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

NCT ID: NCT03984370

Last Updated: 2020-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-18
• Study Completion Date: 2020-02-26

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:

1. Subcutaneous (sc) placebo (saline) injection

2. Sc injection with 80 μg dasiglucagon

3. Sc injection with 200 μg dasiglucagon

Conditions

Hyperinsulinemic Hypoglycemia; Postprandial Hypoglycemia

Study Design

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

Study Groups

80 ug of sc dasiglucagon

80 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia.

Group Type: EXPERIMENTAL

ZP4207

Intervention Type: DRUG

Abdominal SC administration

200 ug of sc dasiglucagon

200 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia.

Group Type: EXPERIMENTAL

ZP4207

Intervention Type: DRUG

Abdominal SC administration

0.4 mL of sc saline (placebo)

0.4 mL fluid (saline/placebo) is injected abdominal subcutaneous postprandial prior to hypoglycemia.

Group Type: PLACEBO_COMPARATOR

Placebo (saline)

Intervention Type: OTHER

Abdominal SC administration

Interventions

ZP4207

Abdominal SC administration

Intervention Type: DRUG

Placebo (saline)

Abdominal SC administration

Intervention Type: OTHER

Other Intervention Names

Dasiglucagon

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.

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

Sponsors

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Filip Krag Knop

MD, professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Filip M. Knop, Prof., MD

Role: PRINCIPAL_INVESTIGATOR

Herlev-Gentofte Hospital, Center for Clinical Metabolic Research

Locations

Center for Clinical Metabolic Research, Herlev-Gentofte Hospital

Hellerup, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 35320361 (View on PubMed)

Other Identifiers

2019-001915-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CKN-DASI-RYGB

Identifier Type: -

Identifier Source: org_study_id