Trial Outcomes & Findings for Evaluating the Benefits of Physiologic Insulin Delivery (NCT NCT04416737)

Last Updated: 2024-10-01

Results Overview

For each injection site we will assess the peak concentration of glucagon at time of the first induced hypoglycemic nadir. Analysis includes reporting groups for each type of injection, and upper and lower peritoneal injections combined (Injection- All Peritoneal). Participants must have achieved induced hypoglycemia to be evaluable for the primary outcome.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max

Results posted on

2024-10-01

Participant Flow

Participant milestones

Participant milestones
Measure	Upper Peritoneal, Then Lower Peritoneal, Then Subcutaneous Ultra-fast acting insulin will be injected into the upper peritoneum then lower peritoneum then subcutaneous space.	Lower Peritoneal, Then Upper Peritoneal, Then Subcutaneous Ultra-fast acting insulin will be injected into the lower peritoneum then upper peritoneum then subcutaneous space.
Week 1 (First Injection) STARTED	10	6
Week 1 (First Injection) Received Injection	10	6
Week 1 (First Injection) Received Disallowed Medication Prior to Injection	0	1
Week 1 (First Injection) Suspension of Basal Insulin > 2 Hours Prior to Injection	1	1
Week 1 (First Injection) Achieved Induced Hypoglycemia	4	4
Week 1 (First Injection) COMPLETED	10	5
Week 1 (First Injection) NOT COMPLETED	0	1
Week 2 (Second Injection) STARTED	10	5
Week 2 (Second Injection) Suspension of Basal Insulin > 2 Hours Prior to Injection	1	1
Week 2 (Second Injection) Achieved Induced Hypoglycemia	7	4
Week 2 (Second Injection) COMPLETED	10	5
Week 2 (Second Injection) NOT COMPLETED	0	0
Week 3 (Third Injection) STARTED	10	5
Week 3 (Third Injection) Suspension of Basal Insulin > 2 Hours Prior to Injection	1	1
Week 3 (Third Injection) Achieved Induced Hypoglycemia	9	4
Week 3 (Third Injection) COMPLETED	10	5
Week 3 (Third Injection) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Upper Peritoneal, Then Lower Peritoneal, Then Subcutaneous Ultra-fast acting insulin will be injected into the upper peritoneum then lower peritoneum then subcutaneous space.	Lower Peritoneal, Then Upper Peritoneal, Then Subcutaneous Ultra-fast acting insulin will be injected into the lower peritoneum then upper peritoneum then subcutaneous space.
Week 1 (First Injection) Physician Decision	0	1

Baseline Characteristics

Evaluating the Benefits of Physiologic Insulin Delivery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Upper Peritoneal, Then Lower Peritoneal, Then Subcutaneous n=10 Participants Ultra-fast acting insulin will be injected into the upper peritoneum then lower peritoneum then subcutaneous space.	Lower Peritoneal, Then Upper Peritoneal, Then Subcutaneous n=6 Participants Ultra-fast acting insulin will be injected into the lower peritoneum then upper peritoneum then subcutaneous space.	Total n=16 Participants Total of all reporting groups
Age, Continuous	39.0 years STANDARD_DEVIATION 7.1 • n=5 Participants	38.8 years STANDARD_DEVIATION 11.7 • n=7 Participants	38.9 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	4 Participants n=7 Participants	14 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	10 Participants n=5 Participants	5 Participants n=7 Participants	15 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max

Population: Participants with successfully induced hypoglycemia at the respective study visit

Outcome measures

Outcome measures
Measure	Upper Peritoneal Injection n=8 Injections Ultra-fast acting insulin injected into the upper peritoneum	Lower Peritoneal Injection n=11 Injections Ultra-fast acting insulin injected into the lower peritoneum	Injection- All Peritoneal n=19 Injections Ultra-fast acting insulin injected into the peritoneum	Subcutaneous Injection n=13 Injections Ultra-fast acting insulin injected subcutaneously
Glucagon Response to Induced Hypoglycemia	4.8 pg/mL Interval 2.7 to 8.2	8.8 pg/mL Interval 3.4 to 12.8	5.8 pg/mL Interval 3.0 to 9.1	4.2 pg/mL Interval 2.3 to 6.3

SECONDARY outcome

Timeframe: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max

Population: Participants were excluded if they took a disallowed medication, or if the suspension of basal insulin prior to injection exceeded 2 hours.

We will assess the maximum concentration of circulating insulin for each injection site after a median injection of 40% of each participant's total daily dose (approximately 0.25 units per kilogram of body weight). Analysis includes reporting groups for each type of injection, and upper and lower peritoneal injections combined (Injection- All Peritoneal).

Outcome measures

Outcome measures
Measure	Upper Peritoneal Injection n=13 Injections Ultra-fast acting insulin injected into the upper peritoneum	Lower Peritoneal Injection n=13 Injections Ultra-fast acting insulin injected into the lower peritoneum	Injection- All Peritoneal n=26 Injections Ultra-fast acting insulin injected into the peritoneum	Subcutaneous Injection n=13 Injections Ultra-fast acting insulin injected subcutaneously
Insulin Maximum Concentration in Plasma	56.81 mU/L Interval 46.4 to 63.49	63.26 mU/L Interval 37.6 to 78.84	56.95 mU/L Interval 44.01 to 77.57	57.47 mU/L Interval 46.84 to 69.53

SECONDARY outcome

Timeframe: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max

Population: Participants were excluded if they took a disallowed medication, or if the suspension of basal insulin prior to injection exceeded 2 hours.

We will compare the number of rescue treatments (2.5ml/kg 10% Dextrose) required to treat hypoglycemia \<50mg/dl for each injection location of approximately 0.25u/kg ultra-rapid insulin. Analysis includes reporting groups for each type of injection, and upper and lower peritoneal injections combined (Injection- All Peritoneal).

Outcome measures

Outcome measures
Measure	Upper Peritoneal Injection n=13 Injections Ultra-fast acting insulin injected into the upper peritoneum	Lower Peritoneal Injection n=13 Injections Ultra-fast acting insulin injected into the lower peritoneum	Injection- All Peritoneal n=26 Injections Ultra-fast acting insulin injected into the peritoneum	Subcutaneous Injection n=13 Injections Ultra-fast acting insulin injected subcutaneously
Hypoglycemic Treatments Required as a Measure of Glucose Values	1 Treatments Interval 0.0 to 2.0	1 Treatments Interval 1.0 to 1.0	1 Treatments Interval 0.0 to 1.0	3 Treatments Interval 3.0 to 4.0

SECONDARY outcome

Timeframe: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max

Population: Participants were excluded if they took a disallowed medication, or if the suspension of basal insulin prior to injection exceeded 2 hours.

We will assess time until the maximum concentration of circulating insulin for each injection site after a median injection of 40% of each participant's total daily dose (approximately 0.25 units per kilogram of body weight). Analysis includes reporting groups for each type of injection, and upper and lower peritoneal injections combined (Injection- All Peritoneal).

Outcome measures

Outcome measures
Measure	Upper Peritoneal Injection n=13 Injections Ultra-fast acting insulin injected into the upper peritoneum	Lower Peritoneal Injection n=13 Injections Ultra-fast acting insulin injected into the lower peritoneum	Injection- All Peritoneal n=26 Injections Ultra-fast acting insulin injected into the peritoneum	Subcutaneous Injection n=13 Injections Ultra-fast acting insulin injected subcutaneously
Time Until Maximum Insulin Concentration in Plasma	35 minutes Interval 25.0 to 40.0	25 minutes Interval 20.0 to 40.0	30 minutes Interval 20.0 to 40.0	60 minutes Interval 45.0 to 75.0

Adverse Events

Upper Peritoneal Injection

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Lower Peritoneal Injection

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Subcutaneous Injection

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Rayhan Lal

Stanford University

Phone: 650-725-2908

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place