Diabetes Mellitus, Type 1
Conditions
Keywords
glucagon, Type 1 diabetes mellitus, Bionic Pancreas, diabetes, iLet, iPhone, Beta Bionics, Anti-hypoglycemia, Glucagon Analog
Brief summary
The purpose of this study was to determine whether the Bionic Pancreas with ZP4207 (dasiglucagon\*) was feasible to improve glycemic control in adults with type 1 diabetes mellitus. \*dasiglucagon is the proposed International Nonproprietary Name (pINN) for ZP4207
Detailed description
This was a single-center, open-label, 2-part, randomized cross-over trial. The trial was to enrol up to 20 adult patients with type 1 diabetes mellitus and assess the safety and efficacy of the Bionic Pancreas (BP) using either the iLet or iPhone platform when used with the glucagon analogue ZP4207 (dasiglucagon) versus Lilly glucagon. In Part 1, patients participated in two 1-day treatment arms in random order (iPhone-based BP using ZP4207 (dasiglucagon) and iPhone-based BP using Lilly glucagon) according to a pre-generated randomization scheme. In Part 2, it was planned to enrol additional patients to participate in two 1-day treatment arms in random order (iLet using ZP4207 (dasiglucagon) and iLet using Lilly glucagon) according to a pre-generated randomization scheme. However, due to unavailability of the iLet, the sponsor decided to stop the trial upon completion of Part 1. Part 2 of the trial using the iLet was consequently not conducted. One day the BP will use glucagon analogue ZP4207 (dasiglucagon) and the other day the BP will use Lilly glucagon. Subjects will also receive insulin lispro through the BP on both days. The trial will be conducted at single center, the Massachusetts General Hospital Diabetes Center in Boston, MA.
Interventions
DRUGInsulin Lispro
Used to lower blood glucose. Commercially available by prescription and is indicated for patients with type 1 diabetes mellitus (T1DM), but not for use in a bionic pancreas. Individualized dose based on metabolic needs and frequent monitoring of blood glucose.
DRUGZP4207 (dasiglucagon)
A glucagon analog not yet approved by the FDA. Subcutaneous administration in one BP arm.
DRUGGlucagon
A hormone normally made by the pancreas to raise blood glucose. Used to treat low blood sugar. Commercially available by prescription and is indicated for patients with T1DM in severe hypoglycemia, but not for use in a BP. Subcutaneous administration in one BP arm.
DEVICEiPhone-based bionic pancreas
An experimental device.
DEVICEiLet-based bionic pancreas
An experimental device.
Sponsors
Massachusetts General Hospital
Beta Bionics, Inc.
Zealand Pharma
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with T1DM for at least 1 year, as defined by the American Diabetes Association 2. Age ≥ 18 years 3. Prescription medication regimen stable for \>1 month (except for medications not expected to affect trial safety or outcome, in the judgment of the investigator) 4. Diabetes managed using an insulin pump for \>=6 months 5. Patients in good health according to age (medical history, physical examination, vital signs, 12-lead electrocardiograms \[ECGs\], laboratory assessments), as judged by the Investigator
Exclusion criteria
1. Previous exposure to ZP4207 or adverse reaction to glucagon 2. History of liver disease or current abnormal liver function tests (LFTs) 3. Renal failure 4. Anemia 5. History of coronary artery disease or congestive heart failure (class III or IV) 6. History of transient ischemic attack or stroke 7. Seizure disorder 8. Cystic fibrosis, pancreatitis, or any other pancreatic disease besides T1DM 9. Other endocrine disorders 10. Use of oral anti-diabetic medications 11. Electronically powered implants 12. Hypertension (≥160/100 mm Hg despite treatment) 13. Inadequate venous (vein) access as determined by trial nurse or physician at time of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Up to 50 days | Safety and tolerability of ZP4207 in the BP using either the iPhone or the iLet platform, as measured by adverse events (AEs), local tolerability of infusion site reactions, and clinical laboratory parameters. See adverse events section for results on AEs by system organ class and preferred term. Clinical laboratory parameters in terms of overall 'investigations' AEs and abnormal hematology parameters that did not resolve by the follow-up visit are presented below. LLN = lower limit of the normal range. Investigations and vital signs AEs by preferred term are presented in the AE section. Participants with infusion site pain and nausea measured by visual analog scales (VAS) are presented below; mean values are presented under secondary outcomes. For the VAS, individuals marked on a 10-cm line corresponding to the amount of pain or nausea being experienced, with low scores (cm) indicating no feelings of pain or nausea and high scores (cm) indicating high feelings of pain or nausea. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nausea Measured on a Visual Analog Scale (VAS) | 16 hours | The VAS scale was used to measure nausea at the end of the visit (16 hours) for patients in both treatment groups. The VAS was a psychometric response scale used to measure subjective characteristics of nausea. Patients marked a location on a 0 to 10-cm line that corresponded to the amount of nausea being experienced, with low scores (cm) indicating no feelings of nausea and high scores (cm) indicating high feelings of nausea. Actual values are shown. The maximum values in both groups were recorded at hour 6, the start of the exercise period. |
| Glycemic Regulation | 16 hours | Measure glycemic regulation, including hypoglycemia exposure (percent of time spent with continuous glucose monitor \[CGM\] glucose\<60mg/dL) |
| Average Percent Glucagon Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump. | 16 hours | Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis. |
| Average Percent Insulin Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump. | 16 hours | Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis. |
| Average Percentage of Time During Which the Bionic Pancreas is Functioning Nominally in All Respects Based on Real-time Continuous Glucose Monitoring (CGM) Data | 16 hours | Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis. |
| Average Percentage of Time During Which the Bionic Pancreas is Functioning Nominally With or Without a New CGM Glucose Reading Captured | 16 hours | Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis. |
| CGM Reliability Index, Calculated as Percentage of Possible Values Actually Recorded by CGM | 16 hours | Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis. |
| CGM Mean Absolute Relative Difference Versus Time-stamped Blood Glucose (BG) Values From Meter Download | 16 hours | Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis. |
| Pain Measured on a Visual Analog Scale (VAS) | 16 hours | The VAS scale was used to measure pain at the end of the visit (16 hours) for patients in both treatment groups. The VAS was a psychometric response scale used to measure subjective characteristics of pain. Patients marked a location on a 0 to 10-cm line that corresponded to the amount of pain being experienced, with low scores (cm) indicating no feelings of pain and high scores (cm) indicating high feelings of pain. Actual values are shown. The maximum value in the Lilly glucagon group was recorded at hour 3. |
| Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Connectivity Issues | 16 hours | Technical faults related to connectivity issues were listed |
| Diabetes Treatment Satisfaction Questionnaire - Status | Up to 3 months | This questionnaire was not assessed as per protocol amendment 7. |
| Diabetes Treatment Satisfaction Questionnaire - Change | Up to 3 months | This questionnaire was not assessed as per protocol amendment 7. |
| T1-Diabetes Distress Scale | Up to 3 months | This questionnaire was not assessed as per protocol amendment 7. |
| Problem Areas in Diabetes Survey | Up to 3 months | This questionnaire was not assessed as per protocol amendment 7. |
| Hypoglycemia Fear Survey | Up to 3 months | This questionnaire was not assessed as per protocol amendment 7. |
| Impact of Daily Diabetes Demands | Up to 3 months | This questionnaire was not assessed as per protocol amendment 7. |
| Bionic Pancreas User Opinion Survey | Up to 3 months | This questionnaire was not assessed as per protocol amendment 7. |
| Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Calibration Issues | 16 hours | Technical faults in terms of calibration issues were listed by patient. |
Countries
United States
Participant flow
Recruitment details
In Part 1, it was planned to enrol 10 patients in two 1-day treatment arms in random order (iPhone-based bionic pancreas using ZP4207 or Lilly Glucagon) according to a pre-generated randomization scheme. The trial had a crossover design. In all, 19 patients were screened and 13 were randomized, but 1 patient withdrew before treatment. Thus, 12 patients were randomized and treated.
Pre-assignment details
Part 2 was designed to enroll up to 10 new patients in two 1-day treatment arms in random order (iLet using ZP4207 or Lilly Glucagon). However, due to unavailability of the iLet, the sponsor decided to stop the trial upon completion of Part 1. Part 2 of the trial using the iLet was consequently not conducted.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, All Participants In Part 1, 12 patients participated in 1-day treatment arms in random order (iPhone-based Bionic Pancreas using Lilly glucagon and iPhone-based Bionic Pancreas using ZP4207 (dasiglucagon) {experimental drug} with insulin lispro) according to pre-generated randomization scheme. Note: 13 patients were enrolled and 1 patient withdrew prior to treatment with either trial drug; thus, 12 patients were randomized and treated.
Insulin Lispro: Used to lower blood glucose. Commercially available by prescription and is indicated for patients with T1DM, but not for use in a bionic pancreas. Individualized dose based on metabolic needs and frequent monitoring of blood glucose.
ZP4207 (dasiglucagon): A glucagon analog not yet approved by the FDA. Subcutaneous administration in one BP arm.
Glucagon: A hormone normally made by the pancreas to raise blood glucose. Used to treat low blood sugar. Commercially available by prescription and is indicated for patients with T1DM in severe hypoglycemia, but not for use in a BP. Subcutaneous administration in one BP arm.
iPhone-based bionic pancreas: An experimental device. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Logistical challenges | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1, All Participants |
|---|---|
| Age, Continuous | 42.5 Years STANDARD_DEVIATION 18.47 |
| BMI | 27.36 kg/m^2 STANDARD_DEVIATION 5.301 |
| Body weight | 80.28 kg STANDARD_DEVIATION 18.357 |
| Diabetes duration | 28.2 years STANDARD_DEVIATION 14.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| HbA1c | 7.18 % STANDARD_DEVIATION 1.462 |
| 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 | 1 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 12 |
| other Total, other adverse events | 8 / 10 | 12 / 12 |
| serious Total, serious adverse events | 0 / 10 | 0 / 12 |
Outcome results
Primary
Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters
Safety and tolerability of ZP4207 in the BP using either the iPhone or the iLet platform, as measured by adverse events (AEs), local tolerability of infusion site reactions, and clinical laboratory parameters. See adverse events section for results on AEs by system organ class and preferred term. Clinical laboratory parameters in terms of overall 'investigations' AEs and abnormal hematology parameters that did not resolve by the follow-up visit are presented below. LLN = lower limit of the normal range. Investigations and vital signs AEs by preferred term are presented in the AE section. Participants with infusion site pain and nausea measured by visual analog scales (VAS) are presented below; mean values are presented under secondary outcomes. For the VAS, individuals marked on a 10-cm line corresponding to the amount of pain or nausea being experienced, with low scores (cm) indicating no feelings of pain or nausea and high scores (cm) indicating high feelings of pain or nausea.
Time frame: Up to 50 days
Population: The full analysis set (intent-to-treat population) consisted of all randomized patients: 10 patients received ZP4207 treatment and 12 patients received Lilly Glucagon treatment in a crossover design. Results are presented by treatment received. Only Part 1 of the trial was conducted.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, ZP4207 | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with AEs | 8 Participants |
| Part 1, ZP4207 | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with antibodies | 0 Participants |
| Part 1, ZP4207 | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with edema infusion site reactions | 0 Participants |
| Part 1, ZP4207 | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with erythema infusion site reactions | 0 Participants |
| Part 1, ZP4207 | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with investigations AEs | 2 Participants |
| Part 1, ZP4207 | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with erythrocytes <LLN | 0 Participants |
| Part 1, ZP4207 | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with hematocrit <LLN | 0 Participants |
| Part 1, ZP4207 | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with hemoglobin <LLN | 0 Participants |
| Part 1, ZP4207 | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with lymphocytes <LLN | 0 Participants |
| Part 1, ZP4207 | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with infusion site pain (VAS) | 0 Participants |
| Part 1, ZP4207 | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with nausea (VAS) | 4 Participants |
| Part 1, ZP4207 | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with vascular disorders | 1 Participants |
| Part 1, Lilly Glucagon | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with nausea (VAS) | 2 Participants |
| Part 1, Lilly Glucagon | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with AEs | 12 Participants |
| Part 1, Lilly Glucagon | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with hematocrit <LLN | 1 Participants |
| Part 1, Lilly Glucagon | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with antibodies | 0 Participants |
| Part 1, Lilly Glucagon | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with infusion site pain (VAS) | 2 Participants |
| Part 1, Lilly Glucagon | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with edema infusion site reactions | 0 Participants |
| Part 1, Lilly Glucagon | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with hemoglobin <LLN | 2 Participants |
| Part 1, Lilly Glucagon | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with erythema infusion site reactions | 0 Participants |
| Part 1, Lilly Glucagon | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with vascular disorders | 1 Participants |
| Part 1, Lilly Glucagon | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with investigations AEs | 2 Participants |
| Part 1, Lilly Glucagon | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with lymphocytes <LLN | 1 Participants |
| Part 1, Lilly Glucagon | Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters | Participants with erythrocytes <LLN | 1 Participants |
Secondary
Average Percentage of Time During Which the Bionic Pancreas is Functioning Nominally in All Respects Based on Real-time Continuous Glucose Monitoring (CGM) Data
Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis.
Time frame: 16 hours
Population: The full analysis set (intent-to-treat population) consisted of all randomized patients: 10 patients received ZP4207 treatment and 12 patients received Lilly Glucagon treatment in a crossover design. Results are presented by treatment received. Only Part 1 of the trial was conducted.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1, ZP4207 | Average Percentage of Time During Which the Bionic Pancreas is Functioning Nominally in All Respects Based on Real-time Continuous Glucose Monitoring (CGM) Data | 95.41 percentage of time functioning nominally | Standard Deviation 1.846 |
| Part 1, Lilly Glucagon | Average Percentage of Time During Which the Bionic Pancreas is Functioning Nominally in All Respects Based on Real-time Continuous Glucose Monitoring (CGM) Data | 94.26 percentage of time functioning nominally | Standard Deviation 3.966 |
Secondary
Average Percentage of Time During Which the Bionic Pancreas is Functioning Nominally With or Without a New CGM Glucose Reading Captured
Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis.
Time frame: 16 hours
Population: The full analysis set (intent-to-treat population) consisted of all randomized patients: 10 patients received ZP4207 treatment and 12 patients received Lilly Glucagon treatment in a crossover design. Results are presented by treatment received. Only Part 1 of the trial was conducted.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1, ZP4207 | Average Percentage of Time During Which the Bionic Pancreas is Functioning Nominally With or Without a New CGM Glucose Reading Captured | 97.86 percentage of time functioning nominally | Standard Deviation 1.125 |
| Part 1, Lilly Glucagon | Average Percentage of Time During Which the Bionic Pancreas is Functioning Nominally With or Without a New CGM Glucose Reading Captured | 96.31 percentage of time functioning nominally | Standard Deviation 3.891 |
Secondary
Average Percent Glucagon Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump.
Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis.
Time frame: 16 hours
Population: The full analysis set (intent-to-treat population) consisted of all randomized patients: 10 patients received ZP4207 treatment and 12 patients received Lilly Glucagon treatment in a crossover design. Results are presented by treatment received. Only Part 1 of the trial was conducted.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1, ZP4207 | Average Percent Glucagon Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump. | 96.73 Percentage of treatment delivered | Standard Deviation 4.021 |
| Part 1, Lilly Glucagon | Average Percent Glucagon Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump. | 97.01 Percentage of treatment delivered | Standard Deviation 2.851 |
Comparison: A paired t-test or the Wilcoxon signed rank test for comparison of means with normally or non normally distributed residuals, respectively, was used. The Shapiro-Wilk test was used to determine the normality of the residuals for each comparison. The residuals were obtained from an analysis of variance (ANOVA) model with treatment group as the fixed effect. If the p-value of the test was \<0.001, the non-parametric method was utilized to analyze the endpoint parameter.p-value: 0.850895% CI: [-3.55, 2.99]t-test, 2 sided
Comparison: Non-parametric method p-value was from a Wilcoxon signed rank text. The normality of the residuals was assessed using the Shapiro-Wilk test, where the residuals were obtained from an ANOVA model with treatment group as the fixed effect. A patient was required to have data for both periods to be included in the pre-specified analysis for a given endpoint.p-value: >0.999995% CI: [-4.12, 3.13]Wilcoxon (Mann-Whitney)
Secondary
Average Percent Insulin Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump.
Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis.
Time frame: 16 hours
Population: The full analysis set (intent-to-treat population) consisted of all randomized patients: 10 patients received ZP4207 treatment and 12 patients received Lilly Glucagon treatment in a crossover design. Results are presented by treatment received. Only Part 1 of the trial was conducted.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1, ZP4207 | Average Percent Insulin Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump. | 98.36 Percentage of treatment delivered | Standard Deviation 1.114 |
| Part 1, Lilly Glucagon | Average Percent Insulin Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump. | 97.73 Percentage of treatment delivered | Standard Deviation 2.051 |
Comparison: A paired t-test or the Wilcoxon signed rank test for comparison of means with normally or non normally distributed residuals, respectively, was used. The Shapiro-Wilk test was used to determine the normality of the residuals for each comparison. The residuals were obtained from an analysis of variance (ANOVA) model with treatment group as the fixed effect. If the p-value of the test was \<0.001, the non-parametric method was utilized to analyze the endpoint parameter.p-value: 0.184795% CI: [-0.36, 1.62]t-test, 2 sided
Comparison: Non-parametric method p-value was from a Wilcoxon signed rank text. The normality of the residuals was assessed using the Shapiro-Wilk test, where the residuals were obtained from an ANOVA model with treatment group as the fixed effect. A patient was required to have data for both periods to be included in the pre-specified analysis for a given endpoint.p-value: 0.078195% CI: [-0.01, 3.09]Wilcoxon (Mann-Whitney)
Secondary
Bionic Pancreas User Opinion Survey
This questionnaire was not assessed as per protocol amendment 7.
Time frame: Up to 3 months
Population: This questionnaire was not assessed as per protocol amendment 7.
Secondary
CGM Mean Absolute Relative Difference Versus Time-stamped Blood Glucose (BG) Values From Meter Download
Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis.
Time frame: 16 hours
Population: The full analysis set (intent-to-treat population) consisted of all randomized patients: 10 patients received ZP4207 treatment and 12 patients received Lilly Glucagon treatment in a crossover design. Results are presented by treatment received. Only Part 1 of the trial was conducted.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1, ZP4207 | CGM Mean Absolute Relative Difference Versus Time-stamped Blood Glucose (BG) Values From Meter Download | 12.6 mg/dL | Standard Deviation 4.13 |
| Part 1, Lilly Glucagon | CGM Mean Absolute Relative Difference Versus Time-stamped Blood Glucose (BG) Values From Meter Download | 12.7 mg/dL | Standard Deviation 5.43 |
Secondary
CGM Reliability Index, Calculated as Percentage of Possible Values Actually Recorded by CGM
Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis.
Time frame: 16 hours
Population: The full analysis set (intent-to-treat population) consisted of all randomized patients: 10 patients received ZP4207 treatment and 12 patients received Lilly Glucagon treatment in a crossover design. Results are presented by treatment received. Only Part 1 of the trial was conducted.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1, ZP4207 | CGM Reliability Index, Calculated as Percentage of Possible Values Actually Recorded by CGM | 97.55 percentage of recorded values | Standard Deviation 1.219 |
| Part 1, Lilly Glucagon | CGM Reliability Index, Calculated as Percentage of Possible Values Actually Recorded by CGM | 97.94 percentage of recorded values | Standard Deviation 1.076 |
Secondary
Diabetes Treatment Satisfaction Questionnaire - Change
This questionnaire was not assessed as per protocol amendment 7.
Time frame: Up to 3 months
Population: This questionnaire was not assessed as per protocol amendment 7.
Secondary
Diabetes Treatment Satisfaction Questionnaire - Status
This questionnaire was not assessed as per protocol amendment 7.
Time frame: Up to 3 months
Population: This questionnaire was not assessed as per protocol amendment 7.
Secondary
Glycemic Regulation
Measure glycemic regulation, including hypoglycemia exposure (percent of time spent with continuous glucose monitor \[CGM\] glucose\<60mg/dL)
Time frame: 16 hours
Population: The full analysis set (intent-to-treat population) consisted of all randomized patients: 10 patients received ZP4207 treatment and 12 patients received Lilly Glucagon treatment in a crossover design. Results are presented by treatment received. Only Part 1 of the trial was conducted.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1, ZP4207 | Glycemic Regulation | 12.78 percentage of time points | Standard Deviation 17.262 |
| Part 1, Lilly Glucagon | Glycemic Regulation | 17.60 percentage of time points | Standard Deviation 14.08 |
Comparison: A paired t-test or the Wilcoxon signed rank test for comparison of means with normally or non normally distributed residuals, respectively, was used. The Shapiro-Wilk test was used to determine the normality of the residuals for each comparison. The residuals were obtained from an analysis of variance (ANOVA) model with treatment group as the fixed effect. If the p-value of the test was \<0.001, the non-parametric method was utilized to analyze the endpoint parameter.p-value: 0.251895% CI: [-19.63, 5.84]t-test, 2 sided
Comparison: Non-parametric method p-value was from a Wilcoxon signed rank text. The normality of the residuals was assessed using the Shapiro-Wilk test, where the residuals were obtained from an ANOVA model with treatment group as the fixed effect. A patient was required to have data for both periods to be included in the pre-specified analysis for a given endpoint.p-value: 0.2595% CI: [-25.85, 10.68]Wilcoxon (Mann-Whitney)
Secondary
Hypoglycemia Fear Survey
This questionnaire was not assessed as per protocol amendment 7.
Time frame: Up to 3 months
Population: This questionnaire was not assessed as per protocol amendment 7.
Secondary
Impact of Daily Diabetes Demands
This questionnaire was not assessed as per protocol amendment 7.
Time frame: Up to 3 months
Population: This questionnaire was not assessed as per protocol amendment 7.
Secondary
Nausea Measured on a Visual Analog Scale (VAS)
The VAS scale was used to measure nausea at the end of the visit (16 hours) for patients in both treatment groups. The VAS was a psychometric response scale used to measure subjective characteristics of nausea. Patients marked a location on a 0 to 10-cm line that corresponded to the amount of nausea being experienced, with low scores (cm) indicating no feelings of nausea and high scores (cm) indicating high feelings of nausea. Actual values are shown. The maximum values in both groups were recorded at hour 6, the start of the exercise period.
Time frame: 16 hours
Population: The full analysis set (intent-to-treat population) consisted of all randomized patients: 10 patients received ZP4207 treatment and 12 patients received Lilly Glucagon treatment in a crossover design. Results are presented by treatment received. Only Part 1 of the trial was conducted.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, ZP4207 | Nausea Measured on a Visual Analog Scale (VAS) | Hour 1 | 0.12 cm | Standard Deviation 0.379 |
| Part 1, ZP4207 | Nausea Measured on a Visual Analog Scale (VAS) | Hour 5 | 0.02 cm | Standard Deviation 0.063 |
| Part 1, ZP4207 | Nausea Measured on a Visual Analog Scale (VAS) | Hour 3 | 0.11 cm | Standard Deviation 0.348 |
| Part 1, ZP4207 | Nausea Measured on a Visual Analog Scale (VAS) | Hour 6 | 0.29 cm | Standard Deviation 0.917 |
| Part 1, ZP4207 | Nausea Measured on a Visual Analog Scale (VAS) | Hour 2 | 0.00 cm | Standard Deviation 0 |
| Part 1, ZP4207 | Nausea Measured on a Visual Analog Scale (VAS) | Hour 7 | 0.00 cm | Standard Deviation 0 |
| Part 1, ZP4207 | Nausea Measured on a Visual Analog Scale (VAS) | Hour 4 | 0.00 cm | Standard Deviation 0 |
| Part 1, ZP4207 | Nausea Measured on a Visual Analog Scale (VAS) | Visit end (16 hours) | 0.11 cm | Standard Deviation 0.348 |
| Part 1, ZP4207 | Nausea Measured on a Visual Analog Scale (VAS) | Baseline | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Nausea Measured on a Visual Analog Scale (VAS) | Visit end (16 hours) | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Nausea Measured on a Visual Analog Scale (VAS) | Baseline | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Nausea Measured on a Visual Analog Scale (VAS) | Hour 1 | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Nausea Measured on a Visual Analog Scale (VAS) | Hour 2 | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Nausea Measured on a Visual Analog Scale (VAS) | Hour 3 | 0.04 cm | Standard Deviation 0.144 |
| Part 1, Lilly Glucagon | Nausea Measured on a Visual Analog Scale (VAS) | Hour 4 | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Nausea Measured on a Visual Analog Scale (VAS) | Hour 5 | 0.09 cm | Standard Deviation 0.215 |
| Part 1, Lilly Glucagon | Nausea Measured on a Visual Analog Scale (VAS) | Hour 6 | 0.18 cm | Standard Deviation 0.522 |
| Part 1, Lilly Glucagon | Nausea Measured on a Visual Analog Scale (VAS) | Hour 7 | 0.00 cm | Standard Deviation 0 |
Secondary
Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Calibration Issues
Technical faults in terms of calibration issues were listed by patient.
Time frame: 16 hours
Population: The full analysis set (intent-to-treat population) consisted of all randomized patients: 10 patients received ZP4207 treatment and 12 patients received Lilly Glucagon treatment in a crossover design. Results are presented by treatment received. Only Part 1 of the trial was conducted.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, ZP4207 | Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Calibration Issues | 9 Participants |
| Part 1, Lilly Glucagon | Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Calibration Issues | 11 Participants |
Secondary
Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Connectivity Issues
Technical faults related to connectivity issues were listed
Time frame: 16 hours
Population: The full analysis set (intent-to-treat population) consisted of all randomized patients: 10 patients received ZP4207 treatment and 12 patients received Lilly Glucagon treatment in a crossover design. Results are presented by treatment received. Only Part 1 of the trial was conducted.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, ZP4207 | Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Connectivity Issues | 3 Participants |
| Part 1, Lilly Glucagon | Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Connectivity Issues | 2 Participants |
Secondary
Pain Measured on a Visual Analog Scale (VAS)
The VAS scale was used to measure pain at the end of the visit (16 hours) for patients in both treatment groups. The VAS was a psychometric response scale used to measure subjective characteristics of pain. Patients marked a location on a 0 to 10-cm line that corresponded to the amount of pain being experienced, with low scores (cm) indicating no feelings of pain and high scores (cm) indicating high feelings of pain. Actual values are shown. The maximum value in the Lilly glucagon group was recorded at hour 3.
Time frame: 16 hours
Population: The full analysis set (intent-to-treat population) consisted of all randomized patients: 10 patients received ZP4207 treatment and 12 patients received Lilly Glucagon treatment in a crossover design. Results are presented by treatment received. Only Part 1 of the trial was conducted.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, ZP4207 | Pain Measured on a Visual Analog Scale (VAS) | Hour 1 | 0.00 cm | Standard Deviation 0 |
| Part 1, ZP4207 | Pain Measured on a Visual Analog Scale (VAS) | Hour 5 | 0.00 cm | Standard Deviation 0 |
| Part 1, ZP4207 | Pain Measured on a Visual Analog Scale (VAS) | Hour 3 | 0.00 cm | Standard Deviation 0 |
| Part 1, ZP4207 | Pain Measured on a Visual Analog Scale (VAS) | Hour 6 | 0.00 cm | Standard Deviation 0 |
| Part 1, ZP4207 | Pain Measured on a Visual Analog Scale (VAS) | Hour 2 | 0.00 cm | Standard Deviation 0 |
| Part 1, ZP4207 | Pain Measured on a Visual Analog Scale (VAS) | Hour 7 | 0.00 cm | Standard Deviation 0 |
| Part 1, ZP4207 | Pain Measured on a Visual Analog Scale (VAS) | Hour 4 | 0.00 cm | Standard Deviation 0 |
| Part 1, ZP4207 | Pain Measured on a Visual Analog Scale (VAS) | Visit end (16 hours) | 0.00 cm | Standard Deviation 0 |
| Part 1, ZP4207 | Pain Measured on a Visual Analog Scale (VAS) | Baseline | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Pain Measured on a Visual Analog Scale (VAS) | Visit end (16 hours) | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Pain Measured on a Visual Analog Scale (VAS) | Baseline | 0.01 cm | Standard Deviation 0.0029 |
| Part 1, Lilly Glucagon | Pain Measured on a Visual Analog Scale (VAS) | Hour 1 | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Pain Measured on a Visual Analog Scale (VAS) | Hour 2 | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Pain Measured on a Visual Analog Scale (VAS) | Hour 3 | 0.06 cm | Standard Deviation 0.202 |
| Part 1, Lilly Glucagon | Pain Measured on a Visual Analog Scale (VAS) | Hour 4 | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Pain Measured on a Visual Analog Scale (VAS) | Hour 5 | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Pain Measured on a Visual Analog Scale (VAS) | Hour 6 | 0.00 cm | Standard Deviation 0 |
| Part 1, Lilly Glucagon | Pain Measured on a Visual Analog Scale (VAS) | Hour 7 | 0.02 cm | Standard Deviation 0.058 |
Secondary
Problem Areas in Diabetes Survey
This questionnaire was not assessed as per protocol amendment 7.
Time frame: Up to 3 months
Population: This questionnaire was not assessed as per protocol amendment 7.
Secondary
T1-Diabetes Distress Scale
This questionnaire was not assessed as per protocol amendment 7.
Time frame: Up to 3 months
Population: This questionnaire was not assessed as per protocol amendment 7.