Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass
Primary Purpose
Hyperinsulinemic Hypoglycemia, Postprandial Hypoglycemia
Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
ZP4207
Placebo (saline)
Sponsored by
About this trial
This is an interventional treatment trial for Hyperinsulinemic Hypoglycemia
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.
Sites / Locations
- Center for Clinical Metabolic Research, Herlev-Gentofte Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
80 ug of sc dasiglucagon
200 ug of sc dasiglucagon
0.4 mL of sc saline (placebo)
Arm Description
80 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia.
200 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia.
0.4 mL fluid (saline/placebo) is injected abdominal subcutaneous postprandial prior to hypoglycemia.
Outcomes
Primary Outcome Measures
Nadir plasma glucose concentration within two hundred forty minutes after MMT
Nadir plasma glucose concentration within two hundred forty minutes after MMT
Secondary Outcome Measures
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
Time in hypoglycaemia (plasma glucose concentration <3.9 mmol/l) from study drug administration until 240 minutes
Time in hypoglycaemia
Time below fasting plasma glucose level from study drug administration until two hundred forty minutes
Time below fasting plasma glucose level
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
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
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)
The Dumping Severity Score (DSS).
likert scale, zero (absent) to three (severe)
Frequency and severity of adverse events and serious adverse events recorded during the meal test
Frequency
Full Information
NCT ID
NCT03984370
First Posted
June 6, 2019
Last Updated
March 28, 2020
Sponsor
University Hospital, Gentofte, Copenhagen
1. Study Identification
Unique Protocol Identification Number
NCT03984370
Brief Title
Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass
Official Title
Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
September 18, 2019 (Actual)
Primary Completion Date
February 26, 2020 (Actual)
Study Completion Date
February 26, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Gentofte, Copenhagen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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:
Subcutaneous (sc) placebo (saline) injection
Sc injection with 80 μg dasiglucagon
Sc injection with 200 μg dasiglucagon
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
Double-blinded, randomised, 3-period, 3-treatment, crossover study comprising 3 separate treatment days
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
80 ug of sc dasiglucagon
Arm Type
Experimental
Arm Description
80 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia.
Arm Title
200 ug of sc dasiglucagon
Arm Type
Experimental
Arm Description
200 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia.
Arm Title
0.4 mL of sc saline (placebo)
Arm Type
Placebo Comparator
Arm Description
0.4 mL fluid (saline/placebo) is injected abdominal subcutaneous postprandial prior to hypoglycemia.
Intervention Type
Drug
Intervention Name(s)
ZP4207
Other Intervention Name(s)
Dasiglucagon
Intervention Description
Abdominal SC administration
Intervention Type
Other
Intervention Name(s)
Placebo (saline)
Intervention Description
Abdominal SC administration
Primary Outcome Measure Information:
Title
Nadir plasma glucose concentration within two hundred forty minutes after MMT
Description
Nadir plasma glucose concentration within two hundred forty minutes after MMT
Time Frame
Two hundred forty minutes
Secondary Outcome Measure Information:
Title
Time from dasiglucagon administration to recovery (first plasma glucose value above the fasting plasma glucose level
Description
Time from dasiglucagon administration to recovery (first plasma glucose value above the fasting plasma glucose level
Time Frame
Two hundred forty minutes
Title
Time in hypoglycaemia (plasma glucose concentration <3.9 mmol/l) from study drug administration until 240 minutes
Description
Time in hypoglycaemia
Time Frame
Two hundred forty minutes
Title
Time below fasting plasma glucose level from study drug administration until two hundred forty minutes
Description
Time below fasting plasma glucose level
Time Frame
Two hundred forty minutes
Title
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.
Description
Area 1
Time Frame
Two hundred forty minutes
Title
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.
Description
Area 2
Time Frame
Two hundred forty minutes
Title
Edinburgh Hypoglycaemia Symptom Scale (EHSS) responses of the Edinburgh Hypoglycaemia Symptom Scale (EHSS) and early dumping symptoms based on
Description
likert scale one (absent) to seven (severe)
Time Frame
t=zero to t=Two hundred forty minutes
Title
The Dumping Severity Score (DSS).
Description
likert scale, zero (absent) to three (severe)
Time Frame
t=zero to t=Two hundred forty minutes
Title
Frequency and severity of adverse events and serious adverse events recorded during the meal test
Description
Frequency
Time Frame
from t= minus thirty to t=Two hundred forty minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Filip M. Knop, Prof., MD
Organizational Affiliation
Herlev-Gentofte Hospital, Center for Clinical Metabolic Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Clinical Metabolic Research, Herlev-Gentofte Hospital
City
Hellerup
ZIP/Postal Code
2900
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35320361
Citation
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.
Results Reference
derived
Learn more about this trial
Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass
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