Clinical Trial Results:
Ready-to-use dasiglucagon for the treatment of postprandial hypoglycaemia in Roux-en-Y gastric bypass operated patients
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Summary
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EudraCT number |
2020-005241-16 |
Trial protocol |
DK |
Global end of trial date |
12 Jun 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Sep 2023
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First version publication date |
27 Sep 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CKN-DASI120-RYGB
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03984370 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Center for Clinical Metabolic Research at Gentofte Hospital
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Sponsor organisation address |
Gentofte Hospitalsvej 7, hall 7, 3rd floor, Hellerup, Denmark, 2900
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Public contact |
Herlev-Gentofte Hospital, Center for Clinical Metabolic Research at Gentofte Hospital, +45 60117434, casper.kjaersgaard.nielsen@regionh.dk
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Scientific contact |
Herlev-Gentofte Hospital, Center for Clinical Metabolic Research at Gentofte Hospital, 60117434 60117434, casper.kjaersgaard.nielsen@regionh.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Aug 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Jun 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Jun 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary aim of the study is to compare the effects of self-administered 120 µg dasiglucagon versus placebo (during postprandial hypoglycaemia) on CGM-assessed time spent in hypoglycaemia in RYGB-operated individuals in an out-patient setting.
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Protection of trial subjects |
N/A
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Aug 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 24
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Worldwide total number of subjects |
24
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EEA total number of subjects |
24
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
24
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
• Interview of history of RYGB-surgery, PBH and neuroglycopenia • Review of inclusion and exclusion criteria • Blood pressure and pulse measurement • Weight and height measurement • ECG recording | |||||||||
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Pre-assignment
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Screening details |
• 14 days of blinded CGM recording verifying PBH at least three times a week | |||||||||
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Period 1
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Period 1 title |
Overall placebo and 120 ug dasiglucagon (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator | |||||||||
Blinding implementation details |
The outpatient treatment period comprised two consecutive unbroken treatment periods of either four weeks of self-administered placebo or dasiglucagon in random and double-blind order and with a one-week interposed washout period. Placebo and dasiglucagon were contained in indistinguishable cartridges. All participants and study personnel maintained blinding throughout the study.
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Placebo | |||||||||
Arm description |
Four weeks of self-administered placebo SC injections at the onset of hypoglycemia | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.03 ml of placebo
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Arm title
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120 ug dasiglucagon | |||||||||
Arm description |
Four weeks of self-administered 120 ug of dasiglucagon at the onset of hypoglycemia | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Dasiglucagon
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Investigational medicinal product code |
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Other name |
ZP4207
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Pharmaceutical forms |
Solution for injection in multidose container
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
120 ug of dasiglucagon (4 mg/ml) using a pen which was a multi-dose reusable pen injector for single-patient use with a replaceable cartridge-based system. The cartridge is pre-filled by the manufacturer (Zealand Pharma) and inserted by the user (participants).
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Baseline characteristics reporting groups
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Reporting group title |
Overall placebo and 120 ug dasiglucagon
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Reporting group description |
24 subjects at baseline | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Four weeks of self-administered placebo SC injections at the onset of hypoglycemia | ||
Reporting group title |
120 ug dasiglucagon
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Reporting group description |
Four weeks of self-administered 120 ug of dasiglucagon at the onset of hypoglycemia | ||
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End point title |
The percentage of time spent in hypoglycaemia (IG <3.9 mmol/l) assessed by CGM during the out-patient part of the study | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
four weeks of self-administered placebo vs four weeks of self-administered dasiglucagon
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Statistical analysis title |
mixed linear model | ||||||||||||
Statistical analysis description |
mixed linear model with treatments and periods as fixed factor and a random subject effect
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Comparison groups |
Placebo v 120 ug dasiglucagon
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Number of subjects included in analysis |
48
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.002 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
Percentage of time spent in level 2 hypoglycaemia (IG <3.0 mmol/l) as assessed by CGM during the outpatient part of the study. | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
four weeks of self-administered placebo vs four weeks of self-administered dasiglucagon
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Statistical analysis title |
mixed linear model | ||||||||||||
Statistical analysis description |
mixed linear model with treatments and periods as fixed factor and a random subject effect
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Comparison groups |
Placebo v 120 ug dasiglucagon
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Number of subjects included in analysis |
48
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.001 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
Frequency of hypoglycaemic events (IG <3.9 mmol/) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Four weeks of placebo treatment vs four weeks dasiglucagon treatment
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Statistical analysis title |
mixed linear model | ||||||||||||
Statistical analysis description |
mixed linear model with treatments and periods as fixed factor and a random subject effect
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Comparison groups |
Placebo v 120 ug dasiglucagon
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Number of subjects included in analysis |
48
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.16 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
Frequency of level 2 hypoglycaemic events (IG <3.0 mmol/l) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Four weeks of placebo treatment vs four weeks dasiglucagon treatment
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
from signed consent form to end of study (0-16 weeks)
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Adverse event reporting additional description |
Collected on a weekly basis during phone interviews
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
23.1
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: During the treatment periods, seven participants (29%) treated with dasiglucagon reported a total of 25 incidences of mild-to-moderate nausea compared with two participants (8%) who reported a total of two incidences in the placebo period. These events were primarily driven by three participants who reported 28 adverse events during dasiglucagon treatment, with nausea (20 counts) and dizziness (4 counts) being the most frequent. No adverse events lead to premature discontinuation from the trial |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
