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

Postprandial Hypoglycemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03984370
• Other study ID #: CKN-DASI-RYGB
• Secondary ID: 2019-001915-22
• Status: Completed
• Phase: Phase 2
• Start date: September 18, 2019
• Est. completion date: February 26, 2020

Study information

• Verified date: March 2020
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: February 26, 2020
• Est. primary completion date: February 26, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Congenital Hyperinsulinism
• Hyperinsulinemic Hypoglycemia
• Hypoglycemia
• Postprandial Hypoglycemia

Intervention

Drug:
• ZP4207
Abdominal SC administration

Other:
• Placebo (saline)
Abdominal SC administration

Locations

Country	Name	City	State
Denmark	Center for Clinical Metabolic Research, Herlev-Gentofte Hospital	Hellerup

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Time in hypoglycaemia (plasma glucose concentration <3.9 mmol/l) from study drug administration until 240 minutes	Time in hypoglycaemia	Two hundred forty minutes
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	The Dumping Severity Score (DSS).	likert scale, zero (absent) to three (severe)	t=zero to t=Two hundred forty minutes
Secondary	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