Trial Outcomes & Findings for A Study of LY900014 and Insulin Lispro With an External Continuous Subcutaneous Insulin Infusion System in Adult Participants With Type 1 Diabetes (NCT NCT03433677)

Last Updated: 2019-10-08

Results Overview

Infusion set failure events are defined as premature infusion set changes, due to a pump occlusion alarm OR due to unexplained hyperglycemia with blood glucose (SMBG) \>250 milligrams per deciliter (mg/dL) (13.9 millimoles per liter \[mmol/L\]) that does not decrease within 1 hour following a correction bolus delivered via the pump during the 6 week treatment period. Aggregate rate was calculated for each participant as the total number of events while the participant is on study treatment divided by the days of exposure \[last dose date and time -first dose date and time -duration of pump or treatment interruption\] times 30.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

49 participants

Primary outcome timeframe

6 Weeks

Results posted on

2019-10-08

Participant Flow

2-period crossover with no washout between periods and a 4 week safety follow-up.

Participant milestones

Participant milestones
Measure	Sequence 1 (LY900014/Insulin Lispro) 1. 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII) for six weeks 2. 100 U/mL insulin lispro (Humalog®) administered by CSII for six weeks with no washout between periods	Sequence 2 (Insulin Lispro/LY900014) 1. 100 U/mL insulin lispro (Humalog®) administered by CSII for 6 weeks 2. 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII) for six weeks with no washout between periods
Period 1 STARTED	24	25
Period 1 Received at Least 1 Dose of Study Drug	24	25
Period 1 COMPLETED	23	25
Period 1 NOT COMPLETED	1	0
Period 2 STARTED	23	25
Period 2 Received at Least 1 Dose of Study Drug	23	25
Period 2 COMPLETED	22	24
Period 2 NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 1 (LY900014/Insulin Lispro) 1. 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII) for six weeks 2. 100 U/mL insulin lispro (Humalog®) administered by CSII for six weeks with no washout between periods	Sequence 2 (Insulin Lispro/LY900014) 1. 100 U/mL insulin lispro (Humalog®) administered by CSII for 6 weeks 2. 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII) for six weeks with no washout between periods
Period 1 Protocol Violation	1	0
Period 2 Withdrawal by Subject	1	1

Baseline Characteristics

A Study of LY900014 and Insulin Lispro With an External Continuous Subcutaneous Insulin Infusion System in Adult Participants With Type 1 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence 1 (LY900014/Insulin Lispro) n=24 Participants 1. 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII) for six weeks 2. 100 U/mL insulin lispro (Humalog®) administered by CSII for six weeks with no washout between periods	Sequence 2 (Insulin Lispro/LY900014) n=25 Participants 1. 100 U/mL insulin lispro (Humalog®) administered by CSII for 6 weeks 2. 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII) for six weeks with no washout between periods	Total n=49 Participants Total of all reporting groups
Age, Continuous	42.50 years STANDARD_DEVIATION 12.47 • n=5 Participants	36.72 years STANDARD_DEVIATION 10.37 • n=7 Participants	39.55 years STANDARD_DEVIATION 11.69 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	25 Participants n=7 Participants	48 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	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	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	25 Participants n=7 Participants	48 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	11 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment Spain	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 Weeks

Population: All randomized participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog®) n=48 Participants 100 U/mL insulin lispro (Humalog®) administered by CSII	LY900014 n=49 Participants 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Rate of Infusion Set Failures	0.05 events per 30 participant days	0.03 events per 30 participant days

SECONDARY outcome

Timeframe: 6 Weeks

Population: All randomized participants who received at least 1 dose of study drug.

Infusion set failures are defined as premature infusion set changes, due to a pump occlusion alarm OR due to unexplained hyperglycemia with blood glucose (SMBG) \>250mg/dL (13.9 mmol/L) that does not decrease within 1 hour following a correction bolus delivered via the pump.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog®) n=48 Participants 100 U/mL insulin lispro (Humalog®) administered by CSII	LY900014 n=49 Participants 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Percentage of Participants With at Least 1 Event of Infusion Set Failure	6.3 percentage of participants	4.1 percentage of participants

SECONDARY outcome

Timeframe: 6 Weeks

Population: All randomized participants who received at least 1 dose of study drug.

Rate of premature infusion set changes.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog®) n=48 Participants 100 U/mL insulin lispro (Humalog®) administered by CSII	LY900014 n=49 Participants 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Rate of Premature Infusion Set Changes	0.78 events per 30 participant days	1.13 events per 30 participant days

SECONDARY outcome

Timeframe: 6 Weeks

Population: All randomized participants who received at least 1 dose of study drug and non-missing baseline value and at least one non-missing post-baseline value.

Time interval until infusion set change reflects the time interval in hours until infusion set change from first to last dose. MMRM model for post-baseline measures: Variable = Baseline + Period + Sequence + Strata(Region + Historical Use of SmartGuard/Threshold Suspend + HbA1c(\<=7.3%, \>7.3%)) + Treatment (Type III sum of squares).

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog®) n=46 Participants 100 U/mL insulin lispro (Humalog®) administered by CSII	LY900014 n=47 Participants 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Time Interval Until Infusion Set Change	76.1 hours Standard Error 1.52	74.3 hours Standard Error 1.51

SECONDARY outcome

Timeframe: 6 Weeks

Population: All randomized participants who received at least 1 dose of study drug and non-missing baseline value and at least one non-missing post-baseline value.

The bolus and total insulin doses for each visit was calculated as the mean of the doses for the last 3 days prior to the visit date that are entered in the eCRF. The bolus/total ratio was derived as the bolus dose divided by the total insulin dose at each visit.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog®) n=47 Participants 100 U/mL insulin lispro (Humalog®) administered by CSII	LY900014 n=46 Participants 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Ratio of Bolus/Total Insulin Dose	46.6 percentage of total insulin dose Standard Error 1.17	44.2 percentage of total insulin dose Standard Error 1.17

SECONDARY outcome

Timeframe: 6 Weeks

Population: All randomized participants who received at least 1 dose of study drug and non-missing baseline value and at least one non-missing post-baseline value of the response.

Interstitial glucose reduction rate (glucose reduction \[mg/dL\] per minute) within 4 hours following a non-meal-related correction bolus via the pump, from hyperglycemia (interstitial glucose \>180 mg/dL \[10 mmol/L\]) to recovery (interstitial glucose ≤180 mg/dL).

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog®) n=37 Participants 100 U/mL insulin lispro (Humalog®) administered by CSII	LY900014 n=37 Participants 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Interstitial Glucose Reduction Rate From Hyperglycemia Following a Non-Meal-Related Correction Bolus Delivered Via the Pump	0.71 mg/dL/min Standard Error 0.062	0.82 mg/dL/min Standard Error 0.063

SECONDARY outcome

Timeframe: 6 Weeks

Population: All randomized participants who received at least 1 dose of study drug.

Number of participants with severe hypoglycemic events. Severe hypoglycemia was defined as participants with an altered mental status and could not assist in their own care, may have been semiconscious or unconscious, or experienced coma with or without seizures, and the event required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Blood glucose measurements may not have been available during such an event, but neurological recovery attributable to the restoration of BG concentration to normal was considered sufficient evidence that the event was induced by a low BG concentration (BG ≤70 mg/dL \[3.9 mmol/L\]).

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog®) n=48 Participants 100 U/mL insulin lispro (Humalog®) administered by CSII	LY900014 n=49 Participants 100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Number of Participants With Severe Hypoglycemic Events	1 participants	1 participants

Adverse Events

LY900014

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Insulin Lispro (Humalog®)

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LY900014 n=49 participants at risk LY900014 administered by continuous subcutaneous insulin infusion (CSII)	Insulin Lispro (Humalog®) n=48 participants at risk Insulin lispro (Humalog®) administered by CSII
Metabolism and nutrition disorders Hypoglycaemia	2.0% 1/49 • Number of events 1 • up to 12 weeks All randomized participants who received at least 1 dose of study drug.	2.1% 1/48 • Number of events 1 • up to 12 weeks All randomized participants who received at least 1 dose of study drug.

Other adverse events

Other adverse events
Measure	LY900014 n=49 participants at risk LY900014 administered by continuous subcutaneous insulin infusion (CSII)	Insulin Lispro (Humalog®) n=48 participants at risk Insulin lispro (Humalog®) administered by CSII
General disorders Infusion site pain	18.4% 9/49 • Number of events 11 • up to 12 weeks All randomized participants who received at least 1 dose of study drug.	4.2% 2/48 • Number of events 2 • up to 12 weeks All randomized participants who received at least 1 dose of study drug.
General disorders Infusion site reaction	18.4% 9/49 • Number of events 36 • up to 12 weeks All randomized participants who received at least 1 dose of study drug.	8.3% 4/48 • Number of events 5 • up to 12 weeks All randomized participants who received at least 1 dose of study drug.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60