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

NCT ID: NCT05067270

Last Updated: 2023-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-22
• Study Completion Date: 2021-12-06

Brief Summary

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.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Sequence 1:Arm Region,Abdomen 6mm,Buttock,Abdomen 9mm,Thigh

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.

Group Type: EXPERIMENTAL

Sodium Citrate

Intervention Type: DRUG

Administered SC infusion.

Treprostinil

Intervention Type: DRUG

Administered SC infusion.

Humalog diluent

Intervention Type: DRUG

Administered SC infusion.

Magnesium Chloride

Intervention Type: DRUG

Administered SC infusion.

Sequence 2:Abdomen 6mm,Abdomen 9mm,Arm Region,Thigh,Buttock

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.

Group Type: EXPERIMENTAL

Sodium Citrate

Intervention Type: DRUG

Administered SC infusion.

Treprostinil

Intervention Type: DRUG

Administered SC infusion.

Humalog diluent

Intervention Type: DRUG

Administered SC infusion.

Magnesium Chloride

Intervention Type: DRUG

Administered SC infusion.

Sequence 3:Abdomen 9mm,Thigh,Abdomen 6mm,Buttock,Arm Region

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.

Group Type: EXPERIMENTAL

Sodium Citrate

Intervention Type: DRUG

Administered SC infusion.

Treprostinil

Intervention Type: DRUG

Administered SC infusion.

Humalog diluent

Intervention Type: DRUG

Administered SC infusion.

Magnesium Chloride

Intervention Type: DRUG

Administered SC infusion.

Sequence 4:Thigh,Buttock,Abdomen 9mm,Arm Region,Abdomen 6mm

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.

Group Type: EXPERIMENTAL

Sodium Citrate

Intervention Type: DRUG

Administered SC infusion.

Treprostinil

Intervention Type: DRUG

Administered SC infusion.

Humalog diluent

Intervention Type: DRUG

Administered SC infusion.

Magnesium Chloride

Intervention Type: DRUG

Administered SC infusion.

Sequence 5:Buttock,Arm Region,Thigh,Abdomen 6mm,Abdomen 9mm

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.

Group Type: EXPERIMENTAL

Sodium Citrate

Intervention Type: DRUG

Administered SC infusion.

Treprostinil

Intervention Type: DRUG

Administered SC infusion.

Humalog diluent

Intervention Type: DRUG

Administered SC infusion.

Magnesium Chloride

Intervention Type: DRUG

Administered SC infusion.

Interventions

Sodium Citrate

Administered SC infusion.

Intervention Type: DRUG

Treprostinil

Administered SC infusion.

Intervention Type: DRUG

Humalog diluent

Administered SC infusion.

Intervention Type: DRUG

Magnesium Chloride

Administered SC infusion.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Profil Institut für Stoffwechselforschung

Neuss, North Rhine-Westphalia, Germany

Profil Mainz

Mainz, , Germany

Countries

Germany

References

Ignaut D, Fukuda T, Bandi R, Ermer M, Stoffel MS, Zijlstra E, Paavola C. An Investigation Into Local Infusion Site Pain After Infusion of Ultra Rapid Lispro Excipients Across Sites and Depths. J Diabetes Sci Technol. 2024 Jul;18(4):920-929. doi: 10.1177/19322968221135217. Epub 2022 Nov 3.

Reference Type: DERIVED

PMID: 36326260 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

I8B-MC-ITTC

Identifier Type: OTHER

Identifier Source: secondary_id

2021-001987-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

18278

Identifier Type: -

Identifier Source: org_study_id