dasiglucagon: Feasibility Trial Testing the Bionic Pancreas With ZP4207

• Sponsor: Zealand Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02971228
• Collaborator: Massachusetts General Hospital (Other), Beta Bionics, Inc. (Industry)
• Enrollment: 13
• Location: 1
• Arms: 4
• Duration (Months): 7.2
• Patients Per Site Per Month: 1.8

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Insulin Lispro; Drug: ZP4207 (dasiglucagon); Drug: Glucagon; Device: iPhone-based bionic pancreas; Device: iLet-based bionic pancreas	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Bionic Pancreas Feasibility Trial Testing the Bionic Pancreas With ZP4207
• Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: May 24, 2017
• Actual Study Completion Date: Jun 7, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1, Lilly glucagon then ZP4207 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; 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.; Other Names: HumaLOG HumaLOG Cartridge HumaLOG KwikPen ; Drug: ZP4207 (dasiglucagon); A glucagon analog not yet approved by the FDA. Subcutaneous administration in one BP arm.; Other Names: dasiglucagon ; Drug: 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.; Other Names: Glucagon for injection (rDNA original) ; Device: iPhone-based bionic pancreas; An experimental device.
Experimental: Part 1, ZP4207 then Lilly Glucagon 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; 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.; Other Names: HumaLOG HumaLOG Cartridge HumaLOG KwikPen ; Drug: ZP4207 (dasiglucagon); A glucagon analog not yet approved by the FDA. Subcutaneous administration in one BP arm.; Other Names: dasiglucagon ; Drug: 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.; Other Names: Glucagon for injection (rDNA original) ; Device: iPhone-based bionic pancreas; An experimental device.
Experimental: Part 2, Lilly glucagon then ZP4207 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; 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.; Other Names: HumaLOG HumaLOG Cartridge HumaLOG KwikPen ; Drug: ZP4207 (dasiglucagon); A glucagon analog not yet approved by the FDA. Subcutaneous administration in one BP arm.; Other Names: dasiglucagon ; Drug: 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.; Other Names: Glucagon for injection (rDNA original) ; Device: iLet-based bionic pancreas; An experimental device.
Experimental: Part 2, ZP4207 then Lilly Glucagon 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; 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.; Other Names: HumaLOG HumaLOG Cartridge HumaLOG KwikPen ; Drug: ZP4207 (dasiglucagon); A glucagon analog not yet approved by the FDA. Subcutaneous administration in one BP arm.; Other Names: dasiglucagon ; Drug: 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.; Other Names: Glucagon for injection (rDNA original) ; Device: iLet-based bionic pancreas; An experimental device.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. Glycemic Regulation [16 hours]

   Measure glycemic regulation, including hypoglycemia exposure (percent of time spent with continuous glucose monitor [CGM] glucose<60mg/dL)

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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

12. Diabetes Treatment Satisfaction Questionnaire - Status [Up to 3 months]

    This questionnaire was not assessed as per protocol amendment 7.

13. Diabetes Treatment Satisfaction Questionnaire - Change [Up to 3 months]

    This questionnaire was not assessed as per protocol amendment 7.

14. T1-Diabetes Distress Scale [Up to 3 months]

    This questionnaire was not assessed as per protocol amendment 7.

15. Problem Areas in Diabetes Survey [Up to 3 months]

    This questionnaire was not assessed as per protocol amendment 7.

16. Hypoglycemia Fear Survey [Up to 3 months]

    This questionnaire was not assessed as per protocol amendment 7.

17. Impact of Daily Diabetes Demands [Up to 3 months]

    This questionnaire was not assessed as per protocol amendment 7.

18. Bionic Pancreas User Opinion Survey [Up to 3 months]

    This questionnaire was not assessed as per protocol amendment 7.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MGH Diabetes Center	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Zealand Pharma
• Massachusetts General Hospital
• Beta Bionics, Inc.

Investigators

• Principal Investigator: Steven J Russell, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 10, 2017
• Study Protocol - Nov 10, 2017

More Information

Publications

None provided.

• Responsible Party: Zealand Pharma
• ClinicalTrials.gov Identifier: NCT02971228
• Other Study ID Numbers: ZP4207-16051
• First Posted: Nov 22, 2016
• Last Update Posted: Mar 23, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Zealand Pharma: glucagon; Type 1 diabetes mellitus; Bionic Pancreas; diabetes; iLet; iPhone; Beta Bionics; Anti-hypoglycemia; Glucagon Analog
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin Lispro; Glucagon; Pancrelipase; Pancreatin; Glucagon-Like Peptide 1

Study Results

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 Detail	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.

Arm/Group Title	Part 1 Lilly Glucagon or ZP4207	Part 1, Lilly Glucagon Then ZP4207	Part 1, ZP4207 Then Lilly Glucagon	Part 2, ZP4207 Then Lilly Glucagon	Part 2, Lilly Glucagon Then ZP4207
Arm/Group Description	1 patient was enrolled but withdrew prior to treatment with either trial drug	7 patients received Lilly Glucagon then ZP4207 in this treatment sequence (2 withdrew before receiving ZP4207). Insulin Lispro was also administered in both treatment arms. Insulin Lispro: Used to lower blood glucose. Commercially available by prescription and indicated for patients with T1DM, but not for use in a bionic pancreas. Individualized dose based on metabolic needs. ZP4207 (dasiglucagon): A glucagon analog not yet approved by the FDA. Subcutaneous administration. 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. iPhone-based bionic pancreas: An experimental device.	5 patients received ZP4207 then Lilly Glucagon in this treatment sequence. Insulin Lispro was also administered in both treatment arms. Insulin Lispro: Used to lower blood glucose. Commercially available by prescription and indicated for patients with T1DM, but not for use in a bionic pancreas. Individualized dose based on metabolic needs. ZP4207 (dasiglucagon): A glucagon analog not yet approved by the FDA. Subcutaneous administration. 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. iPhone-based bionic pancreas: An experimental device.	Part 2 of the trial was not conducted - see above.	Part 2 of the trial was not conducted - see above.
Period Title: Overall Study
STARTED	1	7	5	0	0
Randomized and Treated	0	7	5	0	0
COMPLETED	0	5	5	0	0
NOT COMPLETED	1	2	0	0	0

Baseline Characteristics

Arm/Group Title	Part 1, All Participants
Arm/Group 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. 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.
Overall Participants	12
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	42.5 (18.47)
Sex: Female, Male (Count of Participants)
Female	6 50%
Male	6 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 8.3%
Not Hispanic or Latino	10 83.3%
Unknown or Not Reported	1 8.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	11 91.7%
More than one race	0 0%
Unknown or Not Reported	1 8.3%
Region of Enrollment (participants) [Number]
United States	12 100%
Body weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	80.28 (18.357)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.36 (5.301)
Diabetes duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.2 (14.72)
HbA1c (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	7.18 (1.462)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} in the iPhone-based Bionic Pancreas with insulin lispro according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon in the iPhone-based Bionic Pancreas with insulin lispro according to a pre-generated randomization scheme. 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. 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.
Measure Participants	10	12
Participants with AEs	8 66.7%	12 NaN
Participants with antibodies	0 0%	0 NaN
Participants with edema infusion site reactions	0 0%	0 NaN
Participants with erythema infusion site reactions	0 0%	0 NaN
Participants with investigations AEs	2 16.7%	2 NaN
Participants with erythrocytes <LLN	0 0%	1 NaN
Participants with hematocrit <LLN	0 0%	1 NaN
Participants with hemoglobin <LLN	0 0%	2 NaN
Participants with lymphocytes <LLN	0 0%	1 NaN
Participants with infusion site pain (VAS)	0 0%	2 NaN
Participants with nausea (VAS)	4 33.3%	2 NaN
Participants with vascular disorders	1 8.3%	1 NaN

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} in the iPhone-based Bionic Pancreas with insulin lispro according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon in the iPhone-based Bionic Pancreas with insulin lispro according to a pre-generated randomization scheme. 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. 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.
Measure Participants	10	12
Baseline	0.00 (0.00)	0.01 (0.0029)
Hour 1	0.00 (0.00)	0.00 (0.00)
Hour 2	0.00 (0.00)	0.00 (0.00)
Hour 3	0.00 (0.00)	0.06 (0.202)
Hour 4	0.00 (0.00)	0.00 (0.00)
Hour 5	0.00 (0.00)	0.00 (0.00)
Hour 6	0.00 (0.00)	0.00 (0.00)
Hour 7	0.00 (0.00)	0.02 (0.058)
Visit end (16 hours)	0.00 (0.00)	0.00 (0.00)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} in the iPhone-based Bionic Pancreas with insulin lispro according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon in the iPhone-based Bionic Pancreas with insulin lispro according to a pre-generated randomization scheme. 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. 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.
Measure Participants	10	12
Baseline	0.00 (0.00)	0.00 (0.00)
Hour 1	0.12 (0.379)	0.00 (0.00)
Hour 2	0.00 (0.00)	0.00 (0.00)
Hour 3	0.11 (0.348)	0.04 (0.144)
Hour 4	0.00 (0.00)	0.00 (0.00)
Hour 5	0.02 (0.063)	0.09 (0.215)
Hour 6	0.29 (0.917)	0.18 (0.522)
Hour 7	0.00 (0.00)	0.00 (0.00)
Visit end (16 hours)	0.11 (0.348)	0.00 (0.00)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} in the iPhone-based Bionic Pancreas with insulin lispro according to pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon in the iPhone-based Bionic Pancreas with insulin lispro according to pre-generated randomization scheme. 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. 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.
Measure Participants	10	12
Mean (Standard Deviation) [percentage of time points]	12.78 (17.262)	17.60 (14.080)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1, ZP4207, Part 1, Lilly Glucagon
	Comments	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.
	Type of Statistical Test	Other
	Comments	A paired t-test was used for the parametric method to compare patients receiving both treatments. A patient was required to have data for both periods to be included in the pre-specified analysis for a given endpoint. Thus, the 2 patients who withdrew from the trial after the Lilly Glucagon treatment before receiving ZP4207 were not included in the analysis.
Statistical Test of Hypothesis	p-Value	0.2518
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.90
	Confidence Interval	(2-Sided) 95%; -19.63 to 5.84
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated mean difference is based on the difference between the mean values for 10 patients in the ZP4207 group (12.78) and the matching 10 patients in the Lilly glucagon group (19.67)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1, ZP4207, Part 1, Lilly Glucagon
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2500
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-8.02
	Confidence Interval	(2-Sided) 95%; -25.85 to 10.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon in the iPhone-based Bionic Pancreas with insulin lispro according to a pre-generated randomization scheme. 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. 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.
Measure Participants	10	12
Mean (Standard Deviation) [Percentage of treatment delivered]	96.73 (4.021)	97.01 (2.851)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1, ZP4207, Part 1, Lilly Glucagon
	Comments	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.
	Type of Statistical Test	Other
	Comments	A paired t-test was used for the parametric method to compare patients receiving both treatments. A patient was required to have data for both periods to be included in the pre-specified analysis for a given endpoint. Thus, the 2 patients who withdrew from the trial after the Lilly Glucagon treatment before receiving ZP4207 were not included in the analysis.
Statistical Test of Hypothesis	p-Value	0.8508
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -3.55 to 2.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1, ZP4207, Part 1, Lilly Glucagon
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.9999
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -4.12 to 3.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	10	12
Mean (Standard Deviation) [Percentage of treatment delivered]	98.36 (1.114)	97.73 (2.051)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1, ZP4207, Part 1, Lilly Glucagon
	Comments	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.
	Type of Statistical Test	Other
	Comments	A paired t-test was used for the parametric method to compare patients receiving both treatments. A patient was required to have data for both periods to be included in the pre-specified analysis for a given endpoint. Thus, the 2 patients who withdrew from the trial after the Lilly Glucagon treatment before receiving ZP4207 were not included in the analysis.
Statistical Test of Hypothesis	p-Value	0.1847
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; -0.36 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1, ZP4207, Part 1, Lilly Glucagon
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0781
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.01 to 3.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	10	12
Mean (Standard Deviation) [percentage of time functioning nominally]	95.41 (1.846)	94.26 (3.966)

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	10	12
Mean (Standard Deviation) [percentage of time functioning nominally]	97.86 (1.125)	96.31 (3.891)

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	10	12
Mean (Standard Deviation) [percentage of recorded values]	97.55 (1.219)	97.94 (1.076)

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	10	12
Mean (Standard Deviation) [mg/dL]	12.6 (4.13)	12.7 (5.43)

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	10	12
Count of Participants [Participants]	9 75%	11 NaN

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	10	12
Count of Participants [Participants]	3 25%	2 NaN

13. Secondary Outcome

Title	Diabetes Treatment Satisfaction Questionnaire - Status
Description	This questionnaire was not assessed as per protocol amendment 7.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

This questionnaire was not assessed as per protocol amendment 7.

Arm/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	0	0

14. Secondary Outcome

Title	Diabetes Treatment Satisfaction Questionnaire - Change
Description	This questionnaire was not assessed as per protocol amendment 7.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

This questionnaire was not assessed as per protocol amendment 7.

Arm/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	0	0

15. Secondary Outcome

Title	T1-Diabetes Distress Scale
Description	This questionnaire was not assessed as per protocol amendment 7.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

This questionnaire was not assessed as per protocol amendment 7.

Arm/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	0	0

16. Secondary Outcome

Title	Problem Areas in Diabetes Survey
Description	This questionnaire was not assessed as per protocol amendment 7.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

This questionnaire was not assessed as per protocol amendment 7.

Arm/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	0	0

17. Secondary Outcome

Title	Hypoglycemia Fear Survey
Description	This questionnaire was not assessed as per protocol amendment 7.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

This questionnaire was not assessed as per protocol amendment 7.

Arm/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	0	0

18. Secondary Outcome

Title	Impact of Daily Diabetes Demands
Description	This questionnaire was not assessed as per protocol amendment 7.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

This questionnaire was not assessed as per protocol amendment 7.

Arm/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	0	0

19. Secondary Outcome

Title	Bionic Pancreas User Opinion Survey
Description	This questionnaire was not assessed as per protocol amendment 7.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

This questionnaire was not assessed as per protocol amendment 7.

Arm/Group Title	Part 1, ZP4207	Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.	In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
Measure Participants	0	0

Adverse Events

Time Frame	Up to 50 days
Arm/Group Title	Part 1, ZP4207		Part 1, Lilly Glucagon
Arm/Group Description	In Part 1, 10 patients received treatment with ZP4207 (dasiglucagon) {experimental drug} with insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. iPhone-based bionic pancreas: An experimental device.		In Part 1, 12 patients received treatment with Lilly glucagon and insulin lispro in the iPhone-based Bionic Pancreas according to a pre-generated randomization scheme. 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. 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.
All Cause Mortality
	Part 1, ZP4207		Part 1, Lilly Glucagon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/12 (0%)
Serious Adverse Events
	Part 1, ZP4207		Part 1, Lilly Glucagon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Part 1, ZP4207		Part 1, Lilly Glucagon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/10 (80%)		12/12 (100%)
Cardiac disorders
Bradycardia	0/10 (0%)	0	1/12 (8.3%)	1
Palpitations	1/10 (10%)	1	0/12 (0%)	0
Ear and labyrinth disorders
Tinnitus	0/10 (0%)	0	1/12 (8.3%)	1
Gastrointestinal disorders
Nausea	5/10 (50%)	5	2/12 (16.7%)	3
Vomiting	1/10 (10%)	1	0/12 (0%)	0
General disorders
Infusion site pain	1/10 (10%)	1	2/12 (16.7%)	5
Asthenia	1/10 (10%)	1	0/12 (0%)	0
Investigations
Neutrophil count increased	2/10 (20%)	3	1/12 (8.3%)	1
White blood cell count increased	2/10 (20%)	2	1/12 (8.3%)	1
Blood glucose decreased	1/10 (10%)	1	1/12 (8.3%)	1
Lymphocyte count increased	1/10 (10%)	1	0/12 (0%)	0
Metabolism and nutrition disorders
Hypoglycemia	6/10 (60%)	14	9/12 (75%)	20
Nervous system disorders
Lethargy	1/10 (10%)	1	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/10 (0%)	0	1/12 (8.3%)	1
Rash	0/10 (0%)	0	1/12 (8.3%)	1
Vascular disorders
Orthostatic hypotension	1/10 (10%)	1	1/12 (8.3%)	1
Hypotension	0/10 (0%)	0	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.