Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass

Study Overview
=================
Brief Summary
-----------------
The aim of this study is investigating the effect of a novel glucagon analogue administration in gastric bypass operated individuals, who are reactive hypoglycemic.

Detailed Description
-----------------
The Roux-En-Y gastric bypass (RYGB) has major health-promoting effects - reversing type-2-diabetes, improving dyslipidemia and inducing robust weight loss. However, several RYGB-individuals, post surgery, suffers from dumping syndrome and postprandial hyperinsulinemic hypoglycemia (PHH) due to the anatomical rearrangement of the gastro-intestinal system. Dasiglugaon (also known as (ZP4207) has shown great pharmacokinetic- and dynamic effects, compared to other glucagon analogues on the market, when administrated to hypoglycemic type-1-diabetics. Therefore we aim to examine the effects of two different doses of dasiglucagon on the postprandial nadir plasma glucose concentration in RYGB-operated individuals suffering from PHH by use of a mixed meal test (MMT). The study is designed as a double-blinded, randomised, 3-period, 3-treatment, crossover study comprising 3 separate treatment days in which participants will undergo an MMT along with one of the following double-blinded interventions: Subcutaneous (sc) placebo (saline) injection Sc injection with 80 μg dasiglucagon Sc injection with 200 μg dasiglucagon

Official Title
-----------------
Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass

Conditions
-----------------
Hyperinsulinemic Hypoglycemia, Postprandial Hypoglycemia

Intervention / Treatment
-----------------
* Drug: ZP4207
* Other: Placebo (saline)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented postprandial hypoglycaemia (<3.9 mmol/l) by 6-day CGM or during a MMT Documented plasma glucose concentration excursions >5.0 mmol/l by 6-day CGM or a MMT Haemoglobin levels for women >7.3 mmol/l and for men >8.3 mmol/l Ferritin >10 μg/l Cobalamin >150 pmol/l Fasting plasma glucose concentration within the range of 4.0-6.0 mmol/l CKN-DASI-RYGB protocol version 1.0 6 Normal electrocardiogram (ECG) Negative urine human chorionic gonadotropin (hCG) (for fertile women) Exclusion Criteria: Treatment with medication(s) affecting insulin secretion or any antidiabetic drugs Treatment with antipsychotics Current participation in another clinical trial with administration of investigational drug. Previous exposure to dasiglucagon (otherwise known as ZP4207) History of liver disease that is expected to interfere with the anti-hypoglycaemic action of glucagon (e.g. liver failure or cirrhosis). Pregnancy Breastfeeding Any factors that, in the opinion of the site principal investigator or clinical protocol chair, would interfere with the safe completion of the study, including medical conditions that may require hospitalization during the trial or allergy to the ingredients in the study drug.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-blinded, randomised, 3-period, 3-treatment, crossover study comprising 3 separate treatment days
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 80 ug of sc dasiglucagon<br>80 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia. | Drug: ZP4207<br>* Abdominal SC administration<br>* Other names: Dasiglucagon;|
| Experimental: 200 ug of sc dasiglucagon<br>200 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia. | Drug: ZP4207<br>* Abdominal SC administration<br>* Other names: Dasiglucagon;|
| Placebo Comparator: 0.4 mL of sc saline (placebo)<br>0.4 mL fluid (saline/placebo) is injected abdominal subcutaneous postprandial prior to hypoglycemia. | Other: Placebo (saline)<br>* Abdominal SC administration<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nadir plasma glucose concentration within two hundred forty minutes after MMT | Nadir plasma glucose concentration within two hundred forty minutes after MMT | Two hundred forty minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from dasiglucagon administration to recovery (first plasma glucose value above the fasting plasma glucose level | Time from dasiglucagon administration to recovery (first plasma glucose value above the fasting plasma glucose level | Two hundred forty minutes | 
| Time in hypoglycaemia (plasma glucose concentration <3.9 mmol/l) from study drug administration until 240 minutes | Time in hypoglycaemia | Two hundred forty minutes | 
| Time below fasting plasma glucose level from study drug administration until two hundred forty minutes | Time below fasting plasma glucose level | Two hundred forty minutes | 
| Area 1: the area above the glucose curve and below the fasting level from the time of study drug administration until glucose values reach the fasting level. | Area 1 | Two hundred forty minutes | 
| Area 2: the area below the glucose curve and above the fasting level from the time glucose values reach the fasting level until 240 minutes. | Area 2 | Two hundred forty minutes | 
| Edinburgh Hypoglycaemia Symptom Scale (EHSS) responses of the Edinburgh Hypoglycaemia Symptom Scale (EHSS) and early dumping symptoms based on | likert scale one (absent) to seven (severe) | t=zero to t=Two hundred forty minutes | 
| The Dumping Severity Score (DSS). | likert scale, zero (absent) to three (severe) | t=zero to t=Two hundred forty minutes | 
| Frequency and severity of adverse events and serious adverse events recorded during the meal test | Frequency | from t= minus thirty to t=Two hundred forty minutes |