Back to resultsFeasibility Trial Testing the Bionic Pancreas With ZP4207 (dasiglucagon)
Primary Purpose
Diabetes Mellitus, Type 1
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Insulin Lispro
ZP4207 (dasiglucagon)
Glucagon
iPhone-based bionic pancreas
iLet-based bionic pancreas
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring glucagon, Type 1 diabetes mellitus, Bionic Pancreas, diabetes, iLet, iPhone, Beta Bionics, Anti-hypoglycemia, Glucagon Analog
Eligibility Criteria
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
Sites / Locations
- MGH Diabetes Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Part 1, Lilly glucagon then ZP4207
Part 1, ZP4207 then Lilly Glucagon
Part 2, Lilly glucagon then ZP4207
Part 2, ZP4207 then Lilly Glucagon
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Glycemic Regulation
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.
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.
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
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
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
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
Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis.
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.
Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Connectivity Issues
Technical faults related to connectivity issues were listed
Diabetes Treatment Satisfaction Questionnaire - Status
This questionnaire was not assessed as per protocol amendment 7.
Diabetes Treatment Satisfaction Questionnaire - Change
This questionnaire was not assessed as per protocol amendment 7.
T1-Diabetes Distress Scale
This questionnaire was not assessed as per protocol amendment 7.
Problem Areas in Diabetes Survey
This questionnaire was not assessed as per protocol amendment 7.
Hypoglycemia Fear Survey
This questionnaire was not assessed as per protocol amendment 7.
Impact of Daily Diabetes Demands
This questionnaire was not assessed as per protocol amendment 7.
Bionic Pancreas User Opinion Survey
This questionnaire was not assessed as per protocol amendment 7.
Full Information
NCT ID
NCT02971228
First Posted
November 3, 2016
Last Updated
February 26, 2021
Sponsor
Zealand Pharma
Collaborators
Massachusetts General Hospital, Beta Bionics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02971228
Brief Title
Feasibility Trial Testing the Bionic Pancreas With ZP4207
Acronym
dasiglucagon
Official Title
The Bionic Pancreas Feasibility Trial Testing the Bionic Pancreas With ZP4207
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
November 2016 (undefined)
Primary Completion Date
May 24, 2017 (Actual)
Study Completion Date
June 7, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zealand Pharma
Collaborators
Massachusetts General Hospital, Beta Bionics, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
Keywords
glucagon, Type 1 diabetes mellitus, Bionic Pancreas, diabetes, iLet, iPhone, Beta Bionics, Anti-hypoglycemia, Glucagon Analog
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1, Lilly glucagon then ZP4207
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 1, ZP4207 then Lilly Glucagon
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2, Lilly glucagon then ZP4207
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2, ZP4207 then Lilly Glucagon
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Insulin Lispro
Other Intervention Name(s)
HumaLOG, HumaLOG Cartridge, HumaLOG KwikPen
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
ZP4207 (dasiglucagon)
Other Intervention Name(s)
dasiglucagon
Intervention Description
A glucagon analog not yet approved by the FDA. Subcutaneous administration in one BP arm.
Intervention Type
Drug
Intervention Name(s)
Glucagon
Other Intervention Name(s)
Glucagon for injection (rDNA original)
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
iPhone-based bionic pancreas
Intervention Description
An experimental device.
Intervention Type
Device
Intervention Name(s)
iLet-based bionic pancreas
Intervention Description
An experimental device.
Primary Outcome Measure Information:
Title
Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory Parameters
Description
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
Secondary Outcome Measure Information:
Title
Pain Measured on a Visual Analog Scale (VAS)
Description
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
Title
Nausea Measured on a Visual Analog Scale (VAS)
Description
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
Title
Glycemic Regulation
Description
Measure glycemic regulation, including hypoglycemia exposure (percent of time spent with continuous glucose monitor [CGM] glucose<60mg/dL)
Time Frame
16 hours
Title
Average Percent Glucagon Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump.
Description
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
Title
Average Percent Insulin Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump.
Description
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
Title
Average Percentage of Time During Which the Bionic Pancreas is Functioning Nominally in All Respects Based on Real-time Continuous Glucose Monitoring (CGM) Data
Description
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
Title
Average Percentage of Time During Which the Bionic Pancreas is Functioning Nominally With or Without a New CGM Glucose Reading Captured
Description
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
Title
CGM Reliability Index, Calculated as Percentage of Possible Values Actually Recorded by CGM
Description
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
Title
CGM Mean Absolute Relative Difference Versus Time-stamped Blood Glucose (BG) Values From Meter Download
Description
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
Title
Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Calibration Issues
Description
Technical faults in terms of calibration issues were listed by patient.
Time Frame
16 hours
Title
Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Connectivity Issues
Description
Technical faults related to connectivity issues were listed
Time Frame
16 hours
Title
Diabetes Treatment Satisfaction Questionnaire - Status
Description
This questionnaire was not assessed as per protocol amendment 7.
Time Frame
Up to 3 months
Title
Diabetes Treatment Satisfaction Questionnaire - Change
Description
This questionnaire was not assessed as per protocol amendment 7.
Time Frame
Up to 3 months
Title
T1-Diabetes Distress Scale
Description
This questionnaire was not assessed as per protocol amendment 7.
Time Frame
Up to 3 months
Title
Problem Areas in Diabetes Survey
Description
This questionnaire was not assessed as per protocol amendment 7.
Time Frame
Up to 3 months
Title
Hypoglycemia Fear Survey
Description
This questionnaire was not assessed as per protocol amendment 7.
Time Frame
Up to 3 months
Title
Impact of Daily Diabetes Demands
Description
This questionnaire was not assessed as per protocol amendment 7.
Time Frame
Up to 3 months
Title
Bionic Pancreas User Opinion Survey
Description
This questionnaire was not assessed as per protocol amendment 7.
Time Frame
Up to 3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven J Russell, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
MGH Diabetes Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Feasibility Trial Testing the Bionic Pancreas With ZP4207
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