Treatment of Post-bariatric Hypoglycaemia

NCT04836273 | Completed Phase 2 DMC

• 2 other identifiers: CKN-DASI120-RYGB2020-005241-16
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperinsulinemic Hypoglycemia; Postprandial Hypoglycemia

Outcome Measures

Primary Outcomes (1)

• 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.

  During the four weeks of placebo and dasiglucagon treatment.

Secondary Outcomes (24)

• Time (percent or minutes) spent in serious hypoglycaemia (IG <3.0 mmol/l)

  During the four weeks of placebo and dasiglucagon treatment.

• Frequency of hypoglycaemic events (IG <3.9 mmol/l and <3.0 mmol/l, respectively)

  During the four weeks of placebo and dasiglucagon treatment.

• Glycaemic time in range defined as: 1) hypoglycaemia (<3.9 mmol/l), 2) normoglycaemia (3.9-10.0 mmol/l), and 3) hyperglycaemia (>10.0 mmol/l)

  During the four weeks of placebo and dasiglucagon treatment.

• Frequency of hyperglycaemic events (IG >7.8 mmol/l and >10.0 mmol/l, respectively)

  During the four weeks of placebo and dasiglucagon treatment.

• Glycaemic variability assessed as coefficient of variance (CV)

  During the four weeks of placebo and dasiglucagon treatment.

Study Arms (2)

120 µg dasiglucagon

EXPERIMENTAL

Subcutaneous 120 µg dasiglucagon self-administration

Drug: Dasiglucagon; Device: HyoPen

Placebo

PLACEBO COMPARATOR

Subcutaneous placebo self-administration

Device: HyoPen; Drug: Placebo

Interventions

Dasiglucagon 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.

Also known as: ZP4207

120 µg dasiglucagon

HyoPen DEVICE

multi-dose reusable pen injector

Also known as: Zealand Pen

120 µg dasiglucagon; Placebo

Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Filip Krag Knop: lead
• Zealand Pharma: collaborator

Study Sites (1)

Center for Clinical Metabolic Research, Herlev-Gentofte Hospital

Hellerup, 2900, Denmark

Location

MeSH Terms

Conditions

Congenital Hyperinsulinism; Hypoglycemia

Interventions

dasiglucagon

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Filip K Knop, MD, PhD

  Center for Clinical Metabolic Research at Gentofte Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind (participants and investigator)
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Clinical Professor

Model Details: 4 weeks x 4 weeks with an interposed washout period of 1 week

Study Record Dates

• First Submitted: March 26, 2021
• First Posted: April 8, 2021
• Study Start: August 20, 2021
• Primary Completion: May 15, 2022
• Study Completion: December 15, 2022
• Last Updated: February 2, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)