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

Phase 2

Completed

• Conditions: Postprandial Hypoglycemia; Hyperinsulinemic Hypoglycemia
• Interventions: Other: Placebo (saline); Drug: ZP4207

• Registration Number: NCT03984370
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

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

Study Timeline

• Study First Submitted: 2019-06-06
• Study First Submitted QC: 2019-06-11
• Study First Posted: 2019-06-13
• Study Start: 2019-09-18
• Primary Completion: 2020-02-26
• Study Completion: 2020-02-26
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-28
• Last Update Posted: 2020-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
0.4 mL of sc saline (placebo)	Placebo (saline)	0.4 mL fluid (saline/placebo) is injected abdominal subcutaneous postprandial prior to hypoglycemia.
80 ug of sc dasiglucagon	ZP4207	80 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia.
200 ug of sc dasiglucagon	ZP4207	200 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia.

Primary Outcome Measures

Name	Time	Method
Nadir plasma glucose concentration within two hundred forty minutes after MMT	Two hundred forty minutes	Nadir plasma glucose concentration within two hundred forty minutes after MMT

Secondary Outcome Measures

Name	Time	Method
Frequency and severity of adverse events and serious adverse events recorded during the meal test	from t= minus thirty to t=Two hundred forty minutes	Frequency
Time in hypoglycaemia (plasma glucose concentration <3.9 mmol/l) from study drug administration until 240 minutes	Two hundred forty minutes	Time in hypoglycaemia
Time below fasting plasma glucose level from study drug administration until two hundred forty minutes	Two hundred forty minutes	Time below 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 from dasiglucagon administration to recovery (first plasma glucose value above the fasting plasma glucose level
Edinburgh Hypoglycaemia Symptom Scale (EHSS) responses of the Edinburgh Hypoglycaemia Symptom Scale (EHSS) and early dumping symptoms based on	t=zero to t=Two hundred forty minutes	likert scale one (absent) to seven (severe)
The Dumping Severity Score (DSS).	t=zero to t=Two hundred forty minutes	likert scale, zero (absent) to three (severe)
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.	Two hundred forty minutes	Area 1
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.	Two hundred forty minutes	Area 2

Trial Locations

Locations (1)

Center for Clinical Metabolic Research, Herlev-Gentofte Hospital; 🇩🇰 Hellerup, Denmark