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

• ClinicalTrials.gov Identifier: NCT05403502
• Recruitment Status: Completed
• First Posted: June 3, 2022
• Last Update Posted: August 7, 2023
• Sponsor: Tandem Diabetes Care, Inc.
• Collaborators: Eli Lilly and Company; Jaeb Center for Health Research
• Information provided by (Responsible Party): Tandem Diabetes Care, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Device: t:slim X2 insulin pump with Control-IQ technology 1.5	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 183 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 31, 2022
• Actual Primary Completion Date: August 2, 2023
• Actual Study Completion Date: August 2, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Severe hypoglycemia [ Time Frame: 3 months ]
   Number of severe hypoglycemia events (with cognitive impairment such that assistance of another individual is needed for treatment) during study compared with data on severe hypoglycemic events reported by T1D Exchange clinic registry
2. Diabetic ketoacidosis [ Time Frame: 3 months ]
   Number of diabetic ketoacidosis events
3. Unanticipated adverse device effects [ Time Frame: 3 months ]
   Number of unanticipated adverse device effects (UADE) events
4. Other serious adverse events [ Time Frame: 3 months ]
   Number of other serious adverse events
5. Adverse drug reactions [ Time Frame: 3 months ]
   Number of adverse drug reactions

Secondary Outcome Measures :

1. All reportable adverse events [ Time Frame: 3 months ]
   Number of reportable adverse events during the course of the study
2. CGM hypoglycemia outcomes: Overall % time <54 mg/dL [ Time Frame: 3 months ]
   CGM overall percent time < 54 mg/dL
3. CGM hypoglycemia outcomes: Postprandial % time <54 mg/dL [ Time Frame: 3 months ]
   CGM postprandial percent time < 54 mg/dL
4. CGM hypoglycemia outcomes: Overall % time <70 mg/dL [ Time Frame: 3 months ]
   CGM overall percent time < 70 mg/dL
5. CGM hypoglycemia outcomes: Postprandial % time <70 mg/dL [ Time Frame: 3 months ]
   CGM postprandial percent time < 70 mg/dL
6. CGM hypoglycemia outcomes: Rate of hypoglycemia events [ Time Frame: 3 months ]
   Rate of hypoglycemia events defined as 15 or more consecutive minutes <54 mg/dL

Other Outcome Measures:

1. Postprandial incremental area under the glucose curve [ Time Frame: 4 hours ]
   CGM postprandial incremental area under the glucose curve (4 hr)
2. Peak postprandial glucose [ Time Frame: 4 hours ]
   Peak postprandial glucose (mg/dL)
3. Time in range - overall and postprandial 70-180 mg/dL [ Time Frame: 3 months ]
   CGM time in range 70-180 mg/dL overall and postprandial
4. Time in range - overall and postprandial >180 mg/dL [ Time Frame: 3 months ]
   CGM time in range >180 mg/dL overall and postprandial
5. Time in range - overall and postprandial >250 mg/dL [ Time Frame: 3 months ]
   CGM time in range >250 mg/dL overall and postprandial
6. Times in range - overall and postprandial 70-140 mg/dL [ Time Frame: 3 months ]
   CGM time in range 70-140 mg/dL overall and postprandial
7. Mean glucose [ Time Frame: 3 months ]
   Mean CGM glucose mg/dL
8. Rate of hyperglycemia events [ Time Frame: 3 months ]
   Rate of hyperglycemia events, defined as 90 or more minutes >300 mg/dL within 120 minutes
9. Overall variability (Coefficient of Variation and Standard Deviation) [ Time Frame: 3 months ]
   CGM overall variability as measured by Coefficient of Variation and Standard Deviation (mg/dL)
10. HbA1c change from baseline [ Time Frame: 3 months ]
    Change in HbA1c (%) from baseline to 3 months
11. CGM metrics for time in range by time of day [ Time Frame: 3 months ]
    CGM metrics for time in range for: All 24 hours of the day, Daytime only (06:00AM to 00:00AM), Nighttime only (00:00AM to 06:00AM).
12. CGM metrics for time in hypoglycemia by time of day [ Time Frame: 3 months ]
    CGM metrics for time in hypoglycemia for: All 24 hours of the day, Daytime only (06:00AM to 00:00AM), Nighttime only (00:00AM to 06:00AM).
13. CGM metrics for time in hyperglycemia by time of day [ Time Frame: 3 months ]
    CGM metrics for time in hyperglycemia for: All 24 hours of the day, Daytime only (06:00AM to 00:00AM), Nighttime only (00:00AM to 06:00AM).
14. CGM metrics for glucose variability by time of day [ Time Frame: 3 months ]
    CGM metrics for glucose variability for: All 24 hours of the day, Daytime only (06:00AM to 00:00AM), Nighttime only (00:00AM to 06:00AM).
15. Patient Reported Outcomes: TRIM-D [ Time Frame: 3 months ]
    Patient Reported Outcomes on the TRIM-D scale, comparing baseline to 3 months
16. Patient Reported Outcomes: TRIM-DD [ Time Frame: 3 months ]
    Patient Reported Outcomes on the TRIM-DD scale, comparing baseline to 3 months
17. Patient Reported Outcomes: ITSQ [ Time Frame: 3 months ]
    Patient Reported Outcomes on the ITSQ scale, comparing baseline to 3 months

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Children's Hospital Orange County

Orange, California, United States, 92868

Stanford University

Palo Alto, California, United States, 94304

United States, Colorado

Barbara Davis Center

Aurora, Colorado, United States, 80045

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

University of South Florida Diabetes Center

Tampa, Florida, United States, 33612

United States, Illinois

Northwestern University

Evanston, Illinois, United States, 60208

United States, Indiana

Indiana University / Riley Hospital for Children

Indianapolis, Indiana, United States, 46202

United States, Iowa

Iowa Diabetes and Endocrinology Research Center (IDERC)

West Des Moines, Iowa, United States, 50265

United States, Massachusetts

Joslin Diabetes Center

Boston, Massachusetts, United States, 02215

United States, Missouri

Children's Mercy Hospital

Kansas City, Missouri, United States, 64108

United States, New York

Icahn School of Medicine at Mt. Sinai

New York, New York, United States, 10029

United States, Texas

Diabetes & Glandular Disease (DGD)

San Antonio, Texas, United States, 78229

United States, Virginia

University of Virginia

Charlottesville, Virginia, United States, 22903

Sponsors and Collaborators

Tandem Diabetes Care, Inc.

Eli Lilly and Company

Jaeb Center for Health Research

Investigators

• Study Director: Jordan Pinsker, MD; Tandem Diabetes Care

More Information

• Responsible Party: Tandem Diabetes Care, Inc.
• ClinicalTrials.gov Identifier: NCT05403502
• Other Study ID Numbers: TP-0009650
• First Posted: June 3, 2022
• Last Update Posted: August 7, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Tandem Diabetes Care, Inc.:

type 1 diabetes; Control-IQ Technology; lyumjev

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Insulin; Hypoglycemic Agents; Physiological Effects of Drugs