Efficacy and Safety of Dasiglucagon for Treatment of Post-bariatric Hypoglycemia in Roux-en-Y Gastric Bypass (RYGB) Operated Adults

Study Overview
=================
Brief Summary
-----------------
The objective of the trial is to assess the effect of single subcutaneous doses of dasiglucagon versus placebo on post-prandial plasma glucose nadir following a Mixed Meal Test in Roux-en-Y Gastric Bypass (RYGB) subjects

Official Title
-----------------
A Double-Blind, Placebo-Controlled, Cross-over Trial, Evaluating Efficacy and Safety of Dasiglucagon for Treatment of Post-bariatric Hypoglycemia in Roux-en-Y Gastric Bypass (RYGB) Operated Adults

Conditions
-----------------
Hypoglycemia, Glucose Metabolism Disorders

Intervention / Treatment
-----------------
* Drug: Dasiglucagon
* Drug: Dasiglucagon
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Previously undergone Roux-en-Y gastric bypass (RYGB) surgery at least 6 months prior to screening Previous diagnosis of post-bariatric hypoglycemia (PBH), requiring intake of oral carbohydrates. Body mass index (BMI) ≤ 40 kg/m2 Fasting plasma glucose between 72-106 mg/dL (4.0-6.0 mmol/l) Exclusion Criteria: History of hypersensitivity reactions to glucagon or dasiglucagon or any of the excipients History of insulinoma, pheochromocytoma, MEN 2A, MEN 2B, neurofibromatosis, or von Hippel-Lindau disease. Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m2 or end-stage renal disease at screening Hepatic disease, including serum alanine aminotransferase or aspartate aminotransferase ≥ 2.5 times the upper limit of normal (ULN) Active malignancy, except for basal or squamous cell skin cancers History of a cerebrovascular accident within 6 months prior to screening History of myocardial infarction, unstable angina, or revascularization within 6 months prior to screening. Congestive heart failure, New York Heart Association Class III or IV Concurrent administration of β-blocker therapy Clinically significant ECG abnormalities at screening

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>Dasiglucagon high dose, followed by placebo, followed by dasiglucagon low dose | Drug: Dasiglucagon<br>* dasiglucagon SC, low dose<br>Drug: Dasiglucagon<br>* dasiglucagon SC, high dose<br>Drug: Placebo<br>* placebo for dasiglucagon<br>|
| Experimental: Sequence 2<br>Dasiglucagn low dose, followed by dasiglucagon high dose, followed by placebo | Drug: Dasiglucagon<br>* dasiglucagon SC, low dose<br>Drug: Dasiglucagon<br>* dasiglucagon SC, high dose<br>Drug: Placebo<br>* placebo for dasiglucagon<br>|
| Experimental: Sequence 3<br>Placebo, followed by dasiglucagon low dose, followed by dasiglucagon high dose | Drug: Dasiglucagon<br>* dasiglucagon SC, low dose<br>Drug: Dasiglucagon<br>* dasiglucagon SC, high dose<br>Drug: Placebo<br>* placebo for dasiglucagon<br>|
| Experimental: Sequence 4<br>Dasiglucagon high dose, followed by dasiglucagon low dose, followed by placebo | Drug: Dasiglucagon<br>* dasiglucagon SC, low dose<br>Drug: Dasiglucagon<br>* dasiglucagon SC, high dose<br>Drug: Placebo<br>* placebo for dasiglucagon<br>|
| Experimental: Sequence 5<br>Placebo, followed by dasiglucagon high dose, followed by dasiglucagn low dose | Drug: Dasiglucagon<br>* dasiglucagon SC, low dose<br>Drug: Dasiglucagon<br>* dasiglucagon SC, high dose<br>Drug: Placebo<br>* placebo for dasiglucagon<br>|
| Experimental: Sequence 6<br>Dasiglucagon low dose, followed by placebo, followed by dasiglucagon high dose | Drug: Dasiglucagon<br>* dasiglucagon SC, low dose<br>Drug: Dasiglucagon<br>* dasiglucagon SC, high dose<br>Drug: Placebo<br>* placebo for dasiglucagon<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nadir plasma glucose concentration |  | From trial drug administration to 240 minutes after initiation of Mixed Meal Test | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent time spent in hypoglycemia | Defined as time with a plasma glucose value of 70 mg/dL (3.9 mmol/L) or less | From trial drug administration to 240 minutes after initiation of Mixed Meal Test | 
| Percent time spent in clinical significant hypoglycemia | Defined as time with a plasma glucose value of 54 mg/dL (3.0 mmol/L) or less | From trial drug administration to 240 minutes after initiation of Mixed Meal Test | 
| Percent time spent in target range | Defined as time with a plasma glucose value of 70-180 mg/dL (3.9-10.0 mmol/L) | From trial drug administration to 240 minutes after initiation of Mixed Meal Test | 
| Percent time spent in hyperglycemia | Defined as time with a plasma glucose value >180 mg/dL (>10 mmol/l) | From trial drug administration to 240 minutes after initiation of Mixed Meal Test |