MedPath

Feasibility Trial Testing the Bionic Pancreas With ZP4207

Phase 2
Completed
Conditions
Diabetes Mellitus, Type 1
Interventions
Drug: ZP4207 (dasiglucagon)
Device: iPhone-based bionic pancreas
Device: iLet-based bionic pancreas
Registration Number
NCT02971228
Lead Sponsor
Zealand Pharma
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
13
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Part 1, Lilly glucagon then ZP4207ZP4207 (dasiglucagon)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.
Part 1, Lilly glucagon then ZP4207iPhone-based bionic pancreasIn 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.
Part 1, ZP4207 then Lilly GlucagonZP4207 (dasiglucagon)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.
Part 1, ZP4207 then Lilly GlucagoniPhone-based bionic pancreasIn 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.
Part 2, Lilly glucagon then ZP4207ZP4207 (dasiglucagon)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.
Part 2, Lilly glucagon then ZP4207iLet-based bionic pancreasIn 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.
Part 2, ZP4207 then Lilly GlucagonZP4207 (dasiglucagon)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.
Part 2, ZP4207 then Lilly GlucagoniLet-based bionic pancreasIn 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.
Part 1, Lilly glucagon then ZP4207Insulin LisproIn 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.
Part 1, Lilly glucagon then ZP4207GlucagonIn 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.
Part 1, ZP4207 then Lilly GlucagonInsulin LisproIn 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.
Part 1, ZP4207 then Lilly GlucagonGlucagonIn 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.
Part 2, Lilly glucagon then ZP4207GlucagonIn 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.
Part 2, Lilly glucagon then ZP4207Insulin LisproIn 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.
Part 2, ZP4207 then Lilly GlucagonInsulin LisproIn 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.
Part 2, ZP4207 then Lilly GlucagonGlucagonIn 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.
Primary Outcome Measures
NameTimeMethod
Safety and Tolerability as Measured by Adverse Events, Local Tolerability of Infusion Site Reactions, and Clinical Laboratory ParametersUp 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
NameTimeMethod
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.

Hypoglycemia Fear SurveyUp to 3 months

This questionnaire was not assessed as per protocol amendment 7.

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.

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.

Glycemic Regulation16 hours

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

Average Percent Insulin Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump.16 hours

Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis.

Average Percentage of Time During Which the Bionic Pancreas is Functioning Nominally in All Respects Based on Real-time Continuous Glucose Monitoring (CGM) Data16 hours

Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis.

Average Percentage of Time During Which the Bionic Pancreas is Functioning Nominally With or Without a New CGM Glucose Reading Captured16 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.

Diabetes Treatment Satisfaction Questionnaire - StatusUp to 3 months

This questionnaire was not assessed as per protocol amendment 7.

CGM Reliability Index, Calculated as Percentage of Possible Values Actually Recorded by CGM16 hours

Secondary endpoint of bionic pancreas function, presented by treatment group. The analysis of bionic pancreas function endpoints was on an intention-to-treat basis.

CGM Mean Absolute Relative Difference Versus Time-stamped Blood Glucose (BG) Values From Meter Download16 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.

Number of Patients With Technical Faults Associated With the BP Including Cause and Resolution: Calibration Issues16 hours

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 Issues16 hours

Technical faults related to connectivity issues were listed

Diabetes Treatment Satisfaction Questionnaire - ChangeUp to 3 months

This questionnaire was not assessed as per protocol amendment 7.

T1-Diabetes Distress ScaleUp to 3 months

This questionnaire was not assessed as per protocol amendment 7.

Problem Areas in Diabetes SurveyUp to 3 months

This questionnaire was not assessed as per protocol amendment 7.

Impact of Daily Diabetes DemandsUp to 3 months

This questionnaire was not assessed as per protocol amendment 7.

Bionic Pancreas User Opinion SurveyUp to 3 months

This questionnaire was not assessed as per protocol amendment 7.

Trial Locations

Locations (1)

MGH Diabetes Center

🇺🇸

Boston, Massachusetts, United States

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