Type 1 Diabetes Mellitus
Conditions
Keywords
Humalog - Insulin lispro, Citrate, Infusion Site Pain, Excipients
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.
Interventions
DRUGSodium Citrate
Administered SC infusion.
DRUGTreprostinil
Administered SC infusion.
DRUGHumalog diluent
Administered SC infusion.
Administered SC infusion.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | Day 1: 1 min post bolus. | 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). |
Countries
Germany
Participant flow
Recruitment details
Participants were randomly assigned to 1 of 5 infusion site sequence below and received the study treatment in each period. Cannulas were 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).
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants received 15 mM sodium citrate and 1 μg/mL treprostinil in humalog diluent with 5 mM magnesium chloride (without insulin) as SC infusion.
Six mm cannula was inserted into each of the designated areas (arm, abdomen, thigh, and buttock). At the abdominal area only, a 9 mm cannula was also inserted into the opposite side of the lower abdomen. | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 40.5 years STANDARD_DEVIATION 12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Region of Enrollment Germany | 40 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 | 0 / 40 | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 5 / 40 | 9 / 40 | 4 / 40 | 4 / 40 | 3 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 | 0 / 40 | 0 / 40 | 0 / 40 |
Outcome results
Primary
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).
Time frame: Day 1: 1 min post bolus.
Population: All participants who received at least one infusion and had VAS pain scores.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Given to Arm Region | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 3 hours) | 3.4 millimeter | Geometric Coefficient of Variation 182 |
| Treatment Given to Arm Region | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 9 hours) | 4.8 millimeter | Geometric Coefficient of Variation 211 |
| Treatment Given to Arm Region | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 6 hours) | 3.7 millimeter | Geometric Coefficient of Variation 164 |
| Treatment Given to Thigh | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 6 hours) | 2.6 millimeter | Geometric Coefficient of Variation 137 |
| Treatment Given to Thigh | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 3 hours) | 2.0 millimeter | Geometric Coefficient of Variation 119 |
| Treatment Given to Thigh | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 9 hours) | 3.4 millimeter | Geometric Coefficient of Variation 155 |
| Treatment Given to Abdomen (6 mm) | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 6 hours) | 2.3 millimeter | Geometric Coefficient of Variation 151 |
| Treatment Given to Abdomen (6 mm) | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 3 hours) | 1.8 millimeter | Geometric Coefficient of Variation 112 |
| Treatment Given to Abdomen (6 mm) | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 9 hours) | 2.5 millimeter | Geometric Coefficient of Variation 141 |
| Treatment Given to Abdomen (9 mm) | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 3 hours) | 1.9 millimeter | Geometric Coefficient of Variation 119 |
| Treatment Given to Abdomen (9 mm) | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 9 hours) | 2.4 millimeter | Geometric Coefficient of Variation 141 |
| Treatment Given to Abdomen (9 mm) | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 6 hours) | 2.0 millimeter | Geometric Coefficient of Variation 113 |
| Treatment Given to Buttock | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 6 hours) | 3.3 millimeter | Geometric Coefficient of Variation 161 |
| Treatment Given to Buttock | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 3 hours) | 2.4 millimeter | Geometric Coefficient of Variation 167 |
| Treatment Given to Buttock | Visual Analog Scale (VAS) Pain Score in the Abdominal, Arm, Thigh, and Buttock Areas | 1 min post bolus (Bolus time: 9 hours) | 3.8 millimeter | Geometric Coefficient of Variation 196 |
Comparison: 1 min post bolus (Bolus time: 3 hours)95% CI: [1.3, 2.4]
Comparison: 1 min post bolus (Bolus time: 3 hours)95% CI: [1.42, 2.59]
Comparison: 1 min post bolus (Bolus time: 3 hours)95% CI: [1.37, 2.49]
Comparison: 1 min post bolus (Bolus time: 3 hours)95% CI: [1.05, 1.92]
Comparison: 1 min post bolus (Bolus time: 3 hours)95% CI: [0.8, 1.46]
Comparison: 1 min post bolus (Bolus time: 3 hours)95% CI: [0.77, 1.41]
Comparison: 1 min post bolus (Bolus time: 3 hours)95% CI: [0.59, 1.08]
Comparison: 1 min post bolus (Bolus time: 3 hours)95% CI: [0.72, 1.3]
Comparison: 1 min post bolus (Bolus time: 3 hours)95% CI: [0.55, 1]
Comparison: 1 min post bolus (Bolus time: 9 hours)95% CI: [1.5, 2.74]
Comparison: 1 min post bolus (Bolus time: 3 hours)95% CI: [0.57, 1.04]
Comparison: 1 min post bolus (Bolus time: 6 hours)95% CI: [1.09, 2.02]
Comparison: 1 min post bolus (Bolus time: 6 hours)95% CI: [1.25, 2.28]
Comparison: 1 min post bolus (Bolus time: 6 hours)95% CI: [1.36, 2.48]
Comparison: 1 min post bolus (Bolus time: 6 hours)95% CI: [0.85, 1.56]
Comparison: 1 min post bolus (Bolus time: 6 hours)95% CI: [0.83, 1.54]
Comparison: 1 min post bolus (Bolus time: 6 hours)95% CI: [0.91, 1.68]
Comparison: 1 min post bolus (Bolus time: 6 hours)95% CI: [0.57, 1.05]
Comparison: 1 min post bolus (Bolus time: 6 hours)95% CI: [0.81, 1.47]
Comparison: 1 min post bolus (Bolus time: 6 hours)95% CI: [0.51, 0.93]
Comparison: 1 min post bolus (Bolus time: 6 hours)95% CI: [0.47, 0.85]
Comparison: 1 min post bolus (Bolus time: 9 hours)95% CI: [1.1, 2.03]
Comparison: 1 min post bolus (Bolus time: 9 hours)95% CI: [1.45, 2.65]
Comparison: 1 min post bolus (Bolus time: 9 hours)95% CI: [0.93, 1.69]
Comparison: 1 min post bolus (Bolus time: 9 hours)95% CI: [0.97, 1.78]
Comparison: 1 min post bolus (Bolus time: 9 hours)95% CI: [1.01, 1.84]
Comparison: 1 min post bolus (Bolus time: 9 hours)95% CI: [0.62, 1.14]
Comparison: 1 min post bolus (Bolus time: 9 hours)95% CI: [0.77, 1.4]
Comparison: 1 min post bolus (Bolus time: 9 hours)95% CI: [0.47, 0.86]
Comparison: 1 min post bolus (Bolus time: 9 hours)95% CI: [0.46, 0.83]