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

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ClinicalTrials.gov Identifier: NCT03433677
Recruitment Status : Completed
First Posted : February 14, 2018
Results First Posted : October 8, 2019
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Type 1
Interventions Drug: LY900014
Drug: Insulin lispro
Enrollment 49
Recruitment Details  
Pre-assignment Details 2-period crossover with no washout between periods and a 4 week safety follow-up.
Arm/Group Title Sequence 1 (LY900014/Insulin Lispro) Sequence 2 (Insulin Lispro/LY900014)
Hide Arm/Group Description
  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
  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 Title: Period 1
Started 24 25
Received at Least 1 Dose of Study Drug 24 25
Completed 23 25
Not Completed 1 0
Reason Not Completed
Protocol Violation             1             0
Period Title: Period 2
Started 23 25
Received at Least 1 Dose of Study Drug 23 25
Completed 22 24
Not Completed 1 1
Reason Not Completed
Withdrawal by Subject             1             1
Arm/Group Title Sequence 1 (LY900014/Insulin Lispro) Sequence 2 (Insulin Lispro/LY900014) Total
Hide Arm/Group Description
  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
  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 of all reporting groups
Overall Number of Baseline Participants 24 25 49
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 25 participants 49 participants
42.50  (12.47) 36.72  (10.37) 39.55  (11.69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 25 participants 49 participants
Female 12 14 26
Male 12 11 23
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 25 participants 49 participants
Hispanic or Latino 1 0 1
Not Hispanic or Latino 23 25 48
Unknown or Not Reported 0 0 0
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 25 participants 49 participants
American Indian or Alaska Native 0 0 0
Asian 0 0 0
Native Hawaiian or Other Pacific Islander 0 0 0
Black or African American 1 0 1
White 23 25 48
More than one race 0 0 0
Unknown or Not Reported 0 0 0
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 24 participants 25 participants 49 participants
United States 10 11 21
Spain 14 14 28
1.Primary Outcome
Title Rate of Infusion Set Failures
Hide Description 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.
Time Frame 6 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Insulin Lispro (Humalog®) LY900014
Hide Arm/Group Description:
100 U/mL insulin lispro (Humalog®) administered by CSII
100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Overall Number of Participants Analyzed 48 49
Measure Type: Number
Unit of Measure: events per 30 participant days
0.05 0.03
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro (Humalog®), LY900014
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.375
Comments [Not Specified]
Method Wilcoxon signed-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
0.00 to 0.00
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With at Least 1 Event of Infusion Set Failure
Hide Description 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.
Time Frame 6 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Insulin Lispro (Humalog®) LY900014
Hide Arm/Group Description:
100 U/mL Insulin lispro (Humalog®) administered by CSII
100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Overall Number of Participants Analyzed 48 49
Measure Type: Number
Unit of Measure: percentage of participants
6.3 4.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro (Humalog®), LY900014
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.468
Comments [Not Specified]
Method Prescott's Exact test
Comments [Not Specified]
3.Secondary Outcome
Title Rate of Premature Infusion Set Changes
Hide Description Rate of premature infusion set changes.
Time Frame 6 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Insulin Lispro (Humalog®) LY900014
Hide Arm/Group Description:
100 U/mL insulin lispro (Humalog®) administered by CSII
100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Overall Number of Participants Analyzed 48 49
Measure Type: Number
Unit of Measure: events per 30 participant days
0.78 1.13
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro (Humalog®), LY900014
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.028
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Secondary Outcome
Title Time Interval Until Infusion Set Change
Hide Description 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).
Time Frame 6 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Lispro (Humalog®) LY900014
Hide Arm/Group Description:
100 U/mL insulin lispro (Humalog®) administered by CSII
100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Overall Number of Participants Analyzed 46 47
Least Squares Mean (Standard Error)
Unit of Measure: hours
76.1  (1.52) 74.3  (1.51)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro (Humalog®), LY900014
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.304
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean Difference
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-5.3 to 1.7
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Ratio of Bolus/Total Insulin Dose
Hide Description 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.
Time Frame 6 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Lispro (Humalog®) LY900014
Hide Arm/Group Description:
100 U/mL insulin lispro (Humalog®) administered by CSII
100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Overall Number of Participants Analyzed 47 46
Least Squares Mean (Standard Error)
Unit of Measure: percentage of total insulin dose
46.6  (1.17) 44.2  (1.17)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro (Humalog®), LY900014
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.057
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean Difference
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-4.8 to 0.1
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Interstitial Glucose Reduction Rate From Hyperglycemia Following a Non-Meal-Related Correction Bolus Delivered Via the Pump
Hide Description 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).
Time Frame 6 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Lispro (Humalog®) LY900014
Hide Arm/Group Description:
100 U/mL insulin lispro (Humalog®) administered by CSII
100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Overall Number of Participants Analyzed 37 37
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL/min
0.71  (0.062) 0.82  (0.063)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro (Humalog®), LY900014
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.177
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMeans
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
-0.05 to 0.27
Estimation Comments LSMean Difference
7.Secondary Outcome
Title Number of Participants With Severe Hypoglycemic Events
Hide Description 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]).
Time Frame 6 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Insulin Lispro (Humalog®) LY900014
Hide Arm/Group Description:
100 U/mL insulin lispro (Humalog®) administered by CSII
100 U/mL LY900014 administered by continuous subcutaneous insulin infusion (CSII)
Overall Number of Participants Analyzed 48 49
Measure Type: Number
Unit of Measure: participants
1 1
Time Frame up to 12 weeks
Adverse Event Reporting Description All randomized participants who received at least 1 dose of study drug.
 
Arm/Group Title LY900014 Insulin Lispro (Humalog®)
Hide Arm/Group Description LY900014 administered by continuous subcutaneous insulin infusion (CSII) Insulin lispro (Humalog®) administered by CSII
All-Cause Mortality
LY900014 Insulin Lispro (Humalog®)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/49 (0.00%)      0/48 (0.00%)    
Hide Serious Adverse Events
LY900014 Insulin Lispro (Humalog®)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/49 (2.04%)      1/48 (2.08%)    
Metabolism and nutrition disorders     
Hypoglycaemia † 1  1/49 (2.04%)  1 1/48 (2.08%)  1
1
Term from vocabulary, MedDRA 21.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
LY900014 Insulin Lispro (Humalog®)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/49 (36.73%)      6/48 (12.50%)    
General disorders     
Infusion site pain † 1  9/49 (18.37%)  11 2/48 (4.17%)  2
Infusion site reaction † 1  9/49 (18.37%)  36 4/48 (8.33%)  5
1
Term from vocabulary, MedDRA 21.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
EMail: Clinicaltrials.gov@lilly.com
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03433677    
Other Study ID Numbers: 16908
I8B-MC-ITSI ( Other Identifier: Eli Lilly and Company )
2017-002374-39 ( EudraCT Number )
First Submitted: February 9, 2018
First Posted: February 14, 2018
Results First Submitted: September 2, 2019
Results First Posted: October 8, 2019
Last Update Posted: October 8, 2019