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Treatment of Post-bariatric Hypoglycaemia (SHERRY)

Primary Purpose

Hyperinsulinemic Hypoglycemia, Postprandial Hypoglycemia

Status

Completed

Phase

Phase 2

Locations

Denmark

Study Type

Interventional

Intervention

Dasiglucagon

HyoPen

Placebo

About this trial

This is an interventional treatment trial for Hyperinsulinemic Hypoglycemia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Center for Clinical Metabolic Research, Herlev-Gentofte Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

120 µg dasiglucagon

Placebo

Arm Description

Subcutaneous 120 µg dasiglucagon self-administration

Subcutaneous placebo self-administration

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Time (percent or minutes) spent in serious hypoglycaemia (IG <3.0 mmol/l)

Frequency of hypoglycaemic events (IG <3.9 mmol/l and <3.0 mmol/l, respectively)

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)

Frequency of hyperglycaemic events (IG >7.8 mmol/l and >10.0 mmol/l, respectively)

Glycaemic variability assessed as coefficient of variance (CV)

Glycaemic variability assessed as standard deviation (SD)

Recovery of BG 15 minutes after trial drug administration (as measured by finger prick (BG >3.9 mmol/l))

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)

Change in hypoglycaemic symptoms will be evaluated by Edinburgh Hypoglycaemia Symptom Scale (EHSS)

likert scale, zero (not a all) to seven (a lot)

Change in fear of hypoglycaemia as assessed by Hypoglycaemia Fear Scale (HFS-II)

likert scale, zero (never) to four (always)

Change in administration frequency (as measured by percentage)

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

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

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

Glycaemic rescue intervention due to critically low plasma glucose concentration (<1.8 mmol/l)

During the MMT in the in-patient part

Time spent in hyperglycaemia (>7.8 mmol/l) from study drug administration until 240 minutes

During the MMT in the in-patient part

Peak plasma glucose concentration after study drug administration

During the MMT in the in-patient part

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)

Changes in blood pressure

During the MMT in the in-patient part

Changes in heart rate

During the MMT in the in-patient part

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

Frequency and severity of adverse events (AE)s and serious adverse events (SAE)s during the in-patient part MMTs

Safety endpoint

Percentage (%) of participants with treatment-induced or treatment-boosted anti-dasiglucagon antibodies who did not have anti-dasiglucagon antibodies at baseline

Safety endpoint

Device failures/ malfunctions occurring during the trial.

Device endpoint

Full Information

NCT ID

NCT04836273

First Posted

March 26, 2021

Last Updated

February 1, 2023

Sponsor

Filip Krag Knop

Collaborators

Zealand Pharma

1. Study Identification

Unique Protocol Identification Number

NCT04836273

Brief Title

Treatment of Post-bariatric Hypoglycaemia

Acronym

SHERRY

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

August 20, 2021 (Actual)

Primary Completion Date

May 15, 2022 (Actual)

Study Completion Date

December 15, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Filip Krag Knop

Collaborators

Zealand Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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: Subcutaneous placebo self-administration 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: Subcutaneous placebo self-administration Subcutaneous 120 µg dasiglucagon self-administration

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hyperinsulinemic Hypoglycemia, Postprandial Hypoglycemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Model Description

4 weeks x 4 weeks with an interposed washout period of 1 week

Masking

ParticipantInvestigator

Masking Description

Double-blind (participants and investigator)

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

120 µg dasiglucagon

Arm Type

Experimental

Arm Description

Subcutaneous 120 µg dasiglucagon self-administration

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Subcutaneous placebo self-administration

Intervention Type

Drug

Intervention Name(s)

Dasiglucagon

Other Intervention Name(s)

ZP4207

Intervention Description

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.

Intervention Type

Device

Intervention Name(s)

HyoPen

Other Intervention Name(s)

Zealand Pen

Intervention Description

multi-dose reusable pen injector

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Time spent in hypoglycaemia (IG < 3.9 mmol)

Description

The primary endpoint is the percentage of time in hypoglycaemia (IG <3.9 mmol/l) assessed by CGM during the out-patient part.

Time Frame