random order, with 3 hours of follow-up after the last dose is administered or until blood glucose is \< 70 mg/dL (whichever comes first). Glucose infusion rates (GIR) will be titrated three hours prior to infusions to keep blood glucose in the range of 70-90 mg/dL. During both infusions, blood glucose will be measured every 30 minutes.

Drug: Exendin (9-39); Drug: Vehicle

Interventions

Exendin (9-39) DRUG

A short-term intravenous infusion of the investigational drug, Exendin (9-39), will be administered over up to 9 hours.

Exendin (9-39) 0.02 mg/kg/hr; Exendin (9-39) 0.04 mg/kg/hr; Exendin (9-39) 0.10 mg/kg/hr; Exendin (9-39) 0.20 mg/kg/hr

Vehicle DRUG

A short-term intravenous infusion of normal saline (0.9% NaCl), or the vehicle, will be administered over up to 9 hours.

Also known as: Placebo

Exendin (9-39) 0.02 mg/kg/hr; Exendin (9-39) 0.04 mg/kg/hr; Exendin (9-39) 0.10 mg/kg/hr; Exendin (9-39) 0.20 mg/kg/hr

Eligibility Criteria

• Age: Up to 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Confirmed clinical diagnosis of congenital hyperinsulinism
• Infants less than 12 months of age at study enrollment
• Failure to respond to treatment with diazoxide

You may not qualify if:

• Evidence of a medical condition that might alter results, including kidney failure, severe liver dysfunction, severe respiratory or cardiac failure
• Treatment with medications that may affect glucose metabolism at the time of initiation of study procedures, including:
• Treatment with glucagon 4 hours prior to infusion (T=0)
• Treatment with octreotide 24 hours prior to infusion (T=0)
• Treatment with diazoxide 72 hours prior to infusion (T=0)
• Suspected Beckwith-Wiedemann syndrome or other syndromic forms of congenital hyperinsulinism.

Sponsors & Collaborators

• Diva De Leon: lead

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Congenital Hyperinsulinism; Hyperinsulinism; Hypoglycemia; Metabolic Diseases; Pancreatic Diseases; Glucose Metabolism Disorders; Infant, Newborn, Diseases

Interventions

exendin (9-39)

Condition Hierarchy (Ancestors)

Digestive System Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases

Limitations and Caveats

The trial was terminated after 14 participants enrolled in the study. No data is available for any outcome measures.

Results Point of Contact

• Title: Diva D. Deleon, MD,MSCE
• Organization: The Children's Hospital of Philadelphia

deleon@email.chop.edu

215-590-3420

Study Officials

• Diva D De Leon, MD MSCE

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Pediatrics, Children's Hospital of Philadelphia

Model Details: This is a two-period, two-treatment cross-over clinical study with a dose-escalation component. Each subject, in random order, will receive an intravenous (IV) infusion of Exendin (9-39) and normal saline vehicle for up to 9 hours on two separate days.

Study Record Dates

• First Submitted: February 2, 2009
• First Posted: February 3, 2009
• Study Start: August 26, 2009
• Primary Completion: January 28, 2017
• Study Completion: January 28, 2017
• Last Updated: June 1, 2020
• Results First Posted: May 14, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)