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| ID | Type | Description | Link |
|---|---|---|---|
| 1R44DK107114 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
| Xeris Pharmaceuticals | INDUSTRY |
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To assess the efficacy of a closed loop glucagon system to prevent and treat hypoglycemia occurring in patients with Post-Bariatric Hypoglycemia (PBH) in response to meals and exercise.
A control system for sensor-guided delivery was previously developed and tested in a Proof-of-Concept (POC) study in a clinical research setting during 9 mixed meal tolerance tests in 8 unique patients with severe hypoglycemia following bariatric surgery. This optimized algorithm will now be implemented to deliver stable glucagon in a closed-loop system.
A randomized, placebo-controlled, masked trial will be conducted to assess the efficacy of the closed loop system to prevent and treat hypoglycemia occurring in patients with PBH in response to meals (part 1). Part 2 will test whether the closed loop system can also prevent and treat hypoglycemia in patients with PBH in response to exercise. A manufacturing program from our collaborating team at Xeris Pharmaceuticals will continue to produce supplies of glucagon for the clinical trial in a current good manufacturing practice (cGMP) facility, with continued shelf-life stability testing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study drug (glucagon) first, placebo second | Other | Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session. |
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| Placebo first, study drug (glucagon) second | Other | Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| glucagon | Drug | novel, stable non-aqueous glucagon formulation provided by Xeris Pharmaceuticals |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <65 mg/dL | A primary endpoint for this study is the prevention of meal provoked hypoglycemia, defined as sensor glucose levels below <65 mg/dl, comparing study drug to control. | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <65 mg/dL | A primary endpoint for this study is prevention of meal provoked hypoglycemia, defined as plasma glucose levels below <65 mg/dl, comparing study drug to control | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <60 mg/dL | Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below <60 mg/dl, comparing vehicle to control | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mary E Patti, MD | Joslin Diabetes Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Joslin Diabetes Center | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31714583 | Background | Mulla CM, Zavitsanou S, Laguna Sanz AJ, Pober D, Richardson L, Walcott P, Arora I, Newswanger B, Cummins MJ, Prestrelski SJ, Doyle FJ, Dassau E, Patti ME. A Randomized, Placebo-Controlled Double-Blind Trial of a Closed-Loop Glucagon System for Postbariatric Hypoglycemia. J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1260-71. doi: 10.1210/clinem/dgz197. |
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Between September 2017 and August 2018, 23 individuals were screened and 18 enrolled (consort diagram, Fig. 2). Two participants withdrew before the first mixed-meal study visit because of inability to obtain adequate intravenous access.
Participants with a history of Roux-en-Y gastric bypass (RYGB) and post-bariatric hypoglycemia (PBH) with neuroglycopenia, uncontrolled on medical nutrition therapy and medications, were recruited from the Joslin Diabetes Center hypoglycemia clinic and other endocrine clinics in the region.
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| ID | Title | Description |
|---|---|---|
| FG000 | Study Drug (Glucagon) First, Then Placebo (Randomized, Double-blind, Crossover Design) | Each subject underwent two mixed meal tolerance tests, and was randomized to receive either glucagon or placebo during the first testing session (opposite treatment was given during the second testing session). These participants received glucagon first, and then the placebo at the second visit. A participant could receive 2 doses of the study drug or placebo at each study visit. Glucagon: novel, stable, non-aqueous glucagon formulation provided by Xeris Pharmaceuticals. Closed loop glucagon pump: a novel closed-loop glucagon system (CLG) incorporating a novel, stable non-aqueous glucagon formulation together with an infusion pump system (Omnipod) guided by real-time continuous glucose monitoring (Dexcom) that is triggered by a hypoglycemia alert algorithm. |
| FG001 | Placebo First, Then Study Drug (Glucagon) Second (Randomized, Double-blind, Crossover Design) | Each subject underwent two mixed meal tolerance tests performed. Each was randomized to receive either glucagon or matched placebo during the first testing session. The opposite treatment was given during the second testing session. Both participants and the study team were blinded to the intervention being used during each session. These participants received placebo at the fist visit, and the study drug glucagon at the second visit. A participant could receive 2 doses of the study drug or placebo at each study visit. Closed loop glucagon pump: a novel closed-loop glucagon system (CLG) incorporating a novel, stable non-aqueous glucagon formulation (for this group - they received placebo first) together with an infusion pump system (Omnipod) guided by real-time continuous glucose monitoring (Dexcom) that is triggered by a hypoglycemia alert algorithm. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Demographic Information for 12 Enrolled Participants Who Completed 2 Mixed-Meal Study Visits and Were Included in the Analysis
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment Arm / Control Arm (Randomized, Double-Blind, Placebo-Controlled Crossover Design) | Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. The opposite treatment will be given during the second testing session. Both participants and the study team will be blinded to the intervention being used during each session. glucagon: novel, stable non-aqueous glucagon formulation provided by Xeris Pharmaceuticals Closed loop glucagon pump: a novel closed-loop glucagon system (CLG) incorporating a novel, stable non-aqueous glucagon formulation together with an infusion pump system (Omnipod) guided by real-time continuous glucose monitoring (Dexcom) that is triggered by a hypoglycemia alert algorithm. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <65 mg/dL | A primary endpoint for this study is the prevention of meal provoked hypoglycemia, defined as sensor glucose levels below <65 mg/dl, comparing study drug to control. | 12 Enrolled Participants Completed 2 Mixed-Meal Study Visits and Were Included in the Analysis | Posted | Number | participants | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
|
Adverse event data were collected over the the duration of each individuals participation, a 2 to 3 week period of time, encompassing the time of enrollment, to the completion of visit 5.
Regarding discrepancy between participant flow and number of participants at risk: 18 participants enrolled, however two participants withdrew before the first mixed-meal study visit because of inability to obtain adequate intravenous access. Sixteen participants completed the first mixed-meal study visit; 12 participants completed both mixed meal study visits and were included in analysis.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Arm and Control Arm (Randomized, Double-Blind, Placebo-Controlled Crossover Design) | Each subject had two mixed meal tolerance tests performed. Each was randomized to receive either glucagon or matched placebo during the first testing session. The opposite treatment was given during the second testing session. Both participants and the study team were blinded to the intervention being used during each session. glucagon: novel, stable non-aqueous glucagon formulation provided by Xeris Pharmaceuticals Closed loop glucagon pump: a novel closed-loop glucagon system (CLG) incorporating a novel, stable non-aqueous glucagon formulation together with an infusion pump system (Omnipod) guided by real-time continuous glucose monitoring (Dexcom) that is triggered by a hypoglycemia alert algorithm. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypokalemia | Metabolism and nutrition disorders | Non-systematic Assessment | Pt was not randomized. hypokalemia discovered during screening visit; admitted to hospital. resolved without sequelae. not related to study protocol or intervention. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperkalemia at screening visit | Metabolism and nutrition disorders | Non-systematic Assessment | Discovered at screening visit. No treatment. Labs were repeated at Visit 2, potassium was within reference range. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mary Elizabeth Patti, MD | Joslin Diabetes Center | (617) 309-2635 | MaryElizabeth.Patti@joslin.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 6, 2018 | Sep 28, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D005934 | Glucagon |
| ID | Term |
|---|---|
| D052336 | Proglucagon |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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| Harvard University |
| OTHER |
A randomization scheme will be devised to assign half the subjects to receive glucagon during their first challenge visit and the other half to receive vehicle during their first challenge visit. At their second challenge subjects will be assigned to the product not received during their first challenge. The label will include a subject randomization number and information as to which vial should be administered during the first challenge and which should be administered during the second challenge.
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Study medication will be provided in vials which are labeled with randomization information only but not contents of vial.
| Closed loop glucagon pump | Device | a novel closed-loop glucagon system (CLG) incorporating a novel, stable non-aqueous glucagon formulation together with an infusion pump system (Omnipod) guided by real-time continuous glucose monitoring (Dexcom) that is triggered by a hypoglycemia alert algorithm. |
|
| Number of Participants With Rebound Hyperglycemia (Defined as Glucose Levels Above 180 mg/dl). | Compare outcomes for glucagon versus vehicle infusions for prevention of rebound hyperglycemia (defined as glucose levels above 180 mg/dl). | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge will be conducted within two weeks of the first. |
| Number of Participants With Hypoglycemia Rescue Administered | Protocol-specified rescue delivery of IV glucose was performed if plasma glucose <55 mg/dL and/or significant neuroglycopenia developed. | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <60 mg/dL | Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below <60 mg/dl, comparing vehicle to control | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <55 mg/dL | Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below <55 mg/dl, comparing vehicle to control | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <55 mg/dL | Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below <55 mg/dl, comparing vehicle to control | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Percent Time Plasma Glucose in Range After the Final Dose of Study Drug or Vehicle, Which Was Either 1 or 2 Doses Depending on Patient Response | Compare outcomes for glucagon versus vehicle infusions for percent time plasma glucose in range (180-65mg/dL) after the final dose, which was either 1 or 2 doses depending on patient response | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Percent Time Sensor Glucose in Range After Drug Delivery After the Final Dose of Study Drug or Vehicle, Which Was Either 1 or 2 Doses Depending on Patient Response | Compare outcomes for glucagon versus vehicle infusions for percent time sensor glucose in range (180-65mg/dL) after the final dose, which was either 1 or 2 doses depending on patient response | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Meal Provoked Nadir Plasma Glucose | Nadir plasma glucose (mg/dl) during meal testing, comparing vehicle to control | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Meal Provoked Nadir Sensor Glucose | Nadir sensor glucose (mg/dl) during meal testing, comparing vehicle to control | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Time to Nadir Plasma Glucose After Mixed Meal (Min) | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Time to Nadir Sensor Glucose After Mixed Meal (Min) | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Time to Alarm During Mixed Meal Testing (Minutes) | Time to alarm represents the time for the first alarm to occur during mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm. | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Time to Delivery (Min) | Time to delivery (min) of study drug during mixed meal testing | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Sensor Glucose at Time of Alarm 1 During Mixed Meal Testing (mg/dL) | This is the sensor glucose at which time the first alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm. | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Capillary Glucose at Time of Alarm 1 During Mixed Meal Testing (mg/dL) | This is the capillary glucose at which time the first alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm. | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Sensor Glucose at Time of Alarm 2 During Mixed Meal Testing (mg/dL) | This is the sensor glucose at which time the second alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm. | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Capillary Glucose at Time of Alarm 2 During Mixed Meal Testing (mg/dL) | This is the capillary glucose at which time the second alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm. | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
| Pain Score at Time of First Dose Delivery of Study Drug, Versus Pain Score at Time of First Dose Delivery of Placebo (Comparing First Delivery Pain Scores for Visit Where Participant Received Study Drug vs. Visit Where Participant Received Placebo). | Pain score was assessed verbally, 1 is the least pain (none), 10 is the most severe pain. Pain score at the time of the first administration was compared for the visit where the participant received the study drug vs. the visit where the participant received the placebo. A participant could receive 2 doses of the study drug or placebo at each visit. All 12 participants completed both the study drug phase and the placebo phase. The pain scores for the first administration of study drug vs. first administration of placebo for these two visits were compared. Whether the participant was assigned to the study drug glucagon (vs. placebo) at the first or second MMTT was determined by randomization. | The two study visits where participants were administered either study drug or placebo took place over 2 weeks (there was a 1 to 2 week washout period between visits). |
| Pain Score at Time of Second Dose Delivery of Study Drug, Versus Pain Score at Time of Second Dose Delivery of Placebo (Comparing Second Delivery Pain Scores for Visit Where Participant Received Study Drug vs. Visit Where Participant Received Placebo). | Pain score was assessed verbally, 1 is the least pain (none), 10 is the most severe pain. Pain score at the time of the second administration was compared for the visit where the participant received the study drug vs. the visit where the participant received the placebo. A participant could receive 2 doses of the study drug or placebo at each visit. All 12 participants completed both the study drug phase and the placebo phase. The pain scores from the second administration of study drug vs. second administration of placebo for these two visits were compared. Whether the participant was assigned to the study drug glucagon (vs. placebo) at the first or second MMTT was determined by randomization. | The two study visits where participants were administered either study drug or placebo took place over 2 weeks (there was a 1 to 2 week washout period between visits). |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| BMI | Mean | Standard Deviation | kg/m^2 |
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| Years since surgery | Mean | Standard Deviation | years |
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| Years from surgery to neuroglycopenia | Median | Inter-Quartile Range | years |
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| HbA1c | Mean | Standard Deviation | percent |
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| On any anti-hypoglycemic medications | Count of Participants | Participants |
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| Treated with acarbose | Count of Participants | Participants |
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| Treated with diazoxide | Count of Participants | Participants |
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| Treated with octreotide | Count of Participants | Participants |
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| Treated with pramlintide | Count of Participants | Participants |
|
| OG001 | Placebo / Control Phase | This phase represents when the participant received the placebo. A participant could receive 2 doses of the placebo at this visit. Each subject had two mixed meal tolerance tests performed. Each was randomized to receive either glucagon or matched placebo during the first testing session. The opposite treatment was given during the second testing session after a 1-2 week washout period. Both participants and the study team were blinded to the intervention being used during each session. Closed loop glucagon pump: a novel closed-loop glucagon system (CLG) incorporating a novel, stable non-aqueous glucagon formulation (for this phase containing placebo vs. glucagon) together with an infusion pump system (Omnipod) guided by real-time continuous glucose monitoring (Dexcom) that is triggered by a hypoglycemia alert algorithm. |
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| Primary | Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <65 mg/dL | A primary endpoint for this study is prevention of meal provoked hypoglycemia, defined as plasma glucose levels below <65 mg/dl, comparing study drug to control | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. | Posted | Count of Participants | Participants | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <60 mg/dL | Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below <60 mg/dl, comparing vehicle to control | Posted | Count of Participants | Participants | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Number of Participants With Rebound Hyperglycemia (Defined as Glucose Levels Above 180 mg/dl). | Compare outcomes for glucagon versus vehicle infusions for prevention of rebound hyperglycemia (defined as glucose levels above 180 mg/dl). | Posted | Count of Participants | Participants | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge will be conducted within two weeks of the first. |
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| Secondary | Number of Participants With Hypoglycemia Rescue Administered | Protocol-specified rescue delivery of IV glucose was performed if plasma glucose <55 mg/dL and/or significant neuroglycopenia developed. | Posted | Count of Participants | Participants | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <60 mg/dL | Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below <60 mg/dl, comparing vehicle to control | Posted | Count of Participants | Participants | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <55 mg/dL | Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below <55 mg/dl, comparing vehicle to control | Posted | Count of Participants | Participants | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <55 mg/dL | Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below <55 mg/dl, comparing vehicle to control | Posted | Count of Participants | Participants | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Percent Time Plasma Glucose in Range After the Final Dose of Study Drug or Vehicle, Which Was Either 1 or 2 Doses Depending on Patient Response | Compare outcomes for glucagon versus vehicle infusions for percent time plasma glucose in range (180-65mg/dL) after the final dose, which was either 1 or 2 doses depending on patient response | Posted | Mean | Standard Error | percentage of time | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Percent Time Sensor Glucose in Range After Drug Delivery After the Final Dose of Study Drug or Vehicle, Which Was Either 1 or 2 Doses Depending on Patient Response | Compare outcomes for glucagon versus vehicle infusions for percent time sensor glucose in range (180-65mg/dL) after the final dose, which was either 1 or 2 doses depending on patient response | Posted | Mean | Standard Error | percentage of time | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Meal Provoked Nadir Plasma Glucose | Nadir plasma glucose (mg/dl) during meal testing, comparing vehicle to control | Posted | Mean | Standard Error | mg/dL | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Meal Provoked Nadir Sensor Glucose | Nadir sensor glucose (mg/dl) during meal testing, comparing vehicle to control | Posted | Mean | Standard Error | mg/dL | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Time to Nadir Plasma Glucose After Mixed Meal (Min) | Posted | Mean | Standard Error | minutes | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Time to Nadir Sensor Glucose After Mixed Meal (Min) | Posted | Mean | Standard Error | minutes | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Time to Alarm During Mixed Meal Testing (Minutes) | Time to alarm represents the time for the first alarm to occur during mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm. | Posted | Mean | Standard Error | minutes | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Time to Delivery (Min) | Time to delivery (min) of study drug during mixed meal testing | Posted | Mean | Standard Error | minutes | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Sensor Glucose at Time of Alarm 1 During Mixed Meal Testing (mg/dL) | This is the sensor glucose at which time the first alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm. | Posted | Mean | Standard Error | mg/dL | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Capillary Glucose at Time of Alarm 1 During Mixed Meal Testing (mg/dL) | This is the capillary glucose at which time the first alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm. | Posted | Mean | Standard Error | mg/dL | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Sensor Glucose at Time of Alarm 2 During Mixed Meal Testing (mg/dL) | This is the sensor glucose at which time the second alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm. | Posted | Mean | Standard Error | mg/dL | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Capillary Glucose at Time of Alarm 2 During Mixed Meal Testing (mg/dL) | This is the capillary glucose at which time the second alarm occurred during the mixed meal testing. Alarms are triggered by hypoglycemia (sensor glucose < 65 mg/dL), or by the algorithm predicting that hypoglycemia will occur in less than 30 minutes (taking into account current sensor glucose level (between 65-150 mg/dL) and the rate of change of a rapidly falling sensor glucose level). In the latter case, the alarm is activated even if glucose levels are within the normoglycemic range to allow early detection and response. During both glucagon and vehicle treatment visits, all participants received either 300 μg of glucagon or the equivalent volume of vehicle with the first alarm. | Posted | Mean | Standard Error | mg/dL | Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first. |
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| Secondary | Pain Score at Time of First Dose Delivery of Study Drug, Versus Pain Score at Time of First Dose Delivery of Placebo (Comparing First Delivery Pain Scores for Visit Where Participant Received Study Drug vs. Visit Where Participant Received Placebo). | Pain score was assessed verbally, 1 is the least pain (none), 10 is the most severe pain. Pain score at the time of the first administration was compared for the visit where the participant received the study drug vs. the visit where the participant received the placebo. A participant could receive 2 doses of the study drug or placebo at each visit. All 12 participants completed both the study drug phase and the placebo phase. The pain scores for the first administration of study drug vs. first administration of placebo for these two visits were compared. Whether the participant was assigned to the study drug glucagon (vs. placebo) at the first or second MMTT was determined by randomization. | Posted | Mean | Standard Error | pain score | The two study visits where participants were administered either study drug or placebo took place over 2 weeks (there was a 1 to 2 week washout period between visits). |
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| Secondary | Pain Score at Time of Second Dose Delivery of Study Drug, Versus Pain Score at Time of Second Dose Delivery of Placebo (Comparing Second Delivery Pain Scores for Visit Where Participant Received Study Drug vs. Visit Where Participant Received Placebo). | Pain score was assessed verbally, 1 is the least pain (none), 10 is the most severe pain. Pain score at the time of the second administration was compared for the visit where the participant received the study drug vs. the visit where the participant received the placebo. A participant could receive 2 doses of the study drug or placebo at each visit. All 12 participants completed both the study drug phase and the placebo phase. The pain scores from the second administration of study drug vs. second administration of placebo for these two visits were compared. Whether the participant was assigned to the study drug glucagon (vs. placebo) at the first or second MMTT was determined by randomization. | Posted | Mean | Standard Error | pain score | The two study visits where participants were administered either study drug or placebo took place over 2 weeks (there was a 1 to 2 week washout period between visits). |
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| 0 |
| 18 |
| 1 |
| 18 |
| 16 |
| 18 |
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| MCH above normal limit of refrence range at screening visit. | Blood and lymphatic system disorders | Non-systematic Assessment | No treatment. Complete blood count (CBC) repeated on 2/28/2018.Labs were acceptable to begin study visit. |
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| WBC above normal limit of reference range at screening visit | Blood and lymphatic system disorders | Non-systematic Assessment | No treatment. CBC repeated on 2/28/2018.Labs were acceptable to begin study visit. |
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| Headache prior to start of MMTT | General disorders | Non-systematic Assessment | Not related to study drug or placebo as was present upon arrival. |
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| Tiredness prior to start of MMTT | General disorders | Non-systematic Assessment | Not related to study drug or placebo as was present upon arrival to study visit. |
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| Nausea after intake of mixed meal (prior to glucagon OR placebo) | Gastrointestinal disorders | Non-systematic Assessment | Related to mixed meal tolerance test (MMTT). Resolved without sequelae. |
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| Headache after intake of mixed meal (prior to glucagon OR placebo) | General disorders | Non-systematic Assessment | Related to MMTT. Resolved without sequelae. |
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| Palpitations after intake of mixed meal (prior to study drug OR placebo) | Cardiac disorders | Non-systematic Assessment | Related to MMTT. Resolved without sequelae. |
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| Emesis after intake of mixed meal (prior to study drug OR placebo) | Gastrointestinal disorders | Non-systematic Assessment | Adverse event (AE) linked to meal tolerance test, especially in patient population under study. Required ER evaluation in 1 participant due to repetitive vomiting. All resolved. |
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| Feeling cold / chills after intake of mixed meal (prior to study drug OR placebo) | General disorders | Non-systematic Assessment | Related to MMTT, resolved. |
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| Feeling hot / warm after intake of mixed meal (prior to study drug or placebo) | General disorders | Non-systematic Assessment | AE linked to MMTT. Resolved. |
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| Thirsty after intake of mixed meal (prior to study drug OR placebo) | General disorders | Non-systematic Assessment | Related to MMTT. Resolved. |
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| Tiredness after intake of mixed meal (prior to study drug OR placebo) | General disorders | Non-systematic Assessment | AE linked to MMTT. Resolved. |
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| Stomach ache / cramping after intake of mixed meal (prior to study drug OR placebo) | Gastrointestinal disorders | Non-systematic Assessment | AE linked to MMTT. Resolved. |
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| Bloated / uncomfortably full after intake of mixed meal (prior to study drug OR placebo) | Gastrointestinal disorders | Non-systematic Assessment | AE linked to MMTT. Resolved. |
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| Blurry vision after intake of mixed meal (prior to study drug OR placebo) | Eye disorders | Non-systematic Assessment | AE linked to MMTT. Resolved. |
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| Tingling (paresthesia) in shoulders after intake of mixed meal (prior to study drug or placebo) | General disorders | Non-systematic Assessment | Related to MMTT. Resolved. |
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| Tingling (paresthesia) around the mouth after intake of mixed meal (prior to study drug or placebo) | General disorders | Non-systematic Assessment | AE linked to MMTT. Resolved. |
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| Dizzy after intake of mixed meal (prior to study drug OR placebo) | General disorders | Non-systematic Assessment | AE linked to MMTT. Resolved. |
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| Feeling unwell ("icky... drunk") after intake of mixed meal (prior to study drug OR placebo) | General disorders | Non-systematic Assessment | AE linked MMTT. Resolved. |
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| Tearful after intake of mixed meal (prior to study drug OR placebo) | General disorders | Non-systematic Assessment | AE linked to MMTT. Resolved. |
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| Pain at pump site during MMTT (prior to delivery of study drug or placebo) | General disorders | Non-systematic Assessment | Related to study device. Resolved. |
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| Pruritis at pump insertion site during MMTT (prior to delivery of study drug or placebo) | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Irritation / pain at IV site with IV administration of dextrose | General disorders | Non-systematic Assessment | AE related to administration of D50 at placebo visit. Resolved. |
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| Tearful when IV dextrose (D50) administered | General disorders | Non-systematic Assessment | Related to MMTT & hypoglycemia, at visit where placebo was administered. Resolved. |
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| Hypoglycemia during study (MMTT) | Endocrine disorders | Non-systematic Assessment | Related to MMTT in population understudy. Resolved. |
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| Erythema at site of CGM sensor | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Related to continuous glucose monitoring (CGM) device (sensor or adhesive). Resolved. |
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| Hematoma under CGM sensor | Skin and subcutaneous tissue disorders | Non-systematic Assessment | AE related to CGM sensor device. |
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| Burning pain / pricking at pump site after alarm (placebo visit) | General disorders | Non-systematic Assessment | AE linked to placebo and study device. |
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| Buring pain at pump site after alarm (glucagon visit) | General disorders | Non-systematic Assessment |
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| Erythema at pump infusion site (placebo visit) | Skin and subcutaneous tissue disorders | Non-systematic Assessment | AE related to study device and placebo. |
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| Erythema at pump infusion site (glucagon visit) | Skin and subcutaneous tissue disorders | Non-systematic Assessment | AE related to study device and study drug - glucagon. |
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| Edema at pump infusion site (placebo visit) | Skin and subcutaneous tissue disorders | Non-systematic Assessment | AE related to study device and placebo. |
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| Edema at pump infusion site (glucagon visit) | Skin and subcutaneous tissue disorders | Non-systematic Assessment | AE related to study device and study drug - glucagon. |
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| Feeling hot after alarm (glucagon visit) | General disorders | Non-systematic Assessment | AE linked to MMTT, hypoglycemia, and delivery of study drug. |
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| Feeling hot after alarm (placebo visit) | General disorders | Non-systematic Assessment | AE linked to MMTT, hypoglycemia, and delivery of placebo. |
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| Thirsty after alarm (placebo visit) | Endocrine disorders | Non-systematic Assessment | AE linked to MMTT, hypoglycemia, and delivery of placebo. |
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| Nausea after alarm (glucagon visit) | Gastrointestinal disorders | Non-systematic Assessment | AE linked to MMTT, hypoglycemia, and delivery of study drug. |
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| Vomiting after alarm (glucagon visit) | Gastrointestinal disorders | Non-systematic Assessment | Participant also vomited during mixed meal, prior to study drug administration. AE linked to MMTT, hypoglycemia, and delivery of study drug. |
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| Headace after alarm (glucagon visit) | General disorders | Non-systematic Assessment | Both participants with headache following alarm also had headache prior to the alarm during mixed meal testing. AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Tearful during alarm (placebo visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and placebo. |
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| Confusion after alarm (placebo visit) | Nervous system disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and placebo. |
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| Confusion after alarm (glucagon visit) | Nervous system disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Dizzy / lightheaded after alarm (glucagon visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Low blood pressure after alarm (placebo visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and placebo. |
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| Tiredness after alarm (glucagon visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Tiredness after alarm (placebo visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and placebo. |
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| Blurry vision after alarm (placebo visit) | Eye disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and placebo. |
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| Blurry vision after alarm (glucagon visit) | Eye disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Bowel urgency after alarm (glucagon visit) | Gastrointestinal disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Bowel movement after alarm (placebo visit) | Gastrointestinal disorders | Non-systematic Assessment | AE related to MMTT, and placebo. |
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| Stomach cramping / pain after alarm (placebo visit) | Gastrointestinal disorders | Non-systematic Assessment | AE related to MMTT and placebo. |
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| Lower extremity cramping after alarm (glucagon visit) | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | Legs and toes cramping. AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Pale after alarm (placebo visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and placebo. |
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| Speech slowed after alarm (placebo visit) | Nervous system disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and placebo. |
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| Nausea prior to lunch (glucagon visit) | Gastrointestinal disorders | Non-systematic Assessment | This participant was also nauseous after intake of mixed meal, prior to receiving the study drug. AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Weakness prior to lunch (glucagon visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Feeling hot prior to lunch (glucagon visit) | General disorders | Non-systematic Assessment | This participant also felt hot following intake of mixed meal, prior to delivery of study drug. AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Feeling hot after lunch (placebo visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, placebo. |
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| Tiredness after lunch (glucagon visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Tiredness after lunch (placebo visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and placebo. |
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| Feeling cold after lunch (glucagon visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Headache after lunch (glucagon visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Stomach pains after lunch (glucagon visit) | Gastrointestinal disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Nausea after lunch (glucagon visit) | Gastrointestinal disorders | Non-systematic Assessment | Participant also had nausea after intake of mixed meal, prior to delivery of study drug. AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Vomiting after lunch (glucagon visit) | Gastrointestinal disorders | Non-systematic Assessment | This participant had nausea which started after intake of mixed meal, prior to study drug administration. AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Shaky following lunch (glucagon visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Ears ringing after lunch | General disorders | Non-systematic Assessment | AE related to MMTT. Resolved. |
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| Foggy feeling after lunch (glucagon visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Hypoglycemia following lunch (gluagon visit) | Endocrine disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Hypoglycemia following lunch (placebo visit) | Endocrine disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and placebo. |
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| Back pain after lunch (placebo visit) | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | Not related. Participant with chronic back pain. |
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| Dry mouth following alarm (glucagon visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Pruritis at pump site after alarm (placebo visit) | Skin and subcutaneous tissue disorders | Non-systematic Assessment | AE related to study device and placebo. |
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| Dizzy after discharge (placebo visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and placebo. |
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| Hypoglycemia after dinner the night following the study visit (glucagon visit) | Endocrine disorders | Non-systematic Assessment | Possibly related to study visit and study drug (glucagon). |
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| Tiredness day after study visit (placebo visit) | Gastrointestinal disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and placebo. |
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| Tiredness day after study visit (glucagon visit) | General disorders | Non-systematic Assessment | AE related to MMTT, hypoglycemia, and study drug - glucagon. |
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| Migraine headache one night following study visit (placebo visit) | Nervous system disorders | Non-systematic Assessment | Possibly related to MMTT, hypoglycemia, and placebo. |
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| Erythema a pump infusion site 1 day following discharge (glucagon visit) | Skin and subcutaneous tissue disorders | Non-systematic Assessment | 2" diameter corresponding with area of the adhesive. AE related to pump device adhesive. This participant had erythema as well documented on the day of the study visit. Resolved. |
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Not provided
Not provided
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |