Trial Outcomes & Findings for Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia (NCT NCT00835328)
NCT ID: NCT00835328
Last Updated: 2020-06-01
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
14 participants
Primary outcome timeframe
Up to 9 hours after the initiation of infusion
Results posted on
2020-06-01
Participant Flow
Participants were recruited based on a confirmed clinical diagnosis of congenital hyperinsulinism at 1 academic medical center between August 2009 and October 2019. The first participant was enrolled on August 26, 2008 and the last participant was enrolled in January 25, 2017.
Of the 14 enrolled participants, 13 met inclusion criteria and were randomized to treatment.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Cohort 1: Dose Level 1
STARTED
|
5
|
0
|
0
|
0
|
|
Cohort 1: Dose Level 1
COMPLETED
|
5
|
0
|
0
|
0
|
|
Cohort 1: Dose Level 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Cohort 2: Dose Level 2
STARTED
|
0
|
2
|
0
|
0
|
|
Cohort 2: Dose Level 2
COMPLETED
|
0
|
2
|
0
|
0
|
|
Cohort 2: Dose Level 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Cohort 3: Dose Level 3
STARTED
|
0
|
0
|
2
|
0
|
|
Cohort 3: Dose Level 3
COMPLETED
|
0
|
0
|
2
|
0
|
|
Cohort 3: Dose Level 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Cohort 4: Dose Level 4
STARTED
|
0
|
0
|
0
|
4
|
|
Cohort 4: Dose Level 4
COMPLETED
|
0
|
0
|
0
|
4
|
|
Cohort 4: Dose Level 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia
Baseline characteristics by cohort
| Measure |
Exendin (9-39) 0.02 mg/kg/hr
n=5 Participants
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).
|
Exendin (9-39) 0.04 mg/kg/hr
n=2 Participants
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).
|
Exendin (9-39) 0.10 mg/kg/hr
n=2 Participants
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).
|
Exendin (9-39) 0.20 mg/kg/hr
n=4 Participants
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).
|
Total
n=13 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
5 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=31 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
10 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
11 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
01 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: Up to 9 hours after the initiation of infusionPopulation: Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle. The trial was terminated after 14 participants enrolled in the study. No data is available for any outcome measures.
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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Up to 12 hours after the initiation of infusionPopulation: Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle. The trial was terminated after 14 participants enrolled in the study. No data is available for any outcome measures.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 24 hours post-infusionPopulation: Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle. The trial was terminated after 14 participants enrolled in the study. No data is available for any outcome measures.
Number of participants with adverse events as a measure of safety and tolerability \[evaluated by the result of laboratory safety tests (hematology, chemistry, urinalysis), vital signs, physical examinations, and 12-lead ECG\]
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 9 hours after the initiation of infusionPopulation: Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle. The trial was terminated after 14 participants enrolled in the study. No data is available for any outcome measures.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 9 hours after the initiation of infusionPopulation: Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle. The trial was terminated after 14 participants enrolled in the study. No data is available for any outcome measures.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 12 hours after the initiation of infusionPopulation: Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle. The trial was terminated after 14 participants enrolled in the study. No data is available for any outcome measures.
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.
Outcome measures
Outcome data not reported
Adverse Events
Exendin (9-39) 0.02 mg/kg/hr
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Exendin (9-39) 0.04 mg/kg/hr
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Exendin (9-39) 0.10 mg/kg/hr
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Exendin (9-39) 0.20 mg/kg/hr
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Vehicle
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Exendin (9-39) 0.02 mg/kg/hr
n=5 participants at risk；n=4 participants at risk
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).
|
Exendin (9-39) 0.04 mg/kg/hr
n=2 participants at risk
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).
|
Exendin (9-39) 0.10 mg/kg/hr
n=2 participants at risk
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).
|
Exendin (9-39) 0.20 mg/kg/hr
n=4 participants at risk
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).
|
Vehicle
n=13 participants at risk
All participants will be administered normal saline vehicle via continuous intravenous infusion.
|
|---|---|---|---|---|---|
|
Endocrine disorders
Hypoglycemia
|
20.0%
1/5 • Number of events 1 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
100.0%
2/2 • Number of events 2 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
50.0%
1/2 • Number of events 1 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
75.0%
3/4 • Number of events 3 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
61.5%
8/13 • Number of events 8 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
|
Gastrointestinal disorders
Emesis
|
0.00%
0/5 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
0.00%
0/2 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
50.0%
1/2 • Number of events 1 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
25.0%
1/4 • Number of events 1 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
15.4%
2/13 • Number of events 2 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
|
Endocrine disorders
Hyperglycemia
|
0.00%
0/5 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
0.00%
0/2 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
50.0%
1/2 • Number of events 1 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
0.00%
0/4 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
0.00%
0/13 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
|
Investigations
Abormal Lab Value - AST
|
0.00%
0/5 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
0.00%
0/2 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
0.00%
0/2 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
25.0%
1/4 • Number of events 1 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
0.00%
0/13 • Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.
Safety population = all participants who received any dose of the investigational product. Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle.
|
Additional Information
Diva D. Deleon, MD,MSCE
The Children's Hospital of Philadelphia
Phone: 215-590-3420
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place