Trial Outcomes & Findings for Trial to Confirm the Clinical Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Subjects With T1DM (NCT NCT03688711)

NCT ID: NCT03688711

Last Updated: 2021-05-19

Results Overview

Plasma glucose recovery was defined as first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline during the hypoglycemic clamp procedure without administration of rescue intravenous (IV) glucose. Patients who received rescue IV glucose before 45 minutes and patients not recovering within 45 minutes after dosing were censored at 45 minutes.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 45 participants
• Primary outcome timeframe: 0-45 minutes after dosing
• Results posted on: 2021-05-19

Participant Flow

Participant milestones

Measure	Dasiglucagon 0.6 mg single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Overall Study STARTED	34	11
Overall Study COMPLETED	34	10
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Dasiglucagon 0.6 mg single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Trial to Confirm the Clinical Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Subjects With T1DM

Baseline characteristics by cohort

Measure	Dasiglucagon 0.6 mg n=34 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo n=10 Participants single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon	Total n=44 Participants Total of all reporting groups
Age, Continuous	42.4 years STANDARD_DEVIATION 13.49 • n=5 Participants	36.5 years STANDARD_DEVIATION 12.80 • n=7 Participants	41.0 years STANDARD_DEVIATION 13.42 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	1 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	9 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=5 Participants	7 Participants n=7 Participants	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	34 Participants n=5 Participants	7 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	34 Participants n=5 Participants	10 Participants n=7 Participants	44 Participants n=5 Participants
Body weight	84.49 kg STANDARD_DEVIATION 20.102 • n=5 Participants	83.69 kg STANDARD_DEVIATION 10.812 • n=7 Participants	84.30 kg STANDARD_DEVIATION 18.295 • n=5 Participants
Body mass index	28.41 kg per square metre STANDARD_DEVIATION 5.802 • n=5 Participants	27.92 kg per square metre STANDARD_DEVIATION 3.975 • n=7 Participants	28.30 kg per square metre STANDARD_DEVIATION 5.402 • n=5 Participants
Duration of diabetes	22.5 years STANDARD_DEVIATION 13.82 • n=5 Participants	21.2 years STANDARD_DEVIATION 13.42 • n=7 Participants	22.2 years STANDARD_DEVIATION 13.59 • n=5 Participants

PRIMARY outcome

Timeframe: 0-45 minutes after dosing

Population: The full analysis set of all randomized subjects who received at least one dose of trial drug (same as the safety analysis set)

Plasma glucose recovery was defined as first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline during the hypoglycemic clamp procedure without administration of rescue intravenous (IV) glucose. Patients who received rescue IV glucose before 45 minutes and patients not recovering within 45 minutes after dosing were censored at 45 minutes.

Outcome measures

Measure	Dasiglucagon 0.6 mg n=34 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo n=10 Participants single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Time to Plasma Glucose Recovery.	10.0 minutes Interval 8.0 to 12.0	35.0 minutes Interval 20.0 to The upper limit was not estimable due to insufficient number of participants reaching recovery

SECONDARY outcome

Timeframe: 0-30 minutes after dosing

Population: The full analysis set of all randomized subjects who received at least one dose of trial drug (same as the safety analysis set)

Plasma glucose recovery (patient has achieved increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L)) within 30 minutes, within 20 minutes, within 15 minutes, and within 10 minutes after trial drug injection without administration of rescue intravenous (IV) glucose.

Outcome measures

Measure	Dasiglucagon 0.6 mg n=34 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo n=10 Participants single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Plasma Glucose Recovery After Trial Drug Injection Glucose recovery within 30 minutes	33 Participants	5 Participants
Plasma Glucose Recovery After Trial Drug Injection Glucose recovery within 20 minutes	32 Participants	1 Participants
Plasma Glucose Recovery After Trial Drug Injection Glucose recovery within 15 minutes	30 Participants	0 Participants
Plasma Glucose Recovery After Trial Drug Injection Glucose recovery within 10 minutes	21 Participants	0 Participants

SECONDARY outcome

Timeframe: 0-30 minutes after dosing

Population: The full analysis set of all randomized subjects who received at least one dose of trial drug (same as the safety analysis set)

Plasma glucose changes from baseline at 30 minutes, at 20 minutes, at 15 minutes, and at 10 minutes after trial drug injection or at the time of rescue (patient level).

Outcome measures

Measure	Dasiglucagon 0.6 mg n=34 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo n=10 Participants single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Plasma Glucose Changes From Baseline At 30 minutes	85.29 mg/dL Standard Deviation 29.696	15.14 mg/dL Standard Deviation 9.328
Plasma Glucose Changes From Baseline At 20 minutes	52.95 mg/dL Standard Deviation 20.298	9.67 mg/dL Standard Deviation 8.846
Plasma Glucose Changes From Baseline At 15 minutes	41.62 mg/dL Standard Deviation 17.077	5.23 mg/dL Standard Deviation 6.686
Plasma Glucose Changes From Baseline At 10 minutes	24.54 mg/dL Standard Deviation 12.560	0.62 mg/dL Standard Deviation 6.100

SECONDARY outcome

Timeframe: 0-45 minutes after dosing

Population: The full analysis set of all randomized subjects who received at least one dose of trial drug (same as the safety analysis set)

Time to first plasma glucose concentration ≥70 mg/dL (3.9 mmol/L) without administration of rescue intravenous glucose

Outcome measures

Measure	Dasiglucagon 0.6 mg n=34 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo n=10 Participants single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Time to Target Plasma Glucose Concentration	9.0 minutes Interval 8.0 to 10.0	27.5 minutes Interval 12.0 to 40.0

SECONDARY outcome

Timeframe: 0-30 minutes after dosing

Population: The full analysis set of all randomized subjects who received at least one dose of trial drug (same as the safety analysis set)

Plasma glucose response as area under the effect curve (AUE) above baseline from time zero to 30 minutes, AUE0-30min.

Outcome measures

Measure	Dasiglucagon 0.6 mg n=34 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo n=10 Participants single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Pharmacodynamics - Area Under the Effect Curve	19.9 hr*mg/dL Standard Deviation 8.41	2.67 hr*mg/dL Standard Deviation 3.06

SECONDARY outcome

Timeframe: 0-90 minutes after dosing

Population: The full analysis set of all randomized subjects who received at least one dose of trial drug (same as the safety analysis set)

Area under the drug concentration curve (AUC) from time zero to 90 minutes, AUC0-90min

Outcome measures

Measure	Dasiglucagon 0.6 mg n=34 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Pharmacokinetics - Area Under the Plasma Concentration Curve	1480 hr*pmol/L Geometric Coefficient of Variation 34.6	—

SECONDARY outcome

Timeframe: 0-120 minutes after dosing

Population: The full analysis set of all randomized subjects who received at least one dose of trial drug (same as the safety analysis set)

Area under the drug concentration curve (AUC) from time zero to 120 minutes, AUC0-120min

Outcome measures

Measure	Dasiglucagon 0.6 mg n=34 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Pharmacokinetics - Area Under the Plasma Concentration Curve	1780 hr*pmol/L Geometric Coefficient of Variation 31.6	—

SECONDARY outcome

Timeframe: 0-120 minutes after dosing

Population: The full analysis set of all randomized subjects who received at least one dose of trial drug (same as the safety analysis set)

Maximum plasma dasiglucagon concentration (Cmax)

Outcome measures

Measure	Dasiglucagon 0.6 mg n=34 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Pharmacokinetics - Maximum Plasma Concentration	1350 pmol/L Geometric Coefficient of Variation 38.2	—

SECONDARY outcome

Timeframe: 0-120 minutes after dosing

Population: The full analysis set of all randomized subjects who received at least one dose of trial drug (same as the safety analysis set)

Time to maximum plasma dasiglucagon concentration (tmax)

Outcome measures

Measure	Dasiglucagon 0.6 mg n=34 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Pharmacokinetics - Time to Maximum Plasma Concentration	35 minutes Interval 15.0 to 60.0	—

SECONDARY outcome

Timeframe: 58 days

Population: The safety analysis set of all randomized subjects who received at least one dose of trial drug (same as the full analysis set)

Occurrence of antibodies against dasiglucagon. Presented as percentage of patients with antibodies.

Outcome measures

Measure	Dasiglucagon 0.6 mg n=34 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo n=10 Participants single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Immunogenicity - Occurrence of Anti-drug Antibodies	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 0-45 minutes after dosing

Population: The full analysis set of all randomized subjects who received at least one dose of trial drug (same as the safety analysis set)

Presented as number of patients with rescue infusions of IV glucose after trial drug administration. This was a safety outcome measure. IV = intravenous

Outcome measures

Measure	Dasiglucagon 0.6 mg n=34 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo n=10 Participants single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Rescue Infusions of IV Glucose After Trial Drug Administration	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 0-45 minutes after dosing

Population: Only the patients who received IV glucose administration are included.

Safety outcome measure: time to first rescue infusion of IV glucose after trial drug administration. IV = intravenous

Outcome measures

Measure	Dasiglucagon 0.6 mg n=1 Participants single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo n=1 Participants single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Time to First Rescue Infusion of IV Glucose After Trial Drug Administration	10 minutes	14 minutes

Adverse Events

Dasiglucagon 0.6 mg

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Dasiglucagon 0.6 mg n=34 participants at risk single fixed dose (subcutaneous injection) of dasiglucagon Dasiglucagon: Glucagon analogue	Placebo n=10 participants at risk single fixed dose (subcutaneous injection) of placebo Placebo: Placebo for dasiglucagon
Gastrointestinal disorders Nausea	61.8% 21/34 • Number of events 21 • 8 weeks	10.0% 1/10 • Number of events 1 • 8 weeks
Gastrointestinal disorders Vomiting	29.4% 10/34 • Number of events 11 • 8 weeks	0.00% 0/10 • 8 weeks
Gastrointestinal disorders Diarrhea	5.9% 2/34 • Number of events 2 • 8 weeks	0.00% 0/10 • 8 weeks
Gastrointestinal disorders Dyspepsia	0.00% 0/34 • 8 weeks	10.0% 1/10 • Number of events 1 • 8 weeks
Metabolism and nutrition disorders Hypoglycemia	17.6% 6/34 • Number of events 29 • 8 weeks	20.0% 2/10 • Number of events 3 • 8 weeks
Nervous system disorders Headache	11.8% 4/34 • Number of events 4 • 8 weeks	0.00% 0/10 • 8 weeks
Nervous system disorders Dizziness	2.9% 1/34 • Number of events 1 • 8 weeks	0.00% 0/10 • 8 weeks
General disorders Injection site pain	5.9% 2/34 • Number of events 2 • 8 weeks	0.00% 0/10 • 8 weeks
General disorders Infusion site extravasation	2.9% 1/34 • Number of events 1 • 8 weeks	0.00% 0/10 • 8 weeks
General disorders Injection site erythema	2.9% 1/34 • Number of events 1 • 8 weeks	0.00% 0/10 • 8 weeks
Infections and infestations Upper respiratory tract infection	0.00% 0/34 • 8 weeks	10.0% 1/10 • Number of events 1 • 8 weeks
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.9% 1/34 • Number of events 1 • 8 weeks	0.00% 0/10 • 8 weeks
Skin and subcutaneous tissue disorders Hyperhidrosis	2.9% 1/34 • Number of events 1 • 8 weeks	0.00% 0/10 • 8 weeks
Vascular disorders Phlebitis	2.9% 1/34 • Number of events 1 • 8 weeks	0.00% 0/10 • 8 weeks

Additional Information

Dr Kim Mark Knudsen

Zealand Pharma A/S

Phone: +4550603780

Email: KMKnudsen@zealandpharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place