Mini-Dose Glucagon to Treat Non-Severe Hypoglycemia

Study Overview
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Brief Summary
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The purpose of this study is to determine if a small dose of glucagon (mini-dose glucagon) is effective for the treatment of non-severe hypoglycemia in adults with type 1 diabetes (T1D).

Detailed Description
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There are three phases included in this study: (1) Pre-crossover Trial Run-in Phase, (2) Randomized Clinical Trial (RCT) Crossover Trial Phase, and (3) Post-Crossover Trial Extension Phase. Run-in Phase: Prior to commencing the crossover trial, study enrollment will begin with a 2 week run-in phase to assess hypoglycemia eligibility and compliance. Crossover Trial Phase: The Crossover Trial Phase will consist of two (3-week) periods. The Crossover Trial Phase will include up to 24 participants who complete these study periods. Participants who do not complete both periods or who do not have at least one event during both periods may be replaced. During the Crossover Trial Phase participants will be randomized into two groups: (1) Group A will use mini-dose glucagon in period 1 and oral glucose tablets in period 2 and (2) Group B will use oral glucose tablets in period 1 and mini-dose glucagon in period 2. Each group with follow the applicable treatment arm according to their randomized group. Extension Phase: The Post-Crossover Trial phase will commence upon completion of the second 3-week period of the Crossover Trial Phase. Participants will have a 3 week phase during which time they will decide whether to use mini-dose glucagon or glucose tablets to treat each non-severe hypoglycemic event or to prevent hypoglycemia.

Official Title
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Mini-Dose Glucagon for Adults With Type 1 Diabetes: A Study to Assess the Efficacy and Safety of Mini-dose Glucagon for Treatment of Non-severe Hypoglycemia in Adults With Type 1 Diabetes

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: G-Pen Mini™ (glucagon injection)
* Other: Glucose Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of presumed autoimmune T1D and receiving daily insulin Age: 18.0 to < 65.0 years Duration of T1D: ≥2.0 years Body mass index 20.0 to <35.0 kg/m2 and weight 110 to <250 lbs HbA1c <8.5% (point of care or local lab, within past month) Using continuous subcutaneous insulin infusion (CSII) therapy (i.e., insulin pump) for at least 3 months, with no plans to discontinue use during the study (and no use of active low glucose suspend feature within the last 4 weeks) Using continuous glucose monitor ≥6 days/week in the last 4 weeks, with no plans to discontinue continuous glucose monitor use during the study Continuous glucose monitor glucose level <70 mg/dl during daytime hours (e.g., 8am - 10pm) on at least 7 of the past 28 days (a modification can be made for participants with non-traditional waking hours) evaluated from downloaded CGM data Females must meet one of the following criteria: Of childbearing potential and not currently pregnant (negative pregnancy test) or lactating, and agrees to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study (from screening visit until study completion); or Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses) In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations Willing to adhere to the protocol requirements for the duration of the study Participant has a smart phone available and is able to use it daily Must be enrolled in the T1D Exchange clinic registry or willing to join the clinic registry Exclusion Criteria: More than 1 severe hypoglycemic episode in the past 12 months (as defined by an episode that required third party assistance for treatment) More than 1 episode of diabetic ketoacidosis in the past 12 months (as defined by an episode diagnosed as diabetic ketoacidosis that required treatment in an emergency department or hospitalization) Presence of cardiovascular, gastrointestinal, liver or kidney disease, or any medical condition which, in the judgment of the investigator, could potentiate or predispose to undesired effects or could interfere with the absorption, distribution, metabolism, or excretion of glucagon or ability to respond appropriately to mild to moderate hypoglycemia. Known presence of hereditary problems of glycogen storage disease, galactose and/or lactose intolerance Males with alcohol use in excess of 3 or more drinks per day, on average and females with alcohol use in excess of 2 or more drinks per day, on average Use of non-insulin anti-diabetic medications Use of daily systemic beta-blocker Use of beta-adrenergic agonists, theophylline (or other methylxanthines) Use of 1st generation anticholinergic drugs (such as Brompheniramine, Chlorpheniramine, Dimenhydrinate, Diphenhydramine, and Doxylamine) Use of systemic corticosteroids History of hypersensitivity to glucagon or any related product or excipient or severe hypersensitivity reactions (such as angioedema) to any drugs History of epilepsy or seizure disorder Uncontrolled hypertension, >160 mmHg systolic or >100 mmHg diastolic Currently a high endurance exerciser or plans to perform high endurance exercise during study (from screening visit until study completion) High endurance exerciser defined as a person who regularly competes in running, cycling, rowing, swimming or any other endurance-based activity for the purpose of competition (>2100 metabolic equivalent of task (MET) minutes per week [i.e. 7 METs x 60 minutes x 5 days a week, where 7 METs is equivalent to jogging]) Currently following a very low calorie or other weight-loss diet Participation in other studies involving administration of an investigational drug or device within 30 days or 5 half-lives, whichever is longer, before screening for the current study or planning to participate in another such study during participation in the current study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G-Pen Mini™ (glucagon injection)<br>Participants are to check blood glucose (BG) with study meter once their continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants will be instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). For every event, participant will check BG with meter 3 times and treat according to protocol instructions based on BG measurement. | Drug: G-Pen Mini™ (glucagon injection)<br>* 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon (150 µg of glucagon per syringe)<br>* Other names: mini-dose glucagon;|
| Active Comparator: Glucose Tabs<br>Participants are to check their blood glucose (BG) with study meter once their continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants will be instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). For every event, participant will check BG with meter 3 times and treat according to protocol instructions based on BG measurement. | Other: Glucose Tablets<br>* 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon (5 grams of fast-acting carbohydrates (D-Glucose) per tablet)<br>* Other names: over-the-counter oral glucose tablets; glucose tabs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Hypoglycemic Events ≥50 mg/dl 15 Minutes AND ≥ 70 mg/dl 30 Minutes After Initial Treatment |  | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous Glucose Monitor (CGM) Minimum Glucose, Event Level | Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event | 60 Minutes | 
| CGM Maximum Glucose, Event Level | Maximum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event | 60 Minutes | 
| CGM Mean Glucose, Event Level | Median (IQR) reported for mean glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event | 60 Minutes | 
| CGM Time in Range, Event Level | Percentage of time 70-180 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event | 60 Minutes | 
| CGM Time Below 70 mg/dL, Event Level | Percentage of time <70 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event | 60 Minutes | 
| CGM Minimum Glucose, Event Level | Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event | 120 Minutes | 
| CGM Maximum Glucose, Event Level | Maximum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event | 120 Minutes | 
| CGM Mean Glucose, Event Level | Median (IQR) reported for mean glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event | 120 Minutes | 
| CGM Time in Range, Event Level | Percentage of time 70-180 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event | 120 Minutes | 
| CGM Time Below 70 mg/dL | Percentage of time <70 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event | 120 Minutes | 
| CGM Mean Glucose | Median (IQR) reported for mean glucose from CGM data computed over entire 3 weeks of treatment period | 3 weeks | 
| CGM Time in Range | Percentage of time 70-180 mg/dL from CGM data computed over entire 3 weeks of treatment period | 3 weeks | 
| CGM Time Below 70 | Percentage of time <70 mg/dL from CGM data computed over entire 3 weeks of treatment period | 3 weeks | 
| CGM Coefficient of Variation | Coefficient of Variation from CGM data computed over entire 3 weeks of treatment period | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T1D, Type 1 diabetes, Mini-dose glucagon, adults, non-severe hypoglycemia