A Study of Infusion Site Pain After Infusion of Excipients in Participants With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the effect of excipients sodium citrate and treprostinil without insulin on local infusion site pain in participants with type 1 diabetes mellitus (T1DM) on continuous subcutaneous insulin infusion (CSII). The study may last up to 36 days including a screening period and 3 visits.

Official Title
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A Study to Investigate Local Infusion Site Pain After Infusion of Excipients Across Infusion Sites and Infusion Depths

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sodium Citrate
* Drug: Treprostinil
* Drug: Humalog diluent
* Drug: Magnesium Chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T1D for at least 1 year and continuously using insulin for at least 1 year Using an insulin pump for at least the last 6 months Have hemoglobin A1c (HbA1c) value of ≤ 9.0% Have a body mass index (BMI) within the range of 18.5 to 35.0 kilograms per square meter (kg/m²) Have medical and laboratory test results that are acceptable for the study Have venous access sufficient to allow for blood sampling Exclusion Criteria: Hemophilia or any other bleeding disorder Have a pathologic tuning fork test as assessed with a Rydel-Seiffer tuning fork Are taking anesthetics or pain medication regularly or intermittently which could interfere with interpretation of pain scale Have had more than 1 episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within the last 90 days prior to screening Have had more than 1 emergency room visit or hospitalization due to poor glucose control (hyperglycemia or diabetic ketoacidosis) within the last 6 months prior to screening Have any hypersensitivity or allergy to any of the diluents or excipients used in this trial Have or used to have health problems or medical test results that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study Have participated, within the last 30 days, in a clinical trial involving an investigational product Have used or are currently using Lyumjev® as part of their standard insulin therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1:Arm Region,Abdomen 6mm,Buttock,Abdomen 9mm,Thigh<br>Participants had cannulas inserted into each of the designated infusion sites (6 millimeter (mm) for all the sites. Additionally for the abdominal area only, a 9 mm cannula was also inserted into the opposite side of the lower abdomen), and the first infusion site was initiated subcutaneously (SC) with 15 millimolar (mM) sodium citrate and 1 microgram per milliliter (μg/mL) treprostinil in Humalog diluent with 5 mM magnesium chloride (without insulin) solution at a basal infusion rate of 1 unit per hour (U/h). The same procedure occurred at subsequent infusion sites with an approximately 30-minute (min) interval between each initiation. Approximately 3, 6, and 9 hours after the start of the basal infusion, a bolus dose of 15 U was delivered at quick bolus speed (15 U/min) to each infusion site according to the treatment sequence with an approximately 30-minute interval between infusion sites. | Drug: Sodium Citrate<br>* Administered SC infusion.<br>Drug: Treprostinil<br>* Administered SC infusion.<br>Drug: Humalog diluent<br>* Administered SC infusion.<br>Drug: Magnesium Chloride<br>* Administered SC infusion.<br>|
| Experimental: Sequence 2:Abdomen 6mm,Abdomen 9mm,Arm Region,Thigh,Buttock<br>Participants had cannulas inserted into each of the designated infusion sites (6 mm for all the sites. Additionally for the abdominal area only, a 9 mm cannula was also inserted into the opposite side of the lower abdomen), and the first infusion site was initiated with 15 mM sodium citrate and 1 μg/mL treprostinil in Humalog diluent with 5 mM magnesium chloride (without insulin) solution at a basal infusion rate of 1 U/h. The same procedure occurred at subsequent infusion sites with an approximately 30-minute interval between each initiation. Approximately 3, 6, and 9 hours after the start of the basal infusion, a bolus dose of 15 U was delivered at quick bolus speed (15 U/min) to each infusion site according to the treatment sequence with an approximately 30-minute interval between infusion sites. | Drug: Sodium Citrate<br>* Administered SC infusion.<br>Drug: Treprostinil<br>* Administered SC infusion.<br>Drug: Humalog diluent<br>* Administered SC infusion.<br>Drug: Magnesium Chloride<br>* Administered SC infusion.<br>|
| Experimental: Sequence 3:Abdomen 9mm,Thigh,Abdomen 6mm,Buttock,Arm Region<br>Participants had cannulas inserted into each of the designated infusion sites (6 mm for all the sites. Additionally for the abdominal area only, a 9 mm cannula was also inserted into the opposite side of the lower abdomen), and the first infusion site was initiated with 15 mM sodium citrate and 1 μg/mL treprostinil in Humalog diluent with 5 mM magnesium chloride (without insulin) solution at a basal infusion rate of 1 U/h. The same procedure occurred at subsequent infusion sites with an approximately 30-minute interval between each initiation. Approximately 3, 6, and 9 hours after the start of the basal infusion, a bolus dose of 15 U was delivered at quick bolus speed (15 U/min) to each infusion site according to the treatment sequence with an approximately 30-minute interval between infusion sites. | Drug: Sodium Citrate<br>* Administered SC infusion.<br>Drug: Treprostinil<br>* Administered SC infusion.<br>Drug: Humalog diluent<br>* Administered SC infusion.<br>Drug: Magnesium Chloride<br>* Administered SC infusion.<br>|
| Experimental: Sequence 4:Thigh,Buttock,Abdomen 9mm,Arm Region,Abdomen 6mm<br>Participants had cannulas inserted into each of the designated infusion sites (6 mm for all the sites. Additionally for the abdominal area only, a 9 mm cannula was also inserted into the opposite side of the lower abdomen), and the first infusion site was initiated with 15 mM sodium citrate and 1 μg/mL treprostinil in Humalog diluent with 5 mM magnesium chloride (without insulin) solution at a basal infusion rate of 1 units per U/h. The same procedure occurred at subsequent infusion sites with an approximately 30-minute interval between each initiation. Approximately 3, 6, and 9 hours after the start of the basal infusion, a bolus dose of 15 U was delivered at quick bolus speed (15 U/min) to each infusion site according to the treatment sequence with an approximately 30-minute interval between infusion sites. | Drug: Sodium Citrate<br>* Administered SC infusion.<br>Drug: Treprostinil<br>* Administered SC infusion.<br>Drug: Humalog diluent<br>* Administered SC infusion.<br>Drug: Magnesium Chloride<br>* Administered SC infusion.<br>|
| Experimental: Sequence 5:Buttock,Arm Region,Thigh,Abdomen 6mm,Abdomen 9mm<br>Participants had cannulas inserted into each of the designated infusion sites (6 mm for all the sites. Additionally for the abdominal area only, a 9 mm cannula was also inserted into the opposite side of the lower abdomen), and the first infusion site was initiated with 15 mM sodium citrate and 1 μg/mL treprostinil in Humalog diluent with 5 mM magnesium chloride (without insulin) solution at a basal infusion rate of 1 U/h. The same procedure occurred at subsequent infusion sites with an approximately 30-minute interval between each initiation. Approximately 3, 6, and 9 hours after the start of the basal infusion, a bolus dose of 15 U was delivered at quick bolus speed (15 U/min) to each infusion site according to the treatment sequence with an approximately 30-minute interval between infusion sites. | Drug: Sodium Citrate<br>* Administered SC infusion.<br>Drug: Treprostinil<br>* Administered SC infusion.<br>Drug: Humalog diluent<br>* Administered SC infusion.<br>Drug: Magnesium Chloride<br>* Administered SC infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | The Infusion site pain VAS score is a participant administered single item scale designed to measure pain using a 0-100 millimeter (mm) horizontal VAS. Overall severity of participant's pain is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (worst imaginable pain). | Day 1: 1 min post bolus. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Humalog - Insulin lispro, Citrate, Infusion Site Pain, Excipients