Safety Evaluation of an Advanced Hybrid Closed Loop System Using Lyumjev With the Tandem t:Slim X2 Insulin Pump With Control-IQ Technology in Adults, Adolescents and Children With Type 1 Diabetes

Prospective, multi-center, single-arm study in adults and children ages 6 to 80 with type 1 diabetes to evaluate the safety of Lyumjev with Control-IQ technology to achieve labeling updates for Lyumjev and the t:slim X2 insulin pump.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: t:slim X2 insulin pump with Control-IQ technology 1.5

Detailed Description

This is a prospective, multi-center, single-arm study in adults and children (ages 6 to 80 years) with type 1 diabetes who are current users of the t:slim X2 insulin pump with Control-IQ technology to achieve labeling updates for Lyumjev and the t:slim X2 insulin pump. After a run-in period, participants will use the study pump with Control-IQ technology 1.5 and Lyumjev insulin for a 3-month outpatient treatment period. Up to 200 participants will be enrolled so at least 160 complete the study.

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Children's Hospital Orange County
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida Diabetes Center
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University / Riley Hospital for Children
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Iowa Diabetes and Endocrinology Research Center (IDERC)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mt. Sinai
  • Texas
    • San Antonio, Texas, United States, 78229
      • Diabetes & Glandular Disease (DGD)
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 6 to <81 years
2. Diagnosis of type 1 diabetes for at least 1 year
3. Currently using Control-IQ technology for at least 3 months, with CGM data recorded indicative of system use (active closed loop) for at least 85% of the possible time in 14 days prior to enrollment
4. Total daily insulin dose (TDD) at least 2 U/day
5. HbA1c < 10.5%
6. Residing full-time in the United States, with no anticipated travel outside the United States during the period of study participation.
7. For participants <18 years old, living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia and able to contact the participant in case of an emergency, and willing to use the Dexcom Follow app (with push notifications turned on) for the duration of the study.
8. If >18 years old, participant has someone who lives within 30 minutes of them who is willing to be contacted if the study team can't reach the participant in case of a suspected medical emergency.

9. Participant has agreed to participate in the study; and has read, understood and signed the informed consent form (ICF) and assent, if applicable; and has agreed to follow all study procedures, including:

   1. suspending use of any personal CGM for the duration of the clinical trial once the study CGM is in use
   2. switching to or continuing to use Humalog during the lead-in period
   3. switching to Lyumjev for the main study period.
   4. willing and able to perform the study exercise and meal challenges.
10. Investigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocol, including ability to respond to alerts and alarms, and to provide basic diabetes self-management.
11. Participant and/or parent/legal guardian have the ability to read and understand English

Exclusion Criteria:

1. More than 1 episode of diabetic ketoacidosis (DKA) in the past 6 months
2. More than 1 episode of severe hypoglycemia (needing assistance) in the past 6 months
3. Inpatient psychiatric treatment in the past 6 months
4. History of drug abuse (defined as any illicit drug use) or history of alcohol abuse prior to screening or unwillingness to agree to abstain from illicit drugs throughout the study.

5. For Female: Currently pregnant or planning to become pregnant during the time period of study participation

   1. A negative pregnancy test will be required for all females of child-bearing potential (menarchal)
   2. Counseling on appropriate birth control options will be provided to females with child-bearing potential in the event the participant does not have an acceptable plan.
6. Adults lacking the capacity to provide consent and/or follow study procedures in the opinion of the investigator
7. Concurrent use of any non-insulin glucose-lowering agent, other than metformin (for example, GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas).
8. Hemophilia or any other bleeding disorder
9. Hemoglobinopathy
10. History of heart, liver, lung or kidney disease determined by investigator to interfere with the study
11. History of allergic reaction to Humalog or Lyumjev
12. Use of glucocorticoids, beta blockers or other medications determined by investigator to interfere with study
13. Abnormal screening electrocardiogram consistent with increased risk during exercise, such as arrhythmia, ischemia, or prolonged QTc interval (>450 ms) (Screening ECG only required for participants age > 50 years, duration of diabetes > 20 years, or history of coronary artery disease)
14. Significant chronic kidney disease (which could impact CGM accuracy in investigator's judgment) or hemodialysis
15. History of adrenal insufficiency
16. History of abnormal TSH consistent with hypothyroidism or hyperthyroidism that is not appropriately treated
17. History of gastroparesis
18. A condition, which in the opinion of the investigator or designee, would put the participant or study at risk
19. Participation in another pharmaceutical or device trial at the time of enrollment or anticipated for during the time period of study participation
20. Employed by, or having immediate family members employed by Tandem Diabetes Care, Inc., Eli Lilly and Co., or TypeZero Technologies, LLC, or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: t:slim X2 insulin pump with Control-IQ technology utilizing insulin Lyumjev®; Current Control-IQ technology users with type 1 diabetes, age 6-80, will use the t:slim X2 insulin pump with Control-IQ technology 1.5 and Lyumjev insulin for 3-months of outpatient use.	Device: t:slim X2 insulin pump with Control-IQ technology 1.5; t:slim X2 insulin pump with Control-IQ technology 1.5, and wearing the Dexcom G6 sensor, used with Lyumjev® insulin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe Hypoglycemia	Number of severe hypoglycemia events (with cognitive impairment such that assistance of another individual is needed for treatment) during study	15 weeks
Diabetic Ketoacidosis	Number of diabetic ketoacidosis events requiring an overnight hospitalization and diagnosis by a doctor.	15 weeks
Unanticipated Adverse Device Effects	Number of unanticipated adverse device effects (UADE) events	15 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Percent Time Less Than 54 mg/dL	CGM overall percent time less than 54 mg/dL	15 Weeks
Postprandial Percent Time Less Than 54 mg/dL, Through 4 Hours After Each Meal	CGM postprandial percent time less than 54 mg/dL, through 4 hours after each meal. Calculated as mean (SD) over all 4 hour postprandial periods throughout the study.	during 4 hour postprandial period after each meal, up to 15 weeks
Overall Percent Time Less Than 70 mg/dL	CGM overall percent time less than 70 mg/dL	15 weeks
Postprandial Percent Time Less Than 70 mg/dL, Through 4 Hours After Each Meal	CGM postprandial percent time less than 70 mg/dL, through 4 hours after each meal. Calculated as mean (SD) over all 4 hour postprandial periods throughout the study.	during 4 hour postprandial period after each meal, up to 15 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Percent Time in Range Between 70-180 mg/dL	Overall CGM percent time in range between 70-180 mg/dL	15 weeks
Percent Time in Range Between 70-180 mg/dL, Daytime Only (6:00 AM - 11:59 PM)	CGM percent time in range between 70-180 mg/dL, daytime only (6:00 AM - 11:59 PM)	15 weeks
Percent Time in Range Between 70-180 mg/dL, Nighttime Only (12:00 AM - 5:59 AM)	CGM percent time in range between 70-180 mg/dL, nighttime only (12:00 AM - 5:59 AM)	15 weeks
Overall Percent Time in Range Between 70-140 mg/dL	Overall CGM percent time in range between 70-140 mg/dL	15 weeks
Percent Time in Range Between 70-140 mg/dL, Daytime Only (6:00 AM - 11:59 PM)	CGM percent time in range between 70-140 mg/dL, daytime only (6:00 AM - 11:59 PM)	15 weeks
Percent Time in Range Between 70-140 mg/dL, Nighttime Only (12:00 AM - 5:59 AM)	CGM percent time in range between 70-140 mg/dL, nighttime only (12:00 AM - 5:59 AM)	15 weeks
Overall Percent Time in Range Greater Than 180 mg/dL	Overall CGM percent time in range greater than 180 mg/dL	15 weeks
Percent Time in Range Greater Than 180 mg/dL, Daytime Only (6:00 AM - 11:59 PM)	CGM percent time in range greater than 180 mg/dL, daytime only (6:00 AM - 11:59 PM)	15 weeks
Percent Time in Range Greater Than 180 mg/dL, Nighttime Only (12:00 AM - 5:59 AM)	CGM percent time in range greater than 180 mg/dL, nighttime only (12:00 AM - 5:59 AM)	15 weeks
Overall Percent Time in Range Greater Than 250 mg/dL	Overall CGM percent time in range greater than 250 mg/dL	15 weeks
Percent Time in Range Greater Than 250 mg/dL, Daytime Only (6:00 AM - 11:59 PM)	CGM percent time in range greater than 250 mg/dL, daytime only (6:00 AM - 11:59 PM)	15 weeks
Percent Time in Range Greater Than 250 mg/dL, Nighttime Only (12:00 AM - 5:59 AM)	CGM percent time in range greater than 250 mg/dL, nighttime only (12:00 AM - 5:59 AM)	15 weeks
Overall CGM Hyperglycemic Events Per Week	Overall CGM hyperglycemic events per week, defined as 90 or more minutes greater than 300 mg/dL within a 120 minute window	15 weeks
CGM Hyperglycemic Events Per Week, Daytime Only (6:00 AM - 11:59 PM)	CGM hyperglycemic events per week, defined as 90 or more minutes greater than 300 mg/dL within 120 minute window, daytime only (6:00 AM - 11:59 PM)	15 weeks
CGM Hyperglycemic Events Per Week, Nighttime Only (12:00 AM - 5:59 AM)	CGM hyperglycemic events per week, defined as 90 or more minutes greater than 300 mg/dL within 120 minute window, nighttime only (12:00 AM - 5:59 AM)	15 weeks
Overall CGM Hypoglycemia Events Per Week	Overall CGM hypoglycemia events per week defined as 15 or more consecutive minutes less than 54 mg/dL	15 weeks
CGM Hypoglycemia Events Per Week, Daytime Only (6:00 AM - 11:59 PM)	CGM hypoglycemia events per week defined as 15 or more consecutive minutes less than 54 mg/dL, daytime only (6:00 AM - 11:59 PM)	15 weeks
CGM Hypoglycemia Events Per Week, Nighttime Only (12:00 AM - 5:59 AM)	CGM hypoglycemia events per week defined as 15 or more consecutive minutes less than 54 mg/dL, nighttime only (12:00 AM - 5:59 AM)	15 weeks
Overall Mean Glucose	Overall CGM mean glucose mg/dL	15 weeks
Mean Glucose, Daytime Only (6:00 AM - 11:59 PM)	CGM mean glucose mg/dL, daytime only (6:00 AM - 11:59 PM)	15 weeks
Mean Glucose, Nighttime Only (12:00 AM - 5:59 AM)	CGM mean glucose mg/dL, nighttime only (12:00 AM - 5:59 AM)	15 weeks
Coefficient of Variation, Overall	CGM measured Coefficient of Variation, Overall	15 weeks
Coefficient of Variation, Daytime Only (6:00 AM - 11:59 PM)	CGM measured Coefficient of Variation, daytime only (6:00 AM - 11:59 PM)	15 weeks
Coefficient of Variation, Nighttime Only (12:00 AM - 5:59 AM)	CGM measured Coefficient of Variation, nighttime only (12:00 AM - 5:59 AM)	15 weeks
Standard Deviation of All Glucose Values, Overall (24 Hour Day)	CGM measured Standard Deviation of all glucose values (mg/dL), Overall ( 24 Hour Day). Standard Deviation of Mean Glucose is shown separately in Outcome 26.	15 weeks
Standard Deviation of All Glucose Values, Daytime Only (6:00 AM - 11:59 PM)	CGM measured Standard Deviation of all Glucose Values (mg/dL), daytime only (6:00 AM - 11:59 PM). Standard Deviation of Mean Glucose, Daytime only, is shown separately in Outcome 27.	15 weeks
Standard Deviation of All Glucose Values, Nighttime Only (12:00 AM - 5:59 AM)	CGM measured Standard Deviation of all Glucose Values (mg/dL), nighttime only (12:00 AM - 5:59 AM). Standard Deviation of Mean Glucose, Nighttime only, is shown separately in Outcome 28.	15 weeks
Postprandial Percent Time in Range Between 70-180 mg/dL, Through 4 Hours After Each Meal	Postprandial CGM percent time in range between 70-180 mg/dL, through 4 hours after each meal. Calculated as mean (SD) over all 4 hour postprandial periods throughout the study.	during 4 hour postprandial period after each meal, up to 15 weeks
Postprandial Percent Time in Range Between 70-140 mg/dL, Through 4 Hours After Each Meal	Postprandial CGM percent time in range between 70-140 mg/dL, through 4 hours after each meal. Calculated as mean (SD) over all 4 hour postprandial periods throughout the study.	during 4 hour postprandial period after each meal, up to 15 weeks
Postprandial Percent Time Greater Than 180 mg/dL, Through 4 Hours After Each Meal	Postprandial CGM percent time greater than 180 mg/dL, through 4 hours after each meal. Calculated as mean (SD) over all 4 hour postprandial periods throughout the study.	during 4 hour postprandial period after each meal, up to 15 weeks
Postprandial Percent Time Greater Than 250 mg/dL, Through 4 Hours After Each Meal	Postprandial CGM percent time greater than 250 mg/dL, through 4 hours after each meal. Calculated as mean (SD) over all 4 hour postprandial periods throughout the study.	during 4 hour postprandial period after each meal, up to 15 weeks
Peak Postprandial Glucose, Through 4 Hours After Each Meal	Peak postprandial glucose (mg/dL), through 4 hours after each meal. Calculated as mean (SD) over all 4 hour postprandial periods throughout the study.	during 4 hour postprandial period after each meal, up to 15 weeks
Postprandial Mean Glucose, Through 4 Hours After Each Meal	Postprandial CGM mean glucose (mg/dL), through 4 hours after each meal. Calculated as mean (SD) over all 4 hour postprandial periods throughout the study.	during 4 hour postprandial period after each meal, up to 15 weeks
Postprandial Incremental Area Under the Glucose Curve, Through 4 Hours After Each Meal	CGM postprandial incremental area under the glucose curve, through 4 hours after each meal. Calculated as mean (SD) over all 4 hour postprandial periods throughout the study.	during 4 hour postprandial period after each meal, up to 15 weeks
Coefficient of Variation, Postprandial, Through 4 Hours After Each Meal	CGM measured Coefficient of Variation, Postprandial, through 4 hours after each meal. Calculated as mean (SD) over all 4 hour postprandial periods throughout the study.	during 4 hour postprandial period after each meal, up to 15 weeks
Standard Deviation of All Glucose Values, Postprandial Through 4 Hours After Each Meal	CGM measured Standard Deviation of all glucose values (mg/dL), Postprandial through 4 hours after each meal. Calculated as mean (SD) over all 4 hour postprandial periods throughout the study. Standard Deviation of Mean Glucose, Postprandial through 4 hours after each meal, is shown separately in Outcome 40.	during 4 hour postprandial period after each meal, up to 15 weeks
HbA1c Change From Baseline	Change in HbA1c from End of Humalog Lead-in Period (End of Week 2) to End of Lyumjev Treatment Period (End of Week 15)	13 weeks
Patient Reported Outcomes: TRIM-D	Patient Reported Outcomes on the Treatment Related Impact Measure-Diabetes (TRIM-D) scale. Total score measured on a scale of 0 to 100 with higher scores indicating better diabetes treatment impact. Assessed at the start of Humalog Run-In (Start of Week 1) and again at End of Lyumjev use (End of Week 15).	15 weeks
Patient Reported Outcomes: TRIM-DD	Patient Reported Outcomes on the Treatment Related Impact Measure - diabetes device (TRIM-DD) scale. Measured on a scale of 0 to 100 with higher scores indicating more positive diabetes device impact. Assessed at the start of Humalog Run-In (Start of Week 1) and again at End of Lyumjev use (End of Week 15).	15 weeks
Patient Reported Outcomes: ITSQ	Patient Reported Outcomes on the Insulin Treatment Satisfaction Questionnaire (ITSQ) scale. Measured on a scale of 0 to 100 with higher scores indicating better treatment satisfaction. Assessed at the start of Humalog Run-In (Start of Week 1) and again at End of Lyumjev use (End of Week 15).	15 weeks

Collaborators and Investigators

• Sponsor: Tandem Diabetes Care, Inc.
• Collaborators: Eli Lilly and Company; Jaeb Center for Health Research
• Investigators: Study Director: Jordan Pinsker, MD, Tandem Diabetes Care

Publications and helpful links

General Publications

• Levy CJ, Bailey R, Laffel LM, Forlenza G, DiMeglio LA, Hughes MS, Brown SA, Aleppo G, Bhargava A, Shah VN, Clements MA, Kipnes M, Bruggeman B, Daniels M, Rodriguez H, Calhoun P, Lum JW, Sasson-Katchalski R, Pinsker JE, Pollom R, Beck RW; TL1 Study Group. Multicenter Evaluation of Ultra-Rapid Lispro Insulin with Control-IQ Technology in Adults, Adolescents, and Children with Type 1 Diabetes. Diabetes Technol Ther. 2024 May 22. doi: 10.1089/dia.2024.0048. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2022
• Primary Completion (Actual): August 2, 2023
• Study Completion (Actual): August 2, 2023

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: May 31, 2022
• First Posted (Actual): June 3, 2022

Study Record Updates

• Last Update Posted (Actual): July 26, 2024
• Last Update Submitted That Met QC Criteria: July 24, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: type 1 diabetes; Control-IQ Technology; lyumjev
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: TP-0009650

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes