Treatment of Post-bariatric Hypoglycaemia

Postprandial Hypoglycemia Clinical Trial

— SHERRY  

Official title:

Ready-to-use Dasiglucagon for the Treatment of Postprandial Hypoglycaemia in Roux-en-Y Gastric Bypass Operated Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04836273
• Other study ID #: CKN-DASI120-RYGB
• Secondary ID: 2020-005241-16
• Status: Completed
• Phase: Phase 2
• Start date: August 20, 2021
• Est. completion date: December 15, 2022

Study information

• Verified date: February 2023
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Study design:

Before inclusion in the study, the participants will complete a screening visit and a blinded 14-day continuous glucose monitoring (CGM) run-in period to ascertain a regular occurrence of postprandial hypoglycaemia (IG <3.9 mmol/l, ≥3 times/week). After enrolment in the study, the participants will wear a CGM for the entirety of the study period (apart from the four weeks before the follow-up visit). Prior to the first mixed meal test (MMT) during the in-patient part, the subjects will be randomised into one of four double-blinded treatment sequences consisting of an in-patient part (two MMTs) follow by a nine weeks out-patient part (two times four weeks per out-patient part with an interposed washout period of one week) and ended with a follow-up visit four weeks after out-patient part completion.

During the in-patient part, the participants will undergo two separate MMTs, with a minimum of 7 days in-between, accompanied by one of the following double-blind, randomised, placebo-controlled crossover interventions:

1. Subcutaneous placebo self-administration

2. Subcutaneous 120 µg dasiglucagon self-administration

The out-patient part is divided into two double-blinded, randomised, placebo-controlled crossover out-patient parts with of the following interventions:

1. Subcutaneous placebo self-administration

2. Subcutaneous 120 µg dasiglucagon self-administration

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 15, 2022
• Est. primary completion date: May 15, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Congenital Hyperinsulinism
• Hyperinsulinemic Hypoglycemia
• Hypoglycemia
• Nesidioblastosis
• Postprandial Hypoglycemia

Intervention

Drug:
• Dasiglucagon
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.

Device:
• HyoPen
multi-dose reusable pen injector

Drug:
• Placebo
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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Filip Krag Knop	Zealand Pharma

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time (percent or minutes) spent in serious hypoglycaemia (IG <3.0 mmol/l)		During the four weeks of placebo and dasiglucagon treatment.
Secondary	Frequency of hypoglycaemic events (IG <3.9 mmol/l and <3.0 mmol/l, respectively)		During the four weeks of placebo and dasiglucagon treatment.
Secondary	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.
Secondary	Frequency of hyperglycaemic events (IG >7.8 mmol/l and >10.0 mmol/l, respectively)		During the four weeks of placebo and dasiglucagon treatment.
Secondary	Glycaemic variability assessed as coefficient of variance (CV)		During the four weeks of placebo and dasiglucagon treatment.
Secondary	Glycaemic variability assessed as standard deviation (SD)		During the four weeks of placebo and dasiglucagon treatment.
Secondary	Recovery of BG 15 minutes after trial drug administration (as measured by finger prick (BG >3.9 mmol/l))		During the four weeks of placebo and dasiglucagon treatment.
Secondary	Change in QoL as assessed by the World Health Organization's quality of life assessment (WHOQOL-BREF)	likert scale, zero (very poor) to five (very good)	During the four weeks of placebo and dasiglucagon treatment.
Secondary	Change in hypoglycaemic symptoms will be evaluated by Edinburgh Hypoglycaemia Symptom Scale (EHSS)	likert scale, zero (not a all) to seven (a lot)	During the four weeks of placebo and dasiglucagon treatment.
Secondary	Change in fear of hypoglycaemia as assessed by Hypoglycaemia Fear Scale (HFS-II)	likert scale, zero (never) to four (always)	During the four weeks of placebo and dasiglucagon treatment.
Secondary	Change in administration frequency (as measured by percentage)		During the four weeks of placebo and dasiglucagon treatment.
Secondary	Nadir plasma glucose as assessed both as 1) absolute lowest value, and 2) a mean of three consecutive glucose measurements during the 240-minute MMT	Nadir plasma glucose after the postprandial peak during the MMT in the in-patient part	Two hundred forty minutes of mixed meal test
Secondary	Recovery of BG 15 minutes after administration (as measured by finger prick (BG >3.9 mmol/l))	After the postprandial peak during the MMT in the in-patient part	Two hundred forty minutes of mixed meal test
Secondary	Time spent in level 1 and level 2 hypoglycaemia (<3.9 and <3.0 mmol/l, respectively) from study drug administration until 240 minutes	After the postprandial peak during the MMT in the in-patient part	Two hundred forty minutes of mixed meal test
Secondary	Glycaemic rescue intervention due to critically low plasma glucose concentration (<1.8 mmol/l)	During the MMT in the in-patient part	Two hundred forty minutes of mixed meal test
Secondary	Time spent in hyperglycaemia (>7.8 mmol/l) from study drug administration until 240 minutes	During the MMT in the in-patient part	Two hundred forty minutes of mixed meal test
Secondary	Peak plasma glucose concentration after study drug administration	During the MMT in the in-patient part	Two hundred forty minutes of mixed meal test
Secondary	Counter-regulatory hormonal response	Measured as area under the curve (AUC) and / or incremental (iAUC) as appropriate, peak values and values at nadir plasma glucose concentration during the MMT in the in-patient part. glucagon-like peptide 1 (GLP-1), glucagon-like peptide 2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP)	Two hundred forty minutes of mixed meal test
Secondary	Changes in blood pressure	During the MMT in the in-patient part	Two hundred forty minutes of mixed meal test
Secondary	Changes in heart rate	During the MMT in the in-patient part	Two hundred forty minutes of mixed meal test
Secondary	Frequency and severity of adverse events (AE)s and serious adverse events (SAE)s from signed consent form to end of study (visit 4 / follow-up visit)	Safety endpoint	Through study completion which is an average of 16 weeks
Secondary	Frequency and severity of adverse events (AE)s and serious adverse events (SAE)s during the in-patient part MMTs	Safety endpoint	During the in-patient part (MMTs) 0-240 minutes / Two hundred forty minutes of mixed meal test
Secondary	Percentage (%) of participants with treatment-induced or treatment-boosted anti-dasiglucagon antibodies who did not have anti-dasiglucagon antibodies at baseline	Safety endpoint	Through study completion which is an average of 16 weeks
Secondary	Device failures/ malfunctions occurring during the trial.	Device endpoint	Through study completion which is an average of 16 weeks