Treatment of Post-bariatric Hypoglycaemia

NCT ID: NCT04836273

Last Updated: 2023-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-20
• Study Completion Date: 2022-12-15

Brief Summary

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.

Detailed Description

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

Conditions

Hyperinsulinemic Hypoglycemia; Postprandial Hypoglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

120 µg dasiglucagon

Subcutaneous 120 µg dasiglucagon self-administration

Group Type: EXPERIMENTAL

Dasiglucagon

Intervention Type: DRUG

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.

HyoPen

Intervention Type: DEVICE

multi-dose reusable pen injector

Placebo

Subcutaneous placebo self-administration

Group Type: PLACEBO_COMPARATOR

HyoPen

Intervention Type: DEVICE

multi-dose reusable pen injector

Placebo

Intervention Type: DRUG

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.

Interventions

Dasiglucagon

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.

Intervention Type: DRUG

HyoPen

multi-dose reusable pen injector

Intervention Type: DEVICE

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

ZP4207; Zealand Pen

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Zealand Pharma

INDUSTRY

Sponsor Role: collaborator

Filip Krag Knop

OTHER

Sponsor Role: lead

Responsible Party

Filip Krag Knop

Principal Investigator, Clinical Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Filip K Knop, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Center for Clinical Metabolic Research at Gentofte Hospital

Locations

Center for Clinical Metabolic Research, Herlev-Gentofte Hospital

Hellerup, , Denmark

Countries

Denmark

Other Identifiers

2020-005241-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CKN-DASI120-RYGB

Identifier Type: -

Identifier Source: org_study_id