A Trial to Confirm the Efficacy and Safety of Dasiglucago... | NCT03378635

Label	Type	Description	Intervention Names
Dasiglucagon	Experimental	Single fixed dose (s.c.injection) of dasiglucagon	Drug: Dasiglucagon
Placebo	Placebo Comparator	Single fixed dose (s.c.injection) of placebo	Drug: Placebo
GlucaGen®	Active Comparator	Single fixed dose (s.c.injection) of GlucaGen®	Drug: GlucaGen

Name	Type	Description	Arm Group Labels	Other Names
Dasiglucagon	Drug	Glucagon analog	Dasiglucagon	ZP4207

Measure	Description	Time Frame
Time to Plasma Glucose Recovery	Plasma glucose recovery is defined as first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline without administration of rescue intravenous glucose. The outcome measure used a Kaplan-Meier estimate with 95% confidence interval. Treatment groups without censoring utilized a distribution free method to compute the confidence interval for median time.	0-45 minutes after dosing

Measure	Description	Time Frame
Plasma Glucose Recovery	Plasma glucose recovery within 30 minutes, within 20 minutes, within 15 minutes, and within 10 minutes after study drug injection without administration of rescue IV glucose. Plasma glucose recovery was defined as the first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline without administration of rescue intravenous glucose.	0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection

Name	Affiliation	Role
Christina Sylvest, MSc Pharm	Zealand Pharma	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
ProSciento		Chula Vista	California	91911	United States
Clinical Research Center, Medizinische Universität Graz

PubMed Identifier	Type	Citation	Retractions
35239971	Derived	Pieber TR, Aronson R, Hovelmann U, Willard J, Plum-Morschel L, Knudsen KM, Bandak B, Tehranchi R. Dasiglucagon-A Next-Generation Glucagon Analog for Rapid and Effective Treatment of Severe Hypoglycemia: Results of Phase 3 Randomized Double-Blind Clinical Trial. Diabetes Care. 2021 Jun 1;44(6):1361-1367. doi: 10.2337/dc20-2995.

ID	Title	Description
FG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
FG001	Placebo	Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 8, 2019	Mar 25, 2021

ID	Title	Description
BG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
BG001	Placebo	Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon
BG002	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00082 BG00143 BG00243 BG003168

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Time to Plasma Glucose Recovery

Plasma glucose recovery is defined as first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline without administration of rescue intravenous glucose. The outcome measure used a Kaplan-Meier estimate with 95% confidence interval. Treatment groups without censoring utilized a distribution free method to compute the confidence interval for median time.

Full analysis set of all randomized patients who received at least one dose of trial product

Posted

Median

95% Confidence Interval

minutes

0-45 minutes after dosing

ID	Title	Description
OG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
OG001	Placebo	Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon
OG002	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon

Units	Counts
Participants	OG00082 OG00143 OG00243

Title

Denominators

Categories

Title	Measurements
	OG00010(10 to 10) OG00140(30 to 40) OG00212(10 to 12)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The treatment group difference between dasiglucagon and placebo was evaluated inferentially using a pairwise two-sided log rank test. Kaplan-Meier estimate with 95% CI, p-value based on treatment group difference between dasiglucagon and placebo using a two-sided log-rank test stratified by injection site. Treatment groups without censoring utilized a distribution free method to compute the confidence interval for median time.	Log Rank		<0.001														Superiority

Secondary

Plasma Glucose Recovery

Plasma glucose recovery within 30 minutes, within 20 minutes, within 15 minutes, and within 10 minutes after study drug injection without administration of rescue IV glucose. Plasma glucose recovery was defined as the first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline without administration of rescue intravenous glucose.

Full analysis set of all randomized patients who received at least one dose of trial product

Posted

Count of Participants

Participants

0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection

ID	Title	Description
OG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
OG001	Placebo	Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon
OG002	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon

Units

Secondary

Plasma Glucose Changes From Baseline

Plasma glucose changes from baseline at 30 minutes, 20 minutes, 15 minutes and 10 minutes after study drug injection without administration of rescue intravenous glucose

Full analysis set of all randomized patients who received at least one dose of trial product

Posted

Mean

Standard Deviation

mg/dL

0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection

ID	Title	Description
OG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
OG001	Placebo	Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon
OG002	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon

Units	Counts
Participants

Secondary

Time to Target

Time to first plasma glucose concentration ≥70 mg/dL (3.9 mmol/L) without administration of rescue intravenous glucose. The outcome measure used a Kaplan-Meier estimate with 95% confidence interval. Treatment groups without censoring utilized a distribution free method to compute the confidence interval for median time.

Full analysis set of all randomized patients who received at least one dose of trial product

Posted

Median

95% Confidence Interval

minutes

0-45 minutes after dosing

ID	Title	Description
OG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
OG001	Placebo	Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon
OG002	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon

Units	Counts
Participants

Secondary

Pharmacodynamics - Area Under the Effect Curve

Plasma glucose response as area under the effect curve (AUE) above baseline from time zero to 30 minutes. Samples were collected pre-dose, and at 4, 6, 8, 10, 12, 15, 17, 20, 25 and 30 minutes after dosing.

Full analysis set of all randomized patients who received at least one dose of trial product

Posted

Mean

Standard Deviation

mg*h/dL

0-30 minutes after dosing

ID	Title	Description
OG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
OG001	Placebo	Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon
OG002	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon

Units	Counts
Participants

Secondary

Pharmacokinetics - Area Under the Plasma Concentration Curve

Area under the drug concentration curve from time zero to 90 minutes, AUC0-90min. To calculate the AUC the standard trapezoidal method was used, based on actual rather than nominal time points. Samples were collected pre-dose, and at 15, 30, 35, 40, 50, 60, 90 and 120 minutes after dosing.

Full analysis set of all randomized patients who received at least one dose of trial product. No results are presented for the placebo group, as no active drug was given in this group.

Posted

Geometric Mean

Geometric Coefficient of Variation

pmol*h/L

0-90 minutes after dosing

ID	Title	Description
OG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
OG001	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics - Area Under the Plasma Concentration Curve

Area under the drug concentration curve from time zero to 120 minutes, AUC0-120min. To calculate the AUC the standard trapezoidal method was used, based on actual rather than nominal time points. Samples were collected pre-dose, and at 15, 30, 35, 40, 50, 60, 90 and 120 minutes after dosing.

Full analysis set of all randomized patients who received at least one dose of trial product. No results are presented for the placebo group, as no active drug was given in this group.

Posted

Geometric Mean

Geometric Coefficient of Variation

pmol*h/L

0-120 minutes after dosing

ID	Title	Description
OG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
OG001	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics - Maximum Plasma Concentration

Maximum plasma drug concentration (Cmax). Maximum plasma drug concentration was determined as the maximum of all valid plasma dasiglucagon/glucagon concentrations. Samples were collected pre-dose, and at 15, 30, 35, 40, 50, 60, 90 and 120 minutes after dosing.

Full analysis set of all randomized patients who received at least one dose of trial product. No results are presented for the placebo group, as no active drug was given in this group.

Posted

Geometric Mean

Geometric Coefficient of Variation

pmol/L

0-120 minutes after dosing

ID	Title	Description
OG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
OG001	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics - Time to Maximum Plasma Concentration

Time to maximum plasma drug concentration (tmax). Median Tmax was determined as the time point where the maximum of all valid plasma dasiglucagon/glucagon concentration measurements for each measurement series was observed. Samples were collected pre-dose, and at 15, 30, 35, 40, 50, 60, 90 and 120 minutes after dosing.

Full analysis set of all randomized patients who received at least one dose of trial product. No results are presented for the placebo group, as no active drug was given in this group.

Posted

Median

Full Range

hours

0-120 minutes after dosing

ID	Title	Description
OG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
OG001	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon

Units	Counts
Participants	OG000

Secondary

Immunogenicity - Occurence of Anti-drug Antibodies

Occurence of antibodies against dasiglucagon/GlucaGen

The safety analysis set of all randomized patients who received trial medication (which was the same as the full analysis set)

Posted

Count of Participants

Participants

28 days

ID	Title	Description
OG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
OG001	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon

Units	Counts
Participants	OG000

Secondary

Rescue Infusion of IV Glucose During the Hypoglycemic Clamp Procedure

Number of patients receiving administration of rescue infusion of IV glucose during the hypoglycemic clamp procedure. IV = intravenous

The safety analysis set of all randomized patients who received trial medication (which was the same as the full analysis set)

Posted

Count of Participants

Participants

0-45 minutes after dosing

ID	Title	Description
OG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
OG001	Placebo	Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon
OG002	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon

Units	Counts
Participants

Secondary

Time to First Rescue Infusion of IV Glucose

Time to first rescue administration of rescue infusion of IV glucose. IV = intravenous

No patients received IV glucose infusions therefore there are no data available for this outcome measure

Posted

0-45 minutes after dosing

ID	Title	Description
OG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog
OG001	Placebo	Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon
OG002	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG00010 events10 affected82 at risk EG0012 events2 affected43 at risk EG0025 events5 affected43 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00046 events45 affected82 at risk EG0011 events1 affected43 at risk EG00224 events23 affected43 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00025 events19 affected82 at risk EG0011 events1 affected43 at risk EG00211 events9 affected43 at risk
Hypoglycemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG00039 events23 affected82 at risk EG0016 events5 affected43 at risk EG00210 events9 affected43 at risk
Nasopharyngitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0005 events5 affected82 at risk EG0011 events1 affected43 at risk EG0020 events0 affected43 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0004 events4 affected82 at risk EG0010 events0 affected43 at risk EG0021 events1 affected43 at risk
Anemia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected82 at risk EG0010 events0 affected43 at risk EG0021 events1 affected43 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected43 at risk EG0020 events0 affected43 at risk
Bradycardia	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected82 at risk EG0010 events0 affected43 at risk EG0021 events1 affected43 at risk
Asthenopia	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Abdominal tenderness	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Hypoesthesia oral	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected43 at risk EG0020 events0 affected43 at risk
Infusion site rash	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Injection site erythema	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0012 events2 affected43 at risk EG0022 events2 affected43 at risk
Injection site edema	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected82 at risk EG0010 events0 affected43 at risk EG0021 events1 affected43 at risk
Injection site pain	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Pyrexia	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Seasonal allergy	Immune system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Ear infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Gastroenteritis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected43 at risk EG0020 events0 affected43 at risk
Pharyngitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Sinusitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected43 at risk EG0020 events0 affected43 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Ketosis	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0021 events1 affected43 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected82 at risk EG0010 events0 affected43 at risk EG0021 events1 affected43 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected43 at risk EG0020 events0 affected43 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected82 at risk EG0010 events0 affected43 at risk EG0021 events1 affected43 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0011 events1 affected43 at risk EG0020 events0 affected43 at risk
Burning sensation	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Dizziness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected82 at risk EG0010 events0 affected43 at risk EG0022 events2 affected43 at risk
Presyncope	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Dysmenorrhea	Reproductive system and breast disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Hot flush	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected82 at risk EG0010 events0 affected43 at risk EG0021 events1 affected43 at risk
Thrombophlebitis	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected43 at risk EG0020 events0 affected43 at risk

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D003920	Diabetes Mellitus
D004700	Endocrine System Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D004763	Glucagon-Like Peptides
D052336	Proglucagon
D005768	Gastrointestinal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dasiglucagon 0.6 mg	Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	82	82	66	82
EG001	Placebo	Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	43	43	14	43
EG002	GlucaGen® 1.0 mg	Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon	43	43	32	43