Trial · Interventional

TerminatedPhase 1/2Results postedRegistry data

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

NCTNCT00835328Other id2008-10-6256

Open at ClinicalTrials.govAsk about this trial

This trial was stopped early.

Reason given at the registry: Study stopped prematurely to test a new formulation of Exendin (9-39)

Results were posted for this trial.

This trial does not test a peptide that PepBank tracks.

Measures Glucagon, does not give it. It appears in the eligibility rules.

Overview

Status: Terminated
Phase: Phase 1/2
Enrollment: 14 participants (actual)
Sponsor: Diva De Leon · Other
Design: Randomized · Open label (no masking)
Countries: 1 country
United States
Start: 26 Aug 2009
Primary completion: 28 Jan 2017
Completion: 28 Jan 2017
First posted: 3 Feb 2009 (estimated)
Last update posted: 1 Jun 2020
Conditions: Congenital Hyperinsulinism

Timeline

1 trial · 1 stopped early · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

20102012201420162018

Ph 1/2
Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia
NCT00835328
26 Aug 2009 to 28 Jan 2017
Terminated
Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

Exendin (9-39)Drug
VehicleDrug

Arms4

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

Primary outcomes2

Outcomes the sponsor listed as primary.

Mean Glucose Infusion Rate (GIR)
Time frame · Up to 9 hours after the initiation of infusion
Registry description
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.
To Determine the Pharmacokinetics of Exendin (9-39)
Time frame · Up to 12 hours after the initiation of infusion
Registry description
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.

Secondary outcomes(4)

Safety and Tolerability of Exendin (9-39)
Time frame · Up to 24 hours post-infusion
Registry description
Number of participants with adverse events as a measure of safety and tolerability \[evaluated by the result of laboratory safety tests (hematology, chemistry, urinalysis), vital signs, physical examinations, and 12-lead ECG\]
Mean Plasma Insulin
Time frame · Up to 9 hours after the initiation of infusion
Registry description
To assess the effect of Exendin (9-39) on plasma insulin levels, samples were collected at various time points during the infusion \[Exendin (9-39) or vehicle\] including: at the start of the infusion (T=0) and at 1, 5, and 9 hours post initiation of the infusion.
Mean Plasma Glucose
Time frame · Up to 9 hours after the initiation of infusion
Registry description
To assess the effect of Exendin (9-39) on plasma glucose levels, samples were collected at various time points during the infusion \[Exendin (9-39) or vehicle\] including: at the start of the infusion (T=0) and at 1, 5, and 9 hours post initiation of the infusion.
Mean Betahydroxybutyrate Levels
Time frame · Up to 12 hours after the initiation of infusion
Registry description
To assess the effect of Exendin (9-39) on mean betahydroxybutyrate levels, samples were collected at various time points during the infusion \[Exendin (9-39) or vehicle\] including: at the start of the infusion (T=0) and hourly up to 12-hours post initiation of the infusion.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcome· Up to 9 hours after the initiation of infusion

Mean Glucose Infusion Rate (GIR)

Group	Value
Exendin (9-39) 0.02 mg/kg/hr	not posted
Exendin (9-39) 0.04 mg/kg/hr	not posted
Exendin (9-39) 0.10 mg/kg/hr	not posted
Exendin (9-39) 0.20 mg/kg/hr	not posted
Vehicle	not posted

Primary outcome· Up to 12 hours after the initiation of infusion

To Determine the Pharmacokinetics of Exendin (9-39)

Group	Value
Exendin (9-39) 0.02 mg/kg/hr	not posted
Exendin (9-39) 0.04 mg/kg/hr	not posted
Exendin (9-39) 0.10 mg/kg/hr	not posted
Exendin (9-39) 0.20 mg/kg/hr	not posted
Vehicle	not posted

Secondary and other outcome results(4)

Secondary outcome· Up to 24 hours post-infusion

Safety and Tolerability of Exendin (9-39)

Group	Value
Exendin (9-39) 0.02 mg/kg/hr	not posted
Exendin (9-39) 0.04 mg/kg/hr	not posted
Exendin (9-39) 0.10 mg/kg/hr	not posted
Exendin (9-39) 0.20 mg/kg/hr	not posted
Vehicle	not posted

Secondary outcome· Up to 9 hours after the initiation of infusion

Mean Plasma Insulin

Group	Value
Exendin (9-39) 0.02 mg/kg/hr	not posted
Exendin (9-39) 0.04 mg/kg/hr	not posted
Exendin (9-39) 0.10 mg/kg/hr	not posted
Exendin (9-39) 0.20 mg/kg/hr	not posted
Vehicle	not posted

Secondary outcome· Up to 9 hours after the initiation of infusion

Mean Plasma Glucose

Group	Value
Exendin (9-39) 0.02 mg/kg/hr	not posted
Exendin (9-39) 0.04 mg/kg/hr	not posted
Exendin (9-39) 0.10 mg/kg/hr	not posted
Exendin (9-39) 0.20 mg/kg/hr	not posted
Vehicle	not posted

Secondary outcome· Up to 12 hours after the initiation of infusion

Mean Betahydroxybutyrate Levels

Group	Value
Exendin (9-39) 0.02 mg/kg/hr	not posted
Exendin (9-39) 0.04 mg/kg/hr	not posted
Exendin (9-39) 0.10 mg/kg/hr	not posted
Exendin (9-39) 0.20 mg/kg/hr	not posted
Vehicle	not posted

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Exendin (9-39) 0.02 mg/kg/hrCohort 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).	0 / 5	0 / 4	1 / 5
Exendin (9-39) 0.04 mg/kg/hrCohort 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).	0 / 2	0 / 2	2 / 2
Exendin (9-39) 0.10 mg/kg/hrCohort 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).	0 / 2	0 / 2	2 / 2
Exendin (9-39) 0.20 mg/kg/hrCohort 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).	0 / 4	0 / 4	4 / 4
VehicleAll participants will be administered normal saline vehicle via continuous intravenous infusion.	0 / 13	0 / 13	10 / 13

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: All
Age: up to 12 Months
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

Inclusion Criteria: 1. Confirmed clinical diagnosis of congenital hyperinsulinism 2. Infants less than 12 months of age at study enrollment 3. Failure to respond to treatment with diazoxide Exclusion Criteria: 1. Evidence of a medical condition that might alter results, including kidney failure, severe liver dysfunction, severe respiratory or cardiac failure 2. Treatment with medications that may affect glucose metabolism at the time of initiation of study procedures, including: 1. Treatment with glucagon 4 hours prior to infusion (T=0) 2. Treatment with octreotide 24 hours prior to infusion (T=0) 3. Treatment with diazoxide 72 hours prior to infusion (T=0) 3. Suspected Beckwith-Wiedemann syndrome or other syndromic forms of congenital hyperinsulinism.

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