Pharmacokinetics (PK)/ Pharmacodynamics (PD) of an Extended Wear Infusion Set for Continuous Subcutaneous Insulin Infusion (CSII) in Type 1 Diabetes Mellitus (T1DM) Patients (PEXIS)

Study Overview
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Brief Summary
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This study has been designed as a prospectively enrolled, randomized sequence, 2-way crossover study of device performance, tolerability and safety of an investigational insulin infusion set using a coil-reinforced soft polymer indwelling cannula versus a commercial insulin infusion set using a soft Teflon indwelling cannula, during two 7-day home use periods with 4 in-clinic euglycemic clamp sessions during each of the 7-day periods. After a wash-out period, subjects will cross over into the investigational or control group, respectively.

Official Title
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Randomized Crossover Euglycemic Clamp Study in Adult Patients With T1DM to Assess Pharmacokinetics and Pharmacodynamics of Subcutaneously Infused Insulin Using an Investigational Extended Wear Continuous Subcutaneous Insulin Infusion Cannula Compared to a Commercial Infusion Set

Conditions
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Diabetes Mellitus, Type 1, Type 1 Diabetes

Intervention / Treatment
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* Device: coil-reinforced soft polymer indwelling cannula
* Device: soft Teflon indwelling catheter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet all of the following criteria: Participants are 18 - 70 years of age inclusive Participant is in generally good health, as determined by the investigator Participant is willing and able to individually complete written informed consent and agrees to comply with all study related testing and examinations Participant must be geographically stable (e.g., expects to be available and capable of returning for all study specified test and examinations) during the study period Participant has been diagnosed with T1DM for at least 12 months C-peptide <0.6 nmol/L at screening Participant has been using insulin pump therapy for at least 6 months and is currently using a Medtronic MiniMed pump, model series 530 or higher. Use of 670G in auto mode is acceptable. Participant can provide a minimum of 14 days of insulin pump data to demonstrate pump use compliance Participant is willing to perform frequent (4 times per day or more) self-monitoring of blood glucose (SMBG), including before meals and before bed, and using a meter and test strips provided by the sponsor during the two weeks of active treatment. This includes participants who are currently using real-time continuous glucose monitoring and may continue to do so, but must also collect SMBG values as instructed. Participant is willing to perform serum ketone measurements whenever the blood glucose is determined to be greater than 250 mg/dL after extended fasting (e.g. overnight or more than five hours after a meal) using a ketone meter and strips provided by the sponsor Participant has BMI in the range 20 - 35 kg/m2 inclusive Participant has experience infusing a rapid-acting insulin analog for at least 6 months Participant has been using or is willing to use a Continuous Glucose Monitor (CGM) (reading data available for at least 80% of time for a week of data collection during the screening period). Participants already using - Dexcom G6 real time CGM may continue to use their own CGM unit; participants not using the G6 will be provided with a G6 monitor. All participants will be provided with CGM disposables for use during the treatment period. Participant has ability to understand and comply with protocol procedures and to provide informed consent HbA1c ≤8.5% Stable body weight in the 3 months prior to enrollment (change in body weight <5%) Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: Participants whose average total daily insulin dose exceeds 85 units/day (i.e., typically change insulin reservoirs more often than every 4 days on average) Participants who routinely change their commercial insulin infusion sets on average less often than every 4.5 days Female participant is pregnant or nursing Participant has abnormal skin at intended device infusion sites (existing infection, inflammation, burns, or other extensive scarring) Participant has hemoglobin <12.0 g/dL or potassium < 3.5 milliequivalent/L at screening Participant has documented history in last 6 months of severe hypoglycemia associated with cognitive dysfunction sufficiently severe to require third party intervention or a history of impaired awareness of hypoglycemia. Participant has a history of diabetic ketoacidosis in the last 6 months Participant has known cardiovascular disease considered to be clinically relevant by the investigator Participant has known arrhythmias considered to be clinically relevant by the investigator Participant has known history of: Cushing's Disease, Pancreatic islet cell tumor, or Insulinoma Participant has: Lipodystrophy, Extensive lipohypertrophy, as assessed by the investigator Participant is undergoing current treatment with: Systemic oral or intravenous corticosteroids, Monoamine oxidase (MAO) inhibitors, Non-selective systemic beta-blockers, Growth hormone, Thyroid hormones, unless use has been stable during the past 3 months SGLT2 inhibitors Participant has significant history of any of the following, that in the opinion of the investigator would compromise the participant's safety or successful study participation: Alcoholism, Drug abuse Significant acute or chronic illness, that in the investigator's opinion, might interfere with participant safety or integrity of study results Planned operation, MRI or CT which require removal of infusion set or CGM sensor during wear periods Current treatment with systemic (oral or IV) corticosteroids, monoamine oxidase (MAO) inhibitors, non-selective beta-blockers, growth hormone, herbal products that, in the opinion of the investigator, may alter insulin sensitivity or confer undue risk to the participant's participation in the study or non-routine vitamins. Furthermore, thyroid hormones are not allowed unless the use of these has been stable during the past 3 months. Current participation in another clinical drug or device study Inability of the participant to comply with all study procedures or to understand the participant instructions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: coil-reinforced soft polymer indwelling cannula<br>Participants in this arm are randomized into the coil-reinforced soft polymer indwelling cannula group and then switched to a soft Teflon indwelling cannula group after a 2-week washout/rest (±1 week). The participant will try to wear each infusion set for 7 consecutive days. | Device: coil-reinforced soft polymer indwelling cannula<br>* Insulin infusion set will be used for up to 7 days of continuous use or until failure<br>|
| Active Comparator: soft Teflon indwelling cannula<br>Participants in this arm are randomized into the soft Teflon indwelling cannula group and then switched to the coil-reinforced soft polymer indwelling cannula group after a 2-week washout/rest (±1 week). The participant will try to wear each infusion set for 7 consecutive days. | Device: soft Teflon indwelling catheter<br>* Insulin infusion set will be used for up to 7 days of continuous use or until failure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Endpoint is the Rate of Decline (s) Over Wear Time (DOI, Day 3, Day 5, Day 7) of the Natural Logarithm of the Area Under the Glucose Infusion Rate Curve [ln (AUC0-300(GIR))]. | The primary endpoint will be compared between the treatment groups. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-Maximum Insulin Concentration (Tmax) | The Time-to-Maximum Glucose Infusion (GIR) rate, tmax (GIR) is the minute between the time corresponding to the GIR max and Time 0. | 7 days | 
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Maximum Insulin Concentration (Cmax) | Cmax is the maximum insulin concentration between t=0 (bolus) and t=300 minutes. | 7 days | 
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Early) Maximum Insulin Concentration [t50%(Early)] | The time to half-maximal insulin concentration- early (before peak) | 7 days | 
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Mean-residence Time (MRT) of Insulin | Mean residence time quantifies the sum of average absorption time and average systemic residence time. | 7 days | 
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Area Under the Curve (AUC0-300) | The area under the insulin concentration curve until 300 minutes after bolus administration | 7 days | 
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Insulin Early Exposure: AUC0-60 | Area under the insulin concentration curve in the first 60 minutes after bolus administration | 7 days | 
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Late) Maximum Insulin Concentration [t50%(Late)] | Time at which 50% of the maximum insulin concentration was reached. | 7 days |