Diabetes Mellitus, Type 1
Conditions
Keywords
Lyumjev, Humalog®, Insulin lispro, Exercise, Continuous Subcutaneous Insulin Infusion, Glycemic control, Hypoglycemia, Type 1 Diabetes
Brief summary
This study will be conducted in participants with type 1 diabetes mellitus on continuous subcutaneous insulin infusion (CSII) or pump therapy to evaluate the effect of LY900014 (Lyumjev) on blood sugar levels during exercise using different approaches on basal rate reduction and following a test meal compared to insulin lispro (Humalog). The study may last up to approximately 10 weeks and may include up to 7 visits.
Interventions
DRUGLyumjev with 50% basal rate reduction
Administered SC.
DRUGHumalog with 50% basal rate reduction
Administered SC.
DRUGHumalog with 100% basal rate reduction
Administered SC.
DRUGLyumjev with 100% basal rate reduction
Administered SC.
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 55 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants with type 1 diabetes * Body mass index (BMI) between 18.5 and 29.0 kilograms per square meter (kg/m²), inclusive * Hemoglobin A1c (HbA1c) less than or equal to 8.5 percent (%) * Using CSII and stable insulin regimen for at least 6 months prior to inclusion into the trial * Able to undergo at least 1 hour of moderate-intensity exercise
Exclusion criteria
* Are currently participating or recently participated in a clinical trial or any other type of medical research judged to be incompatible with this study * Have a blood loss of more than 500 milliliters (mL) within the last month * Have known allergies to insulin lispro, related compounds or any components of the study drug formulation * Have previously participated or withdrawn from this study * Have or used to have health problems or medical test results that, in the opinion of the doctor, could make it unsafe to participate, or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 * Participants who have an abnormal blood pressure and/or pulse rate * Participants with clinically significant cardiac or pulmonary disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD): Change in Plasma Glucose (PG) From the Start to the End of Exercise | Start (0 minute) to end of exercise (60 minutes) | Changes in PG from the start (0 minute) to end of exercise (60 minutes) were analyzed using a mixed-effect model. The model included treatment (Lyumjev with 50% basal reduction, Lyumjev with 100% basal reduction, Humalog with 50% basal reduction, and Humalog with 100% basal reduction), sequence, period, timepoint, treatment-by-timepoint interaction as fixed effects, and participant-within-sequence as a random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Versus Time Curve From Time 0 to 4 Hours [AUC(0-4)] of Postprandial Plasma Glucose (PPG) Post Mixed-Meal Tolerance Test (MMTT) | Baseline (0-hour time point prior of the MMTT), 4 hour post-meal MMTT | The outcome measure was analyzed using a mixed-effect model. The model included treatment (Lyumjev with 50% basal reduction, Lyumjev with 100% basal reduction, Humalog with 50% basal reduction, and Humalog with 100% basal reduction), sequence, and period as fixed effects, and participant-within-sequence will be included as a random effect. |
Countries
Canada
Participant flow
Recruitment details
Participants were randomized to 4 treatment sequences (ADBC, BACD, CBDA, and DCAB), with each sequence having 4 periods where participants were crossed over between the periods. A washout period of at least 3 days was maintained between each treatment period.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants received Lyumjev with 50% basal rate reduction (Treatment A) or Lyumjev with 100% basal rate reduction (Treatment B) or Humalog with 50% basal rate reduction (Treatment C) or Humalog with 100% basal rate reduction (Treatment D) subcutaneously on Day 1 in Treatment Period 1 to 4 as per assigned randomized treatment sequence. A washout period of at least 3 days was maintained between all the treatment periods. | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 36.7 years STANDARD_DEVIATION 10.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 2 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 | 19 Participants |
| Region of Enrollment Canada | 25 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 4 / 25 | 2 / 25 | 3 / 25 | 4 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 | 0 / 25 | 0 / 25 |
Outcome results
Primary
Pharmacodynamics (PD): Change in Plasma Glucose (PG) From the Start to the End of Exercise
Changes in PG from the start (0 minute) to end of exercise (60 minutes) were analyzed using a mixed-effect model. The model included treatment (Lyumjev with 50% basal reduction, Lyumjev with 100% basal reduction, Humalog with 50% basal reduction, and Humalog with 100% basal reduction), sequence, period, timepoint, treatment-by-timepoint interaction as fixed effects, and participant-within-sequence as a random effect.
Time frame: Start (0 minute) to end of exercise (60 minutes)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lyumjev With 50% Basal Rate Reduction | Pharmacodynamics (PD): Change in Plasma Glucose (PG) From the Start to the End of Exercise | -26.8 milligram per Deciliter (mg/dL) | Standard Deviation 37.3 |
| Lyumjev With 100% Basal Rate Reduction | Pharmacodynamics (PD): Change in Plasma Glucose (PG) From the Start to the End of Exercise | -46.9 milligram per Deciliter (mg/dL) | Standard Deviation 31.5 |
| Humalog With 50% Basal Rate Reduction | Pharmacodynamics (PD): Change in Plasma Glucose (PG) From the Start to the End of Exercise | -39.0 milligram per Deciliter (mg/dL) | Standard Deviation 38.8 |
| Humalog With 100% Basal Rate Reduction | Pharmacodynamics (PD): Change in Plasma Glucose (PG) From the Start to the End of Exercise | -60.5 milligram per Deciliter (mg/dL) | Standard Deviation 39.1 |
p-value: 0.049490% CI: [1.52, 17.1]Mixed Models Analysis
p-value: 0.002890% CI: [6.38, 21.9]Mixed Models Analysis
Secondary
Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Versus Time Curve From Time 0 to 4 Hours [AUC(0-4)] of Postprandial Plasma Glucose (PPG) Post Mixed-Meal Tolerance Test (MMTT)
The outcome measure was analyzed using a mixed-effect model. The model included treatment (Lyumjev with 50% basal reduction, Lyumjev with 100% basal reduction, Humalog with 50% basal reduction, and Humalog with 100% basal reduction), sequence, and period as fixed effects, and participant-within-sequence will be included as a random effect.
Time frame: Baseline (0-hour time point prior of the MMTT), 4 hour post-meal MMTT
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lyumjev With 50% Basal Rate Reduction | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Versus Time Curve From Time 0 to 4 Hours [AUC(0-4)] of Postprandial Plasma Glucose (PPG) Post Mixed-Meal Tolerance Test (MMTT) | 247 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 121 |
| Lyumjev With 100% Basal Rate Reduction | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Versus Time Curve From Time 0 to 4 Hours [AUC(0-4)] of Postprandial Plasma Glucose (PPG) Post Mixed-Meal Tolerance Test (MMTT) | 257 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 145 |
| Humalog With 50% Basal Rate Reduction | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Versus Time Curve From Time 0 to 4 Hours [AUC(0-4)] of Postprandial Plasma Glucose (PPG) Post Mixed-Meal Tolerance Test (MMTT) | 202 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 188 |
| Humalog With 100% Basal Rate Reduction | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Versus Time Curve From Time 0 to 4 Hours [AUC(0-4)] of Postprandial Plasma Glucose (PPG) Post Mixed-Meal Tolerance Test (MMTT) | 262 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 129 |
p-value: 0.199890% CI: [-102, 12.8]Mixed Models Analysis
p-value: 0.904190% CI: [-53.1, 61.4]Mixed Models Analysis