Assessment of Mealtime Bolus Insulin Behavior

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03368807
• Collaborator: (none)
• Enrollment: 79
• Locations: 6
• Actual Duration (Months): 7.4
• Patients Per Site: 13.2
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The main purpose of this study is to estimate missed bolus insulin doses in diabetics. This is a 12-week, single-arm, outpatient, exploratory study with two study periods in Type 1 or Type 2 diabetics, with an investigational reusable injection pen, insulin, and a Continuous Glucose Monitoring (CGM) device.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2	Device: Continuous Glucose Monitoring; Drug: Insulin Lispro

Study Design

• Study Type: Observational
• Actual Enrollment: 79 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: An Objective Assessment of Mealtime Bolus Insulin Behavior and Associated Factors
• Actual Study Start Date: Dec 11, 2017
• Actual Primary Completion Date: Jun 12, 2018
• Actual Study Completion Date: Jul 23, 2018

Arms and Interventions

Arm	Intervention/Treatment
Blinded CGM (Continuous Glucose Monitoring) Participants received Insulin lispro 100 U/mL (units per millilitre) injected via the pen and they were blinded to CGM device recording as directed in study period 1.	Device: Continuous Glucose Monitoring; Commercially available; Drug: Insulin Lispro; As prescribed.
Unblinded CGM Participants received Insulin lispro 100 U/mL injected via the pen and they were unblinded to CGM device recording as directed in study period 2.	Device: Continuous Glucose Monitoring; Commercially available; Drug: Insulin Lispro; As prescribed.

Outcome Measures

Primary Outcome Measures

1. Average Number of Days Per Month With a Missed Bolus Insulin Dose With Blinded CGM [Week 1 up to 6 weeks]

   The average number of days per month with a missed bolus insulin dose was calculated in participants with Type 1 Diabetes or Type 2 Diabetes using blinded CGM measurements and the pen. The time of insulin dosing and glucose excursions were assessed using the display times recorded by the pen and CGM devices, respectively.

Secondary Outcome Measures

1. Average Number of Days Per Month With a Missed Bolus Insulin Dose With Unblinded CGM [Week 6 up to 12 weeks]

   The average number of days per month with a missed bolus insulin dose was calculated in participants with Type 1 Diabetes or Type 2 Diabetes using unblinded CGM measurements and the pen. The time of insulin dosing and glucose excursions were assessed using the display times recorded by the pen and CGM devices, respectively

2. Percentage of Time-in-Range (Glucose >70 and ≤180 Milligrams Per Deciliter) With Blinded CGM [Baseline up to 6 weeks]

   Percentage of time-in-range (glucose >70 and ≤180 milligrams per deciliter) was calculated in participants with Type 1 Diabetes or Type 2 Diabetes based on blinded CGM data collected in the study period. The time component of the time-in-range statistic was calculated using the display time recorded by the CGM device.

3. Percentage of Time-in-Range (Glucose >70 and ≤180 Milligrams Per Deciliter) With Unblinded CGM [Week 6 up to 12 weeks]

   Percentage of time-in-range (glucose >70 and ≤180 milligrams per deciliter) was calculated in participants with Type 1 Diabetes or Type 2 Diabetes based on unblinded CGM data collected in the study period. The time component of the time-in-range statistic was calculated using the display time recorded by the CGM device.

4. Percentage of Missed Bolus Doses Per Month With Blinded CGM [Baseline up to 6 weeks]

   Percentage of missed bolus doses per month was estimated in participants with Type 1 diabetes or Type 2 diabetes using blinded CGM measurements and the pen.

5. Percentage of Missed Bolus Doses Per Month With Unblinded CGM [Week 6 up to 12 weeks]

   Percentage of missed bolus doses per month was estimated in participants with Type 1 diabetes or Type 2 diabetes using unblinded CGM measurements and the pen.

6. Average Number of Missed Bolus Insulin Doses Per Day With Blinded CGM [Baseline up to 6 weeks]

   The average number of missed bolus doses per day was estimated in participants with Type 1 diabetes or Type 2 diabetes using blinded CGM measurements and the pen.

7. Average Number of Missed Bolus Insulin Doses Per Day With Unblinded CGM [Week 6 up to 12 weeks]

   The average number of missed bolus doses per day was estimated in participants with Type 1 diabetes or Type 2 diabetes using unblinded CGM data.

8. Average Number of Missed and Suboptimal Bolus Dose (MSBD) Events Per Month With Blinded CGM [Baseline up to 6 weeks]

   The number of Missed and Suboptimal Doses (MSBDs) per month was calculated in participants with Type 1 Diabetes or Type 2 Diabetes as the sum of the identified missed bolus doses and suboptimal bolus doses for each participant for each period.

9. Average Number of Missed and Suboptimal Bolus Dose (MSBD) Events Per Month With Unblinded CGM [Week 6 up to 12 weeks]

   The number of Missed and Suboptimal Doses (MSBDs) per month was calculated in participants with Type 1 Diabetes or Type 2 Diabetes as the sum of the identified missed bolus doses and suboptimal bolus doses for each participant for each period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have a Type 1 Diabetes Mellitus (T1D) or a Type 2 Diabetes Mellitus (T2D) diagnosis

• Must be taking a mealtime bolus dose insulin, greater than or equal to (≥) 3 doses

• Each individual bolus insulin dose must be less than (<) 40 units

• Must be taking a stable insulin dose regimen for the last 3 months

• Must be taking a bolus insulin analog (for example insulin lispro [U-100]/[U-200], insulin aspart, or insulin glulisine). In addition, must be able to switch to insulin lispro U-100 for the duration of the trial

• Must have a hemoglobin A1c (HbA1c) ≥8.0% in the last 6 months

• Participants with T1D must be ≥21 to less than or equal to (≤) 65 years of age. Participants with T2D must be ≥35 to ≤65 years of age

• Women of childbearing potential must meet the following: (Note: females of childbearing potential are defined as those who have experienced menarche and who are NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause)

• Must agree to use 1 highly effective method of contraception, or a combination of 2 effective methods of contraception for the entirety of the study

• Must test negative for pregnancy as indicated by a negative serum or urine pregnancy test

• Participants with prior CGM/flash glucose monitoring experience must have stopped CGM/flash glucose monitoring ≥3 months prior to enrollment

Exclusion Criteria:

• Have known tape/adhesive allergies with CGM sensors

• Medical conditions, visual, physical, psychiatric, or cognitive impairment(s) that may preclude the ability to participate in the trial

• Have history of liver disease, acute or chronic hepatitis, or alanine aminotransferase or aspartate aminotransferase levels ≥3 times the upper limit of the reference range within the last 6 months

• Have history of chronic kidney disease stage 4 and higher within the last 6 months, or history of renal transplantation

• Have active malignancy

• Are pregnant or planning to become pregnant

• Are on or are intending to begin a weight loss program

• Participants with T1D who have taken off-label antihyperglycemic agents within last 3 months

• Have received insulin by continuous subcutaneous insulin infusion in the last 3 months

• Participants taking opioid medications for medically invalid reasons or at doses considered excessive

• Participants on routine use of acetaminophen

• Currently undergoing systemic treatment with:

• Immunosuppressive medication

• Chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within the prior 2 weeks

• Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study

• Have participated, within the last 30 days, in a clinical study involving an investigational product

• Are unwilling or unable to comply with the use of a data collection device to directly record data

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AMCR Institute, Inc.	Escondido	California	United States	92025
2	Science 37 Inc	Los Angeles	California	United States	90045
3	Coastal Metabolic Research Ctr	Ventura	California	United States	93003
4	Rocky Mountain Diabetes and Osteoporosis Center	Idaho Falls	Idaho	United States	83404
5	Iowa Diabetes & Endocrinology Research Center	West Des Moines	Iowa	United States	50265
6	Advanced Research Institute	Ogden	Utah	United States	84405

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Nov 20, 2017
• Statistical Analysis Plan - Aug 1, 2018

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03368807
• Other Study ID Numbers: 16866; F3Z-MC-IOQV
• First Posted: Dec 11, 2017
• Last Update Posted: Aug 2, 2019
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Insulin Lispro

Study Results

Participant Flow

Arm/Group Title	Study Period 1/Study Period 2
Arm/Group Description	Participants with type 1 diabetes or type 2 diabetes received prescribed insulin regimen suitable for their disease state using insulin lispro 100 units per millilitre (U/mL) injected via the pen. During the study, participants had their glucose monitored via the continuous glucose monitoring (CGM) device, which was blinded during Study Period 1 and unblinded during Study Period 2.
Period Title: Period 1 (Blinded CGM)
STARTED	79
Received at Least 1 Dose of Study Drug	78
COMPLETED	73
NOT COMPLETED	6
Period Title: Period 1 (Blinded CGM)
STARTED	73
COMPLETED	73
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	Participants received prescribed insulin regimen suitable for their disease state using insulin lispro 100 U/mL injected via the pen. During the study, participants had their glucose monitored via the CGM device, which was blinded during Study Period 1 and unblinded during Study Period 2.
Overall Participants	79
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	48.01 (11.71)
Sex: Female, Male (Count of Participants)
Female	36 45.6%
Male	43 54.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 16.5%
Not Hispanic or Latino	66 83.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.3%
Asian	1 1.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 3.8%
White	73 92.4%
More than one race	1 1.3%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	79 100%
Body Mass Index (BMI) (kg/m²) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m²]	30.9 (6.1)

Outcome Measures

1. Primary Outcome

Title	Average Number of Days Per Month With a Missed Bolus Insulin Dose With Blinded CGM
Description	The average number of days per month with a missed bolus insulin dose was calculated in participants with Type 1 Diabetes or Type 2 Diabetes using blinded CGM measurements and the pen. The time of insulin dosing and glucose excursions were assessed using the display times recorded by the pen and CGM devices, respectively.
Time Frame	Week 1 up to 6 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and have missed bolus insulin dose data.

Arm/Group Title	Blinded CGM
Arm/Group Description	Participants received Insulin lispro 100 U/mL injected via the pen and they were blinded to CGM device recording as directed.
Measure Participants	68
Mean (Standard Deviation) [Days per month]	19.3 (6.2)

2. Secondary Outcome

Title	Average Number of Days Per Month With a Missed Bolus Insulin Dose With Unblinded CGM
Description	The average number of days per month with a missed bolus insulin dose was calculated in participants with Type 1 Diabetes or Type 2 Diabetes using unblinded CGM measurements and the pen. The time of insulin dosing and glucose excursions were assessed using the display times recorded by the pen and CGM devices, respectively
Time Frame	Week 6 up to 12 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and have missed bolus insulin dose data.

Arm/Group Title	Unblinded CGM
Arm/Group Description	Participants received Insulin lispro 100 U/mL injected via the pen and they were unblinded to CGM device recording as directed.
Measure Participants	65
Mean (Standard Deviation) [Days per month]	17.9 (5.7)

3. Secondary Outcome

Title	Percentage of Time-in-Range (Glucose >70 and ≤180 Milligrams Per Deciliter) With Blinded CGM
Description	Percentage of time-in-range (glucose >70 and ≤180 milligrams per deciliter) was calculated in participants with Type 1 Diabetes or Type 2 Diabetes based on blinded CGM data collected in the study period. The time component of the time-in-range statistic was calculated using the display time recorded by the CGM device.
Time Frame	Baseline up to 6 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and have data for Percentage of Time-in-Range.

Arm/Group Title	Blinded CGM
Arm/Group Description	Participants received Insulin lispro 100 U/mL injected via the pen and they were blinded to CGM device recording as directed.
Measure Participants	68
Mean (Standard Deviation) [Percentage of time]	42.7 (18.8)

4. Secondary Outcome

Title	Percentage of Time-in-Range (Glucose >70 and ≤180 Milligrams Per Deciliter) With Unblinded CGM
Description	Percentage of time-in-range (glucose >70 and ≤180 milligrams per deciliter) was calculated in participants with Type 1 Diabetes or Type 2 Diabetes based on unblinded CGM data collected in the study period. The time component of the time-in-range statistic was calculated using the display time recorded by the CGM device.
Time Frame	Week 6 up to 12 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and have data for Percentage of Time-in-Range.

Arm/Group Title	Unblinded CGM
Arm/Group Description	Participants received Insulin lispro 100 U/mL injected via the pen and they were unblinded to CGM device recording as directed.
Measure Participants	65
Mean (Standard Deviation) [Percentage of time]	49.6 (20.0)

5. Secondary Outcome

Title	Percentage of Missed Bolus Doses Per Month With Blinded CGM
Description	Percentage of missed bolus doses per month was estimated in participants with Type 1 diabetes or Type 2 diabetes using blinded CGM measurements and the pen.
Time Frame	Baseline up to 6 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and have data for missed bolus doses.

Arm/Group Title	Blinded CGM
Arm/Group Description	Participants received Insulin lispro 100 U/mL injected via the pen and they were blinded to CGM device recording as directed.
Measure Participants	68
Mean (Standard Deviation) [Percentage of missed bolus dose]	25.3 (12.3)

6. Secondary Outcome

Title	Percentage of Missed Bolus Doses Per Month With Unblinded CGM
Description	Percentage of missed bolus doses per month was estimated in participants with Type 1 diabetes or Type 2 diabetes using unblinded CGM measurements and the pen.
Time Frame	Week 6 up to 12 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and have data for missed bolus doses.

Arm/Group Title	Unblinded CGM
Arm/Group Description	Participants received Insulin lispro 100 U/mL injected via the pen and they were unblinded to CGM device recording as directed.
Measure Participants	65
Mean (Standard Deviation) [Percentage of missed bolus dose]	23.3 (10.2)

7. Secondary Outcome

Title	Average Number of Missed Bolus Insulin Doses Per Day With Blinded CGM
Description	The average number of missed bolus doses per day was estimated in participants with Type 1 diabetes or Type 2 diabetes using blinded CGM measurements and the pen.
Time Frame	Baseline up to 6 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and have data for missed bolus doses.

Arm/Group Title	Blinded CGM
Arm/Group Description	Participants received Insulin lispro 100 U/mL injected via the pen and they were blinded to CGM device recording as directed.
Measure Participants	68
Mean (Standard Deviation) [Dose per day]	0.9 (0.4)

8. Secondary Outcome

Title	Average Number of Missed Bolus Insulin Doses Per Day With Unblinded CGM
Description	The average number of missed bolus doses per day was estimated in participants with Type 1 diabetes or Type 2 diabetes using unblinded CGM data.
Time Frame	Week 6 up to 12 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and have data for missed bolus doses.

Arm/Group Title	Unblinded CGM
Arm/Group Description	Participants received Insulin lispro 100 U/mL injected via the pen and they were unblinded to CGM device recording as directed.
Measure Participants	65
Mean (Standard Deviation) [Dose per day]	0.9 (0.4)

9. Secondary Outcome

Title	Average Number of Missed and Suboptimal Bolus Dose (MSBD) Events Per Month With Blinded CGM
Description	The number of Missed and Suboptimal Doses (MSBDs) per month was calculated in participants with Type 1 Diabetes or Type 2 Diabetes as the sum of the identified missed bolus doses and suboptimal bolus doses for each participant for each period.
Time Frame	Baseline up to 6 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and have data for missed bolus doses.

Arm/Group Title	Blinded CGM
Arm/Group Description	Participants received Insulin lispro 100 U/mL injected via the pen and they were blinded to CGM device recording as directed.
Measure Participants	68
Mean (Standard Deviation) [Dose per month]	68.3 (24.1)

10. Secondary Outcome

Title	Average Number of Missed and Suboptimal Bolus Dose (MSBD) Events Per Month With Unblinded CGM
Description	The number of Missed and Suboptimal Doses (MSBDs) per month was calculated in participants with Type 1 Diabetes or Type 2 Diabetes as the sum of the identified missed bolus doses and suboptimal bolus doses for each participant for each period.
Time Frame	Week 6 up to 12 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and have data for missed bolus doses.

Arm/Group Title	Unblinded CGM
Arm/Group Description	Participants received Insulin lispro 100 U/mL injected via the pen and they were unblinded to CGM device recording as directed.
Measure Participants	65
Mean (Standard Deviation) [Dose per month]	61.9 (22.2)

Adverse Events

Time Frame	Up To 12 Weeks
Adverse Event Reporting Description	All enrolled participants who received at least one dose of study drug.
Arm/Group Title	Blinded CGM		Unblinded CGM
Arm/Group Description	Participants received Insulin lispro 100 U/mL injected via the pen and they were blinded to CGM device recording as directed.		Participants received Insulin lispro 100 U/mL injected via the pen and they were unblinded to CGM device recording as directed.
All Cause Mortality
	Blinded CGM		Unblinded CGM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/78 (0%)		0/73 (0%)
Serious Adverse Events
	Blinded CGM		Unblinded CGM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/78 (3.8%)		2/73 (2.7%)
General disorders
Chest pain	1/78 (1.3%)	1	0/73 (0%)	0
Infections and infestations
Localised infection	0/78 (0%)	0	2/73 (2.7%)	2
Metabolism and nutrition disorders
Hypoglycaemia	1/78 (1.3%)	1	0/73 (0%)	0
Surgical and medical procedures
Medical device removal	1/78 (1.3%)	1	0/73 (0%)	0
Other (Not Including Serious) Adverse Events
	Blinded CGM		Unblinded CGM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/78 (28.2%)		9/73 (12.3%)
Cardiac disorders
Bradycardia	0/78 (0%)	0	1/73 (1.4%)	1
Ear and labyrinth disorders
Vertigo	1/78 (1.3%)	1	0/73 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/78 (1.3%)	1	0/73 (0%)	0
Impaired gastric emptying	1/78 (1.3%)	1	0/73 (0%)	0
General disorders
Application site bruise	1/78 (1.3%)	1	0/73 (0%)	0
Application site pain	1/78 (1.3%)	1	0/73 (0%)	0
Chest pain	0/78 (0%)	0	1/73 (1.4%)	1
Vessel puncture site bruise	1/78 (1.3%)	1	0/73 (0%)	0
Infections and infestations
Bronchitis	1/78 (1.3%)	1	0/73 (0%)	0
Gastroenteritis viral	1/78 (1.3%)	1	0/73 (0%)	0
Influenza	3/78 (3.8%)	3	1/73 (1.4%)	1
Nasopharyngitis	1/78 (1.3%)	1	1/73 (1.4%)	1
Onychomycosis	0/78 (0%)	0	1/73 (1.4%)	1
Respiratory tract infection	1/78 (1.3%)	1	0/73 (0%)	0
Upper respiratory tract infection	3/78 (3.8%)	3	0/73 (0%)	0
Viral infection	1/78 (1.3%)	1	0/73 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	1/78 (1.3%)	1	0/73 (0%)	0
Foot fracture	1/78 (1.3%)	1	0/73 (0%)	0
Humerus fracture	0/78 (0%)	0	1/73 (1.4%)	1
Joint injury	1/78 (1.3%)	1	0/73 (0%)	0
Limb injury	1/78 (1.3%)	1	0/73 (0%)	0
Investigations
Blood cholesterol increased	1/78 (1.3%)	1	0/73 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	0/78 (0%)	0	1/73 (1.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/78 (1.3%)	1	0/73 (0%)	0
Musculoskeletal pain	1/78 (1.3%)	1	0/73 (0%)	0
Nervous system disorders
Nerve compression	1/78 (1.3%)	1	0/73 (0%)	0
Product Issues
Device damage	0/78 (0%)	0	1/73 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/78 (0%)	0	1/73 (1.4%)	1
Dyspnoea	1/78 (1.3%)	1	0/73 (0%)	0
Oropharyngeal pain	0/78 (0%)	0	1/73 (1.4%)	1
Respiratory tract congestion	1/78 (1.3%)	1	0/73 (0%)	0
Vascular disorders
Diabetic microangiopathy	1/78 (1.3%)	1	0/73 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Some investigators wait until a multi-site publication is published (or 2 years if not published sooner) plus a 90 day review period.