Feasibility Trial Testing the Bionic Pancreas With ZP4207

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Bionic Pancreas Feasibility Trial Testing the Bionic Pancreas With ZP4207

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Insulin Lispro
* Drug: ZP4207 (dasiglucagon)
* Drug: Glucagon
* Device: iPhone-based bionic pancreas
* Device: iLet-based bionic pancreas


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with T1DM for at least 1 year, as defined by the American Diabetes Association Age ≥ 18 years Prescription medication regimen stable for >1 month (except for medications not expected to affect trial safety or outcome, in the judgment of the investigator) Diabetes managed using an insulin pump for >=6 months 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: Previous exposure to ZP4207 or adverse reaction to glucagon History of liver disease or current abnormal liver function tests (LFTs) Renal failure Anemia History of coronary artery disease or congestive heart failure (class III or IV) History of transient ischemic attack or stroke Seizure disorder Cystic fibrosis, pancreatitis, or any other pancreatic disease besides T1DM Other endocrine disorders Use of oral anti-diabetic medications Electronically powered implants Hypertension (≥160/100 mm Hg despite treatment) Inadequate venous (vein) access as determined by trial nurse or physician at time of screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1, Lilly glucagon then ZP4207<br>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. | Drug: Insulin Lispro<br>* 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.<br>* Other names: HumaLOG KwikPen;Drug: ZP4207 (dasiglucagon)<br>* A glucagon analog not yet approved by the FDA. Subcutaneous administration in one BP arm.<br>* Other names: dasiglucagon;Drug: Glucagon<br>* 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.<br>* Other names: Glucagon for injection (rDNA original);Device: iPhone-based bionic pancreas<br>* An experimental device.<br>|
| Experimental: Part 1, ZP4207 then Lilly Glucagon<br>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. | Drug: Insulin Lispro<br>* 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.<br>* Other names: HumaLOG KwikPen;Drug: ZP4207 (dasiglucagon)<br>* A glucagon analog not yet approved by the FDA. Subcutaneous administration in one BP arm.<br>* Other names: dasiglucagon;Drug: Glucagon<br>* 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.<br>* Other names: Glucagon for injection (rDNA original);Device: iPhone-based bionic pancreas<br>* An experimental device.<br>|
| Experimental: Part 2, Lilly glucagon then ZP4207<br>In Part 2, it was planned to enrol up to 10 new patients to participate in 1-day treatment arms in random order (iLet-based Bionic Pancreas using Lilly glucagon and iLet-based Bionic Pancreas using ZP4207 (dasiglucagon) {experimental drug} with insulin lispro) according to 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. | Drug: Insulin Lispro<br>* 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.<br>* Other names: HumaLOG KwikPen;Drug: ZP4207 (dasiglucagon)<br>* A glucagon analog not yet approved by the FDA. Subcutaneous administration in one BP arm.<br>* Other names: dasiglucagon;Drug: Glucagon<br>* 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.<br>* Other names: Glucagon for injection (rDNA original);Device: iLet-based bionic pancreas<br>* An experimental device.<br>|
| Experimental: Part 2, ZP4207 then Lilly Glucagon<br>In Part 2, it was planned to enrol up to 10 new patients to participate in 1-day treatment arms in random order (iLet-based Bionic Pancreas using Lilly glucagon and iLet-based Bionic Pancreas using ZP4207 (dasiglucagon) {experimental drug} with insulin lispro) according to 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. | Drug: Insulin Lispro<br>* 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.<br>* Other names: HumaLOG KwikPen;Drug: ZP4207 (dasiglucagon)<br>* A glucagon analog not yet approved by the FDA. Subcutaneous administration in one BP arm.<br>* Other names: dasiglucagon;Drug: Glucagon<br>* 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.<br>* Other names: Glucagon for injection (rDNA original);Device: iLet-based bionic pancreas<br>* An experimental device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 50 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 16 hours | 
| 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. | 16 hours | 
| Glycemic Regulation | Measure glycemic regulation, including hypoglycemia exposure (percent of time spent with continuous glucose monitor [CGM] glucose<60mg/dL) | 16 hours | 
| 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. | 16 hours | 
| 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. | 16 hours | 
| 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. | 16 hours | 
| 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. | 16 hours | 
| 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. | 16 hours | 
| 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. | 16 hours | 
| 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. | 16 hours | 
| Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Connectivity Issues | Technical faults related to connectivity issues were listed | 16 hours | 
| Diabetes Treatment Satisfaction Questionnaire - Status | This questionnaire was not assessed as per protocol amendment 7. | Up to 3 months | 
| Diabetes Treatment Satisfaction Questionnaire - Change | This questionnaire was not assessed as per protocol amendment 7. | Up to 3 months | 
| T1-Diabetes Distress Scale | This questionnaire was not assessed as per protocol amendment 7. | Up to 3 months | 
| Problem Areas in Diabetes Survey | This questionnaire was not assessed as per protocol amendment 7. | Up to 3 months | 
| Hypoglycemia Fear Survey | This questionnaire was not assessed as per protocol amendment 7. | Up to 3 months | 
| Impact of Daily Diabetes Demands | This questionnaire was not assessed as per protocol amendment 7. | Up to 3 months | 
| Bionic Pancreas User Opinion Survey | This questionnaire was not assessed as per protocol amendment 7. | Up to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glucagon, Type 1 diabetes mellitus, Bionic Pancreas, diabetes, iLet, iPhone, Beta Bionics, Anti-hypoglycemia, Glucagon Analog