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

NCT05067270 | Completed Phase 1 Results

• 3 other identifiers: 18278I8B-MC-ITTC2021-001987-18
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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

Keywords

Humalog - Insulin lispro; Citrate; Infusion Site Pain; Excipients

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (5)

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

EXPERIMENTAL

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; Drug: Treprostinil; Drug: Humalog diluent; Drug: Magnesium Chloride

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

EXPERIMENTAL

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; Drug: Treprostinil; Drug: Humalog diluent; Drug: Magnesium Chloride

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

EXPERIMENTAL

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; Drug: Treprostinil; Drug: Humalog diluent; Drug: Magnesium Chloride

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

EXPERIMENTAL

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; Drug: Treprostinil; Drug: Humalog diluent; Drug: Magnesium Chloride

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

EXPERIMENTAL

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; Drug: Treprostinil; Drug: Humalog diluent; Drug: Magnesium Chloride

Interventions

Sodium Citrate DRUG

Administered SC infusion.

Sequence 1:Arm Region,Abdomen 6mm,Buttock,Abdomen 9mm,Thigh; Sequence 2:Abdomen 6mm,Abdomen 9mm,Arm Region,Thigh,Buttock; Sequence 3:Abdomen 9mm,Thigh,Abdomen 6mm,Buttock,Arm Region; Sequence 4:Thigh,Buttock,Abdomen 9mm,Arm Region,Abdomen 6mm; Sequence 5:Buttock,Arm Region,Thigh,Abdomen 6mm,Abdomen 9mm

Treprostinil DRUG

Administered SC infusion.

Sequence 1:Arm Region,Abdomen 6mm,Buttock,Abdomen 9mm,Thigh; Sequence 2:Abdomen 6mm,Abdomen 9mm,Arm Region,Thigh,Buttock; Sequence 3:Abdomen 9mm,Thigh,Abdomen 6mm,Buttock,Arm Region; Sequence 4:Thigh,Buttock,Abdomen 9mm,Arm Region,Abdomen 6mm; Sequence 5:Buttock,Arm Region,Thigh,Abdomen 6mm,Abdomen 9mm

Humalog diluent DRUG

Administered SC infusion.

Sequence 1:Arm Region,Abdomen 6mm,Buttock,Abdomen 9mm,Thigh; Sequence 2:Abdomen 6mm,Abdomen 9mm,Arm Region,Thigh,Buttock; Sequence 3:Abdomen 9mm,Thigh,Abdomen 6mm,Buttock,Arm Region; Sequence 4:Thigh,Buttock,Abdomen 9mm,Arm Region,Abdomen 6mm; Sequence 5:Buttock,Arm Region,Thigh,Abdomen 6mm,Abdomen 9mm

Magnesium Chloride DRUG

Administered SC infusion.

Sequence 1:Arm Region,Abdomen 6mm,Buttock,Abdomen 9mm,Thigh; Sequence 2:Abdomen 6mm,Abdomen 9mm,Arm Region,Thigh,Buttock; Sequence 3:Abdomen 9mm,Thigh,Abdomen 6mm,Buttock,Arm Region; Sequence 4:Thigh,Buttock,Abdomen 9mm,Arm Region,Abdomen 6mm; Sequence 5:Buttock,Arm Region,Thigh,Abdomen 6mm,Abdomen 9mm

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (2)

Profil Institut für Stoffwechselforschung

Neuss, North Rhine-Westphalia, 41460, Germany

Location

Profil Mainz

Mainz, 55116, Germany

Location

Related Publications (1)

• 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.

  PMID: 36326260 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Sodium Citrate; treprostinil; Magnesium Chloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Citric Acid; Citrates; Tricarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Magnesium Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: October 5, 2021
• Study Start: October 22, 2021
• Primary Completion: December 6, 2021
• Study Completion: December 6, 2021
• Last Updated: October 4, 2023
• Results First Posted: October 4, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)