Trial Outcomes & Findings for Avexitide Safety and Efficacy to Treat Acquired Hyperinsulinemic Hypoglycemia (NCT NCT04652479)

NCT ID: NCT04652479

Last Updated: 2023-06-09

Results Overview

Level 2 hypoglycemia events (ADA, \<54 mg/dL) as measured by CGM and defined as the number of events captured by CGM with glucose measures \<54 mg/dL during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 25 participants
• Primary outcome timeframe: Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days)
• Results posted on: 2023-06-09

Participant Flow

25 participants entered a 14-day run-in (screening) period during which they wore the continuous glucose monitor (CGM). 17 participants who had at least 2 hypoglycemic events were randomized to a study arm.

Participant milestones

Measure	Run-in (All Participants) 14-day run-in period during which hypoglycemic events were recorded by CGM.	Avexitide 45 mg Twice Daily Then Avexitide 90 mg Once Daily Patients receive one of the two dosing regimens of avexitide for 14 days followed by the other dosing regimen of avextide for 14 days	Avexitide 90 mg Once Daily Then Avexitide 45 mg Twice Daily Patients receive one of the two dosing regimens of avexitide for 14 days followed by the other dosing regimen of avextide for 14 days
Run-in Period (14 Days) STARTED	25	0	0
Run-in Period (14 Days) COMPLETED	25	0	0
Run-in Period (14 Days) NOT COMPLETED	0	0	0
Treatment Period 1 (14 Days) STARTED	0	8	9
Treatment Period 1 (14 Days) COMPLETED	0	8	9
Treatment Period 1 (14 Days) NOT COMPLETED	0	0	0
Washout Period (2 Days) STARTED	0	8	9
Washout Period (2 Days) COMPLETED	0	8	9
Washout Period (2 Days) NOT COMPLETED	0	0	0
Treatment Period 2 (14 Days STARTED	0	8	9
Treatment Period 2 (14 Days Completed Both Interventions With no Major Protocol Deviations	0	8	8
Treatment Period 2 (14 Days COMPLETED	0	8	9
Treatment Period 2 (14 Days NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Avexitide Safety and Efficacy to Treat Acquired Hyperinsulinemic Hypoglycemia

Baseline characteristics by cohort

Measure	Avexitide 45 mg Twice Daily Then Avexitide 90 mg Once Daily n=8 Participants Patients receive one of the two dosing regimens of avexitide for 14 days followed by the other dosing regimen of avextide for 14 days	Avexitide 90 mg Once Daily Then Avexitide 45 mg Twice Daily n=8 Participants Patients receive one of the two dosing regimens of avexitide for 14 days followed by the other dosing regimen of avextide for 14 days	Total n=16 Participants Total of all reporting groups
Age, Continuous	48.1 years STANDARD_DEVIATION 15.2 • n=5 Participants	47.8 years STANDARD_DEVIATION 11.2 • n=7 Participants	47.9 years STANDARD_DEVIATION 12.8 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days)

Population: Participants with no major protocol deviations who were allocated to treatment.

Level 2 hypoglycemia events (ADA, <54 mg/dL) as measured by CGM and defined as the number of events captured by CGM with glucose measures <54 mg/dL during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days.

Outcome measures

Measure	Avexitide 45 mg Twice Daily n=16 Participants Patients receive avexitide 45 mg twice daily for 14 days	Avexitide 90 mg Once Daily n=16 Participants Patients receive avexitide 90 mg once daily for 14 days
Diurnal Level 2 Hypoglycemia Events (ADA, <54 mg/dL) as Measured by CGM in Patients With Severe Hyperinsulinemic Hypoglycemia (HH) Run-in period	5.2 events per 14 days Standard Deviation 3.52	5.2 events per 14 days Standard Deviation 3.52
Diurnal Level 2 Hypoglycemia Events (ADA, <54 mg/dL) as Measured by CGM in Patients With Severe Hyperinsulinemic Hypoglycemia (HH) Treatment period	2.7 events per 14 days Standard Deviation 2.15	2.1 events per 14 days Standard Deviation 2.99

SECONDARY outcome

Timeframe: Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days)

Population: Participants with no major protocol deviations who were allocated to treatment.

Distinct episodes of Level 2 hypoglycemia (SMBG glucose <54 mg/dL), divided by number of days for run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days.

Outcome measures

Measure	Avexitide 45 mg Twice Daily n=16 Participants Patients receive avexitide 45 mg twice daily for 14 days	Avexitide 90 mg Once Daily n=16 Participants Patients receive avexitide 90 mg once daily for 14 days
Rate of Level 2 Hypoglycemia (ADA, <54 mg/dL) as Measured by SMBG Run-in period	2.7 episodes per 14 days Standard Deviation 3.1	2.7 episodes per 14 days Standard Deviation 3.1
Rate of Level 2 Hypoglycemia (ADA, <54 mg/dL) as Measured by SMBG Treatment period	1.2 episodes per 14 days Standard Deviation 1.4	1.3 episodes per 14 days Standard Deviation 3.7

SECONDARY outcome

Timeframe: Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days)

Population: Participants with no major protocol deviations who were allocated to treatment.

Severe events during each treatment period characterized by altered mental and/or physical functioning that requires assistance from another person for recovery; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days. This would apply regardless of whether a patient actually received external assistance.

Outcome measures

Measure	Avexitide 45 mg Twice Daily n=16 Participants Patients receive avexitide 45 mg twice daily for 14 days	Avexitide 90 mg Once Daily n=16 Participants Patients receive avexitide 90 mg once daily for 14 days
Rate of Level 3 Hypoglycemia Run-in period	2.5 events per 14 days Standard Deviation 3.1	2.5 events per 14 days Standard Deviation 3.1
Rate of Level 3 Hypoglycemia Treatment period	0.8 events per 14 days Standard Deviation 1.2	0.9 events per 14 days Standard Deviation 2.9

SECONDARY outcome

Timeframe: Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days)

Population: Participants with no major protocol deviations who were allocated to treatment.

Percentage of time in level 2 hypoglycemia (<54mg/dL by CGM) during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days.

Outcome measures

Measure	Avexitide 45 mg Twice Daily n=16 Participants Patients receive avexitide 45 mg twice daily for 14 days	Avexitide 90 mg Once Daily n=16 Participants Patients receive avexitide 90 mg once daily for 14 days
Percent Time in Level 2 Hypoglycemia (<54 mg/dL) as Measured by CGM (Diurnal Time) Run-in period	1.50 percentage of time per 14 days Standard Deviation 1.32	1.50 percentage of time per 14 days Standard Deviation 1.32
Percent Time in Level 2 Hypoglycemia (<54 mg/dL) as Measured by CGM (Diurnal Time) Treatment period	0.96 percentage of time per 14 days Standard Deviation 0.74	0.48 percentage of time per 14 days Standard Deviation 0.82

SECONDARY outcome

Timeframe: Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days)

Population: Participants with no major protocol deviations who were allocated to treatment.

Percentage of time in level 1 hypoglycemia (<70mg/dL by CGM) during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days.

Outcome measures

Measure	Avexitide 45 mg Twice Daily n=16 Participants Patients receive avexitide 45 mg twice daily for 14 days	Avexitide 90 mg Once Daily n=16 Participants Patients receive avexitide 90 mg once daily for 14 days
Percent Time in Level 1 Hypoglycemia (<70 mg/dL) as Measured by CGM (Diurnal Time) Run-in period	4.20 percentage of time per 14 days Standard Deviation 2.75	4.20 percentage of time per 14 days Standard Deviation 2.75
Percent Time in Level 1 Hypoglycemia (<70 mg/dL) as Measured by CGM (Diurnal Time) Treatment period	2.86 percentage of time per 14 days Standard Deviation 1.54	1.96 percentage of time per 14 days Standard Deviation 1.63

SECONDARY outcome

Timeframe: 3 Hours Following Standardized Liquid Meal

Population: Data were not collected for this outcome

Change from Baseline in glycemia During Standardized Mixed Meal Consumption

Outcome measures

Outcome data not reported

Adverse Events

Run-in Period

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Avexitide 45 mg Twice Daily

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Avexitide 90 mg Once Daily

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Run-in Period n=25 participants at risk Adverse events collected during the run-in period	Avexitide 45 mg Twice Daily n=17 participants at risk Adverse events collected during the avexitide 45 mg twice daily treatment period	Avexitide 90 mg Once Daily n=17 participants at risk Adverse events collected during the avexitide 90 mg once daily treatment period
Skin and subcutaneous tissue disorders injection site bruising	0.00% 0/25 • 44 days	35.3% 6/17 • Number of events 6 • 44 days	47.1% 8/17 • Number of events 8 • 44 days
Gastrointestinal disorders loose stools	0.00% 0/25 • 44 days	29.4% 5/17 • Number of events 5 • 44 days	23.5% 4/17 • Number of events 4 • 44 days
Nervous system disorders headache	0.00% 0/25 • 44 days	11.8% 2/17 • Number of events 2 • 44 days	11.8% 2/17 • Number of events 2 • 44 days

Additional Information

Marilyn Tan, MD, FACE

Stanford University

Phone: (650) 721-1300

Email: mjtan@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place