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

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

Study Overview

• Status: Completed
• Conditions: Hyperinsulinemic Hypoglycemia; Postprandial Hypoglycemia
• Intervention / Treatment: Drug: ZP4207; Other: Placebo (saline)

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:

1. Subcutaneous (sc) placebo (saline) injection
2. Sc injection with 80 μg dasiglucagon
3. Sc injection with 200 μg dasiglucagon

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Center for Clinical Metabolic Research, Herlev-Gentofte Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 80 ug of sc dasiglucagon; 80 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia.	Drug: ZP4207; Abdominal SC administration; Other Names: Dasiglucagon
EXPERIMENTAL: 200 ug of sc dasiglucagon; 200 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia.	Drug: ZP4207; Abdominal SC administration; Other Names: Dasiglucagon
PLACEBO_COMPARATOR: 0.4 mL of sc saline (placebo); 0.4 mL fluid (saline/placebo) is injected abdominal subcutaneous postprandial prior to hypoglycemia.	Other: Placebo (saline); Abdominal SC administration

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

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Investigators: Principal Investigator: Filip M. Knop, Prof., MD, Herlev-Gentofte Hospital, Center for Clinical Metabolic Research

Publications and helpful links

General Publications

• Nielsen CK, Ohrstrom CC, Kielgast UL, Hansen DL, Hartmann B, Holst JJ, Lund A, Vilsboll T, Knop FK. Dasiglucagon Effectively Mitigates Postbariatric Postprandial Hypoglycemia: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial. Diabetes Care. 2022 Jun 2;45(6):1476-1481. doi: 10.2337/dc21-2252.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 18, 2019
• Primary Completion (ACTUAL): February 26, 2020
• Study Completion (ACTUAL): February 26, 2020

Study Registration Dates

• First Submitted: June 6, 2019
• First Submitted That Met QC Criteria: June 11, 2019
• First Posted (ACTUAL): June 13, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2020
• Last Update Submitted That Met QC Criteria: March 28, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Infant, Newborn, Diseases; Hyperinsulinism; Pancreatic Diseases; Hypoglycemia; Congenital Hyperinsulinism; Nesidioblastosis
• Other Study ID Numbers: CKN-DASI-RYGB; 2019-001915-22 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No