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The main objective is to determine the efficacy of Lyumjev (insulin) in a bi-hormonal reactive closed loop system for automated glucose regulation (artificial pancreas; AP®) in patients with diabetes mellitus type 1. In addition, safety parameters, pharmacodynamics and AP-related parameters will be acquired.
This study is a multicenter, open-label, randomized, cross-over trial in 12 subjects. The subjects will be randomized to receive either Lyumjev or Humalog® for a 30-day study period and will then switch to the alternate insulin treatment after a wash-out period.
Background of the study:
Inreda Diabetic B.V. (Goor, The Netherlands) developed a bi-hormonal reactive closed loop system to automate glucose regulation (artificial pancreas; AP) in patients with diabetes mellitus type 1. In the current CE-marked AP, Humalog® (Eli Lilly) is used as rapid-acting insulin. Currently, the ultra rapid-acting insulin Lyumjev (Eli Lilly) is available but has not yet been tested in combination with the AP of Inreda. Both are insulin lispro, but additions to the insulin lispro allow the insulin to act faster with a shorter duration. The hypothesis is that the combination of Lyumjev and the reactive AP system can decrease the time that glucose values are above range which can have a positive effect on glucose regulation.
Objectives of the study:
The main objective is to determine the efficacy of Lyumjev in the Inreda AP system. Secondary objectives are to assess safety parameters, differences in pharmacodynamics and AP-related outcomes comparing Lyumjev to Humalog®.
Study design:
This study is a multicenter, open-label, randomized, cross-over trial which will be performed in a free-living environment.
Study population:
The study population will comprise 12 subjects with diabetes type 1 using the AP system. Inclusion criteria are subjects from 18 to 75 years and treated with the Inreda AP system for at least 1 month.
Intervention:
The intervention includes the administration of Lyumjev by the Inreda AP system. The subject will be randomized to receive either Lyumjev or Humalog® during the first 30 days. After a wash-out period of 8 days using the standard insulin Humalog®, the subject will switch to the alternate treatment, again for a 30-day period. During the study periods, subjects have to keep a Wi-Fi access point with them.
Primary study parameters/outcome of the study:
Main parameter to express efficacy is the time above range (>10.0 mmol/l), which will be compared between Lyumjev and Humalog®.
Secondary study parameters/outcome of the study:
Safety will be expressed as the side effects of Lyumjev. Pharmacodynamics will be expressed in proportions of time spent in eu-/hypo-/hyperglycemia (%), median glucose value (mmol/l) and glycemic variability (% and interquartile range). These parameters will all be compared between Lyumjev and reference Humalog®.
AP-related outcomes will be expressed in daily administered dosage of insulin and glucagon (units), and the percentage of time that the closed loop algorithm is active (%).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lyumjev (insulin lispro) | Experimental | Administration of Lyumjev for a 30-day study period (dosage and frequency is patient-dependent) |
|
| Humalog (insulin lispro) | Active Comparator | Administration of standard used Humalog for a 30-day study period and 8-day wash-out period located between the two study periods (dosage and frequency is patient-dependent) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Insulin Lispro Cartridge [Lyumjev] | Drug | Administration of Lyumjev in combination with the AP system |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Time the Glucose Level is Above 10 mmol/l | Time the glucose level is above range (>10 mmol/l) expressed as a percentage (%) | 25 days for each intervention period (50 days in total); 5-day training period and washout period were excluded from analysis; data were continuously acquired |
| Measure | Description | Time Frame |
|---|---|---|
| Side Effects of Insulin | Side effects of insulin (each reported side effect of Humalog and Lyumjev) | 68 days (whole study period) |
| Pharmacodynamic Parameters: Euglycemia | Percentage of time the glucose level is between 3.9 and 10 mmol/l (%) |
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Inclusion Criteria:
Since subjects are treated with the Inreda AP, the following inclusion criteria will be met:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| A. van Bon, MD, PhD | Rijnstate Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rijnstate Hospital | Arnhem | Gelderland | 6815 AD | Netherlands | ||
| Slingeland Hospital |
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| ID | Title | Description |
|---|---|---|
| FG000 | Lyumjev-Humalog (Insulin Lispro) Sequence | Administration of Lyumjev for a 30-day study period (dosage and frequency is patient-dependent) Insulin Lispro Cartridge [Lyumjev]: Administration of Lyumjev in combination with the AP system |
| FG001 | Humalog-Lyumjev (Insulin Lispro) Sequence | Administration of standard used Humalog for a 30-day study period and 8-day wash-out period located between the two study periods (dosage and frequency is patient-dependent) Insulin Lispro Cartridge: Administration of Humalog in combination with the AP system (standard therapy) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Humalog or Lyumjev (Insulin Lispro) | Administration of Humalog or Lyumjev(cross-over design) for a 30-day study period with a 8-day wash-out period between the two study periods (dosage and frequency is patient-dependent) Insulin Lispro Cartridge: Administration of Humalog in combination with the AP system (standard therapy) Insulin Lispro Cartridge [Lyumjev]: Administration of Lyumjev in combination with the AP system |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Time the Glucose Level is Above 10 mmol/l | Time the glucose level is above range (>10 mmol/l) expressed as a percentage (%) | AP settings for standard treatment (Humalog) were already optimal as a result of long term regular care. However, in the Lyumjev-Humalog sequence, these optimal AP settings were not set again when starting with Humalog. Instead, optimized settings for Lyumjev were used. This procedural error with an unknown influence on glucose regulation rendered a reliable cross-over comparison impossible, which required exclusion of the AP data from these five participants before data analysis. | Posted | Mean | Standard Deviation | percentage of time spent above range | 25 days for each intervention period (50 days in total); 5-day training period and washout period were excluded from analysis; data were continuously acquired |
|
30 days for each intervention period; a total of 68 days including 8-day washout period
Adverse events for all twelve participants are listed, while glucose data of 7 of 12 participants are included in the data analysis (because of an error).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lyumjev (Insulin Lispro) | Use of Lyumjev (during both sequences) | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Side effects of infusion sets | Skin and subcutaneous tissue disorders | Systematic Assessment |
AP settings for standard treatment (Humalog) were already optimal as a result of long term regular care. However, in the Lyumjev-Humalog sequence, these optimal AP settings were not set again when starting with Humalog. Instead, optimized settings for Lyumjev were used. This procedural error with an unknown influence on glucose regulation rendered a reliable cross-over comparison impossible, which required the exclusion of AP data from these five participants before data analysis.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Projects Specialist | Inreda Diabetic B.V. | 0031547262628 | tom.jansen@inredadiabetic.nl |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 16, 2022 | Dec 10, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 1, 2025 | Dec 17, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D061268 | Insulin Lispro |
| ID | Term |
|---|---|
| D061266 | Insulin, Short-Acting |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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Allocation by randomization:
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| Insulin Lispro Cartridge | Drug | Administration of Humalog in combination with the AP system (standard therapy) |
|
|
| 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
| Pharmacodynamic Parameters: Hypoglycemia | Percentage of time the glucose level is below 3.9 mmol/l (%) | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
| Pharmacodynamic Parameters: Mean Glucose Value | Mean of the glucose values (parameter required to determine the coefficient of variation) | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
| Pharmacodynamic Parameters: Standard Deviation of Glucose Value | Standard deviation of the glucose values (parameter required to determine the coefficient of variation) | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
| Pharmacodynamic Parameters: Glycemic Variability (CoV) | Glycemic variability expressed as the coefficient of variation (CoV): standard deviation divided by the mean of the glucose values (%) | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
| Pharmacodynamic Parameters: Glycemic Variability (IQR) | Glycemic variability expressed as the interquartile range (IQR) (mmol/l) | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
| AP-related Parameters: Daily Insulin Usage (Units) | Daily insulin usage (units) | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
| AP-related Parameters: Glucagon Usage | Daily usage of glucagon (mg) | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
| AP-related Parameters: Algorithm Activity | Percentage of time the algorithm is active (%) | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
| Doetinchem |
| Gelderland |
| 7009 BL |
| Netherlands |
| Hospital Gelderse Vallei | Ede | Gelderland | 6716 RP | Netherlands |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | Participants |
|
| Diabetes duration | Because only the Humalog-Lyumjev sequence was included in the analysis | Median | Inter-Quartile Range | years |
|
| HbA1c | Because only the Humalog-Lyumjev sequence was included in the analysis | Median | Inter-Quartile Range | mmol/mol |
|
| BMI | Because only the Humalog-Lyumjev sequence was included in the analysis | Mean | Standard Deviation | kg/m^2 |
|
Administration of Lyumjev for a 30-day study period, 8-day wash-out period, and then standard used Humalog for a 30-day study period (dosage and frequency is patient-dependent)
Insulin Lispro Cartridge: Administration of Humalog in combination with the AP system (standard therapy) Insulin Lispro Cartridge [Lyumjev]: Administration of Lyumjev in combination with the AP system
| OG001 | Lyumjev-Humalog (Insulin Lispro) Sequence (Humalog Period) | Administration of standard used Humalog for a 30-day study period, 8-day wash-out period, and then Lyumjev for a 30-day study period (dosage and frequency is patient-dependent) Insulin Lispro Cartridge: Administration of Humalog in combination with the AP system (standard therapy) Insulin Lispro Cartridge [Lyumjev]: Administration of Lyumjev in combination with the AP system |
| OG002 | Humalog-Lyumjev (Insulin Lispro) Sequence (Humalog Period) | Administration of standard used Humalog for a 30-day study period, 8-day wash-out period, and then Lyumjev for a 30-day study period (dosage and frequency is patient-dependent) Insulin Lispro Cartridge: Administration of Humalog in combination with the AP system (standard therapy) Insulin Lispro Cartridge [Lyumjev]: Administration of Lyumjev in combination with the AP system |
| OG003 | Humalog-Lyumjev (Insulin Lispro) Sequence (Lyumjev Period) | Administration of standard used Humalog for a 30-day study period, 8-day wash-out period, and then Lyumjev for a 30-day study period (dosage and frequency is patient-dependent) Insulin Lispro Cartridge: Administration of Humalog in combination with the AP system (standard therapy) Insulin Lispro Cartridge [Lyumjev]: Administration of Lyumjev in combination with the AP system |
|
|
| Secondary | Side Effects of Insulin | Side effects of insulin (each reported side effect of Humalog and Lyumjev) | All adverse events related to insulin for all twelve participants were recorded | Posted | Number | Reported insulin side effect | 68 days (whole study period) |
|
|
|
| Secondary | Pharmacodynamic Parameters: Euglycemia | Percentage of time the glucose level is between 3.9 and 10 mmol/l (%) | AP settings for standard treatment (Humalog) were already optimal as a result of long term regular care. However, in the Lyumjev-Humalog sequence, these optimal AP settings were not set again when starting with Humalog. Instead, optimized settings for Lyumjev were used. This procedural error with an unknown influence on glucose regulation rendered a reliable cross-over comparison impossible, which required exclusion of the AP data from these five participants before data analysis. | Posted | Mean | Standard Deviation | percentage of time spent in range | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
|
|
|
| Secondary | Pharmacodynamic Parameters: Hypoglycemia | Percentage of time the glucose level is below 3.9 mmol/l (%) | AP settings for standard treatment (Humalog) were already optimal as a result of long term regular care. However, in the Lyumjev-Humalog sequence, these optimal AP settings were not set again when starting with Humalog. Instead, optimized settings for Lyumjev were used. This procedural error with an unknown influence on glucose regulation rendered a reliable cross-over comparison impossible, which required exclusion of the AP data from these five participants before data analysis. | Posted | Mean | Standard Deviation | percentage of time spent below range | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
|
|
|
| Secondary | Pharmacodynamic Parameters: Mean Glucose Value | Mean of the glucose values (parameter required to determine the coefficient of variation) | AP settings for standard treatment (Humalog) were already optimal as a result of long term regular care. However, in the Lyumjev-Humalog sequence, these optimal AP settings were not set again when starting with Humalog. Instead, optimized settings for Lyumjev were used. This procedural error with an unknown influence on glucose regulation rendered a reliable cross-over comparison impossible, which required exclusion of the AP data from these five participants before data analysis. | Posted | Mean | Standard Deviation | mmol/L | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
|
|
|
| Secondary | Pharmacodynamic Parameters: Standard Deviation of Glucose Value | Standard deviation of the glucose values (parameter required to determine the coefficient of variation) | AP settings for standard treatment (Humalog) were already optimal as a result of long term regular care. However, in the Lyumjev-Humalog sequence, these optimal AP settings were not set again when starting with Humalog. Instead, optimized settings for Lyumjev were used. This procedural error with an unknown influence on glucose regulation rendered a reliable cross-over comparison impossible, which required exclusion of the AP data from these five participants before data analysis. | Posted | Median | Inter-Quartile Range | mmol/L | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
|
|
|
| Secondary | Pharmacodynamic Parameters: Glycemic Variability (CoV) | Glycemic variability expressed as the coefficient of variation (CoV): standard deviation divided by the mean of the glucose values (%) | AP settings for standard treatment (Humalog) were already optimal as a result of long term regular care. However, in the Lyumjev-Humalog sequence, these optimal AP settings were not set again when starting with Humalog. Instead, optimized settings for Lyumjev were used. This procedural error with an unknown influence on glucose regulation rendered a reliable cross-over comparison impossible, which required exclusion of the AP data from these five participants before data analysis. | Posted | Mean | Standard Deviation | percentage | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
|
|
|
| Secondary | Pharmacodynamic Parameters: Glycemic Variability (IQR) | Glycemic variability expressed as the interquartile range (IQR) (mmol/l) | AP settings for standard treatment (Humalog) were already optimal as a result of long term regular care. However, in the Lyumjev-Humalog sequence, these optimal AP settings were not set again when starting with Humalog. Instead, optimized settings for Lyumjev were used. This procedural error with an unknown influence on glucose regulation rendered a reliable cross-over comparison impossible, which required exclusion of the AP data from these five participants before data analysis. | Posted | Mean | Standard Deviation | mmol/L | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
|
|
|
| Secondary | AP-related Parameters: Daily Insulin Usage (Units) | Daily insulin usage (units) | AP settings for standard treatment (Humalog) were already optimal as a result of long term regular care. However, in the Lyumjev-Humalog sequence, these optimal AP settings were not set again when starting with Humalog. Instead, optimized settings for Lyumjev were used. This procedural error with an unknown influence on glucose regulation rendered a reliable cross-over comparison impossible, which required exclusion of the AP data from these five participants before data analysis. | Posted | Mean | Standard Deviation | units per day | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
|
|
|
| Secondary | AP-related Parameters: Glucagon Usage | Daily usage of glucagon (mg) | AP settings for standard treatment (Humalog) were already optimal as a result of long term regular care. However, in the Lyumjev-Humalog sequence, these optimal AP settings were not set again when starting with Humalog. Instead, optimized settings for Lyumjev were used. This procedural error with an unknown influence on glucose regulation rendered a reliable cross-over comparison impossible, which required exclusion of the AP data from these five participants before data analysis. | Posted | Mean | Standard Deviation | mg per day | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
|
|
|
| Secondary | AP-related Parameters: Algorithm Activity | Percentage of time the algorithm is active (%) | AP settings for standard treatment (Humalog) were already optimal as a result of long term regular care. However, in the Lyumjev-Humalog sequence, these optimal AP settings were not set again when starting with Humalog. Instead, optimized settings for Lyumjev were used. This procedural error with an unknown influence on glucose regulation rendered a reliable cross-over comparison impossible, which required exclusion of the AP data from these five participants before data analysis. | Posted | Mean | Standard Deviation | Percentage of time | 25 days for each intervention period (50 days in total; 5-day training period and washout period excluded from analysis; data were continuously acquired) |
|
|
|
| 12 |
| 0 |
| 12 |
| 4 |
| 12 |
| EG001 | Humalog (Insulin Lispro) | Use of Humalog (during both sequences) | 0 | 12 | 0 | 12 | 1 | 12 |
| Subcutaneous bump (insulin) | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Pain at infusion site (insulin) | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| (sensation of) hyperglycemia | Endocrine disorders | Systematic Assessment |
|
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| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |