Mini-Dose Glucagon to Treat Non-Severe Hypoglycemia

Phase 2

Completed

• Conditions: Diabetes Mellitus, Type 1
• Interventions: Drug: G-Pen Mini™ (glucagon injection); Other: Glucose Tablets

• Registration Number: NCT02411578
• Lead Sponsor: Jaeb Center for Health Research

Brief Summary

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

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.

1. 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.

2. 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.

3. 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.

Study Timeline

• Study First Submitted: 2015-03-27
• Study First Submitted QC: 2015-04-03
• Study First Posted: 2015-04-08
• Study Start: 2015-09
• Primary Completion: 2016-04
• Study Completion: 2016-05
• Results First Submitted: 2017-08-03
• Results First Submitted QC: 2017-09-20
• Results First Posted: 2017-10-23
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-28
• Last Update Posted: 2020-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

1. Clinical diagnosis of presumed autoimmune T1D and receiving daily insulin

2. Age: 18.0 to < 65.0 years

3. Duration of T1D: ≥2.0 years

4. Body mass index 20.0 to <35.0 kg/m2 and weight 110 to <250 lbs

5. HbA1c <8.5% (point of care or local lab, within past month)

6. 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)

7. Using continuous glucose monitor ≥6 days/week in the last 4 weeks, with no plans to discontinue continuous glucose monitor use during the study

8. 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

9. 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)

10. 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

11. Willing to adhere to the protocol requirements for the duration of the study

12. Participant has a smart phone available and is able to use it daily

13. Must be enrolled in the T1D Exchange clinic registry or willing to join the clinic registry

Exclusion Criteria

1. More than 1 severe hypoglycemic episode in the past 12 months (as defined by an episode that required third party assistance for treatment)

2. 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)

3. 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.

4. Known presence of hereditary problems of glycogen storage disease, galactose and/or lactose intolerance

5. 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

6. Use of non-insulin anti-diabetic medications

7. Use of daily systemic beta-blocker

8. Use of beta-adrenergic agonists, theophylline (or other methylxanthines)

9. Use of 1st generation anticholinergic drugs (such as Brompheniramine, Chlorpheniramine, Dimenhydrinate, Diphenhydramine, and Doxylamine)

10. Use of systemic corticosteroids

11. History of hypersensitivity to glucagon or any related product or excipient or severe hypersensitivity reactions (such as angioedema) to any drugs

12. History of epilepsy or seizure disorder

13. Uncontrolled hypertension, >160 mmHg systolic or >100 mmHg diastolic

14. 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])

15. Currently following a very low calorie or other weight-loss diet

16. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
G-Pen Mini™ (glucagon injection)	G-Pen Mini™ (glucagon injection)	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.
Glucose Tabs	Glucose Tablets	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.

Primary Outcome Measures

Name	Time	Method
Number of Hypoglycemic Events ≥50 mg/dl 15 Minutes AND ≥ 70 mg/dl 30 Minutes After Initial Treatment	30 minutes

Secondary Outcome Measures

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

Trial Locations

Locations (5)

Yale University of Medicine; 🇺🇸 New Haven, Connecticut, United States

University of Colorado/Barbara Davis Center for Diabetes; 🇺🇸 Aurora, Colorado, United States

Joslin Diabetes Center; 🇺🇸 Boston, Massachusetts, United States

SUNY Upstate Medical University; 🇺🇸 Syracuse, New York, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States