Treatment of Post-bariatric Hypoglycaemia

Filip Krag Knop24 enrolled

Overview

This is an investigator-initiated, proof-of-concept, randomised, double-blind, placebo-controlled, single-centre phase II study aiming to evaluate the efficacy, safety and tolerability of self-administered subcutaneous 120 µg dasiglucagon with an investigational trial device (i.e. a multi-dose reusable pen) for the treatment of postprandial hypoglycaemia after Roux-en-Y gastric bypass (RYGB) surgery. The study is divided into an in-patient and out-patient part. The primary aim of the study is to compare the effects of self-administered 120 µg dasiglucagon versus placebo on continuous glucose monitoring (CGM)-assessed time spent in hypoglycaemia in RYGB-operated individuals in an out-patient setting.

Study design: Before inclusion in the study, the participants will complete a screening visit and a blinded 14-day continuous glucose monitoring (CGM) run-in period to ascertain a regular occurrence of postprandial hypoglycaemia (IG \<3.9 mmol/l, ≥3 times/week). After enrolment in the study, the participants will wear a CGM for the entirety of the study period (apart from the four weeks before the follow-up visit). Prior to the first mixed meal test (MMT) during the in-patient part, the subjects will be randomised into one of four double-blinded treatment sequences consisting of an in-patient part (two MMTs) follow by a nine weeks out-patient part (two times four weeks per out-patient part with an interposed washout period of one week) and ended with a follow-up visit four weeks after out-patient part completion. During the in-patient part, the participants will undergo two separate MMTs, with a minimum of 7 days in-between, accompanied by one of the following double-blind, randomised, placebo-controlled crossover interventions: 1. Subcutaneous placebo self-administration 2. Subcutaneous 120 µg dasiglucagon self-administration The out-patient part is divided into two double-blinded, randomised, placebo-controlled crossover out-patient parts with of the following interventions: 1. Subcutaneous placebo self-administration 2. Subcutaneous 120 µg dasiglucagon self-administration

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Interventions

DasiglucagonDRUG

Abdominal s.c. self-administration 120 µg of dasiglucagon when blood glucose levels are below 3.9 mmol/L or interstitial glucose levels below 3.5 mmol/L. The frequency of the intervention is approximately once a day.

HyoPenDEVICE

multi-dose reusable pen injector

PlaceboDRUG

Abdominal s.c. self-administration with placebo when blood glucose levels are below 3.9 mmol/L or interstitial glucose levels below 3.5 mmol/L. The frequency of the intervention is approximately once a day.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Documented postprandial hypoglycaemia (IG \<3.9 mmol/l, ≥3 times/week) assessed by 14-days of blinded CGM recording * 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 * Normal electrocardiogram (ECG) * Negative urine human chorionic gonadotropin (hCG) (for fertile women) Exclusion Criteria: * Treatment with medication(s) affecting insulin secretion, glucose metabolism or any antidiabetic drugs * Treatment with antipsychotics * Current participation in another clinical trial with administration of investigational drug * Previous exposure to dasiglucagon (also known as ZP4207) within the last 30 days prior screening * History of liver disease that is expected to interfere with the anti-hypoglycaemic action of glucagon (e.g. liver failure or cirrhosis) * Pregnancy * Breastfeeding * Major surgery within 30 days before screening * Alcohol abuse (per investigator assessment) * 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 * History of pheochromocytoma or insulinoma * History of hypersensitivity or allergic reaction to dasiglucagon or any of the excipients * Known or suspected allergies to glucagon or related products

Outcomes

Primary Outcomes

Time spent in hypoglycaemia (IG < 3.9 mmol)

The primary endpoint is the percentage of time in hypoglycaemia (IG \<3.9 mmol/l) assessed by CGM during the out-patient part.