Trial Outcomes & Findings for A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects (NCT NCT03378635)

NCT ID: NCT03378635

Last Updated: 2021-06-10

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 170 participants
• Primary outcome timeframe: 0-45 minutes after dosing
• Results posted on: 2021-06-10

Participant Flow

Participant milestones

Measure	Dasiglucagon 0.6 mg Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Overall Study STARTED	84	43	43
Overall Study Randomized and Exposed to Treatment	82	43	43
Overall Study COMPLETED	82	43	43
Overall Study NOT COMPLETED	2	0	0

Reasons for withdrawal

Measure	Dasiglucagon 0.6 mg Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Overall Study Adverse Event	1	0	0
Overall Study Withdrawal by Subject	1	0	0

Baseline Characteristics

A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects

Baseline characteristics by cohort

Measure	Dasiglucagon 0.6 mg n=82 Participants Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 Participants Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg n=43 Participants Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon	Total n=168 Participants Total of all reporting groups
Age, Continuous	39.2 years STANDARD_DEVIATION 12.1 • n=5 Participants	38.0 years STANDARD_DEVIATION 13.1 • n=7 Participants	40.2 years STANDARD_DEVIATION 11.5 • n=5 Participants	39.1 years STANDARD_DEVIATION 12.2 • n=4 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	16 Participants n=7 Participants	15 Participants n=5 Participants	63 Participants n=4 Participants
Sex: Female, Male Male	50 Participants n=5 Participants	27 Participants n=7 Participants	28 Participants n=5 Participants	105 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	80 Participants n=5 Participants	41 Participants n=7 Participants	40 Participants n=5 Participants	161 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) White	76 Participants n=5 Participants	39 Participants n=7 Participants	39 Participants n=5 Participants	154 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Canada	18 participants n=5 Participants	10 participants n=7 Participants	10 participants n=5 Participants	38 participants n=4 Participants
Region of Enrollment Austria	33 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	33 participants n=4 Participants
Region of Enrollment United States	12 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	24 participants n=4 Participants
Region of Enrollment Germany	19 participants n=5 Participants	27 participants n=7 Participants	27 participants n=5 Participants	73 participants n=4 Participants

PRIMARY outcome

Timeframe: 0-45 minutes after dosing

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

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.

Outcome measures

Measure	Dasiglucagon 0.6 mg n=82 Participants Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 Participants Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg n=43 Participants Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Time to Plasma Glucose Recovery	10 minutes Interval 10.0 to 10.0	40 minutes Interval 30.0 to 40.0	12 minutes Interval 10.0 to 12.0

SECONDARY outcome

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

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

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.

Outcome measures

Measure	Dasiglucagon 0.6 mg n=82 Participants Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 Participants Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg n=43 Participants Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Plasma Glucose Recovery Glucose recovery at 30 minutes	82 Participants	20 Participants	43 Participants
Plasma Glucose Recovery Glucose recovery at 20 minutes	81 Participants	6 Participants	42 Participants
Plasma Glucose Recovery Glucose recovery at 15 minutes	81 Participants	1 Participants	41 Participants
Plasma Glucose Recovery Glucose recovery at 10 minutes	53 Participants	0 Participants	21 Participants

SECONDARY outcome

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

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

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

Outcome measures

Measure	Dasiglucagon 0.6 mg n=82 Participants Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 Participants Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg n=43 Participants Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Plasma Glucose Changes From Baseline At 15 minutes	43.5 mg/dL Standard Deviation 12.51	6.65 mg/dL Standard Deviation 6.82	44.1 mg/dL Standard Deviation 14.0
Plasma Glucose Changes From Baseline At 30 minutes	90.9 mg/dL Standard Deviation 18.2	19.1 mg/dL Standard Deviation 13.0	88.5 mg/dL Standard Deviation 19.2
Plasma Glucose Changes From Baseline At 20 minutes	59.7 mg/dL Standard Deviation 15.0	8.7 mg/dL Standard Deviation 10.8	58.4 mg/dL Standard Deviation 15.6
Plasma Glucose Changes From Baseline At 10 minutes	23.9 mg/dL Standard Deviation 9.84	-0.14 mg/dL Standard Deviation 5.65	22.0 mg/dL Standard Deviation 10.0

SECONDARY outcome

Timeframe: 0-45 minutes after dosing

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

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.

Outcome measures

Measure	Dasiglucagon 0.6 mg n=82 Participants Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 Participants Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg n=43 Participants Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Time to Target	8 minutes Interval 8.0 to 8.0	25 minutes Interval 20.0 to 30.0	8 minutes Interval 8.0 to 10.0

SECONDARY outcome

Timeframe: 0-30 minutes after dosing

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

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.

Outcome measures

Measure	Dasiglucagon 0.6 mg n=82 Participants Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 Participants Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg n=43 Participants Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Pharmacodynamics - Area Under the Effect Curve	21.0 mg*h/dL Standard Deviation 5.26	3.57 mg*h/dL Standard Deviation 2.86	20.4 mg*h/dL Standard Deviation 5.49

SECONDARY outcome

Timeframe: 0-90 minutes after dosing

Population: 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.

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.

Outcome measures

Measure	Dasiglucagon 0.6 mg n=82 Participants Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 Participants Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Pharmacokinetics - Area Under the Plasma Concentration Curve	1430 pmol*h/L Geometric Coefficient of Variation 34.2	1300 pmol*h/L Geometric Coefficient of Variation 27.5	—

SECONDARY outcome

Timeframe: 0-120 minutes after dosing

Population: 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.

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.

Outcome measures

Measure	Dasiglucagon 0.6 mg n=82 Participants Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 Participants Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Pharmacokinetics - Area Under the Plasma Concentration Curve	1770 pmol*h/L Geometric Coefficient of Variation 31.2	1490 pmol*h/L Geometric Coefficient of Variation 27.2	—

SECONDARY outcome

Timeframe: 0-120 minutes after dosing

Population: 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.

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.

Outcome measures

Measure	Dasiglucagon 0.6 mg n=82 Participants Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 Participants Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Pharmacokinetics - Maximum Plasma Concentration	1280 pmol/L Geometric Coefficient of Variation 37.7	1490 pmol/L Geometric Coefficient of Variation 34.5	—

SECONDARY outcome

Timeframe: 0-120 minutes after dosing

Population: 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.

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.

Outcome measures

Measure	Dasiglucagon 0.6 mg n=82 Participants Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 Participants Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Pharmacokinetics - Time to Maximum Plasma Concentration	0.670 hours Interval 0.25 to 1.0	0.250 hours Interval 0.23 to 0.67	—

SECONDARY outcome

Timeframe: 28 days

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

Occurence of antibodies against dasiglucagon/GlucaGen

Outcome measures

Measure	Dasiglucagon 0.6 mg n=82 Participants Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 Participants Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Immunogenicity - Occurence of Anti-drug Antibodies Anti-drug antibodies at follow-up day 28	1 Participants	0 Participants	—
Immunogenicity - Occurence of Anti-drug Antibodies Anti-drug antibodies at second follow up	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: 0-45 minutes after dosing

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

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

Outcome measures

Measure	Dasiglucagon 0.6 mg n=82 Participants Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 Participants Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg n=43 Participants Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Rescue Infusion of IV Glucose During the Hypoglycemic Clamp Procedure	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 0-45 minutes after dosing

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

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

Outcome measures

Outcome data not reported

Adverse Events

Dasiglucagon 0.6 mg

Serious events: 0 serious events

Other events: 66 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

GlucaGen® 1.0 mg

Serious events: 0 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Dasiglucagon 0.6 mg n=82 participants at risk Single fixed dose (s.c.injection) of dasiglucagon Dasiglucagon: Glucagon analog	Placebo n=43 participants at risk Single fixed dose (s.c.injection) of placebo Placebo: Placebo for dasiglucagon	GlucaGen® 1.0 mg n=43 participants at risk Single fixed dose (s.c.injection) of GlucaGen® GlucaGen: Native glucagon
Nervous system disorders Headache	12.2% 10/82 • Number of events 10 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	4.7% 2/43 • Number of events 2 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	11.6% 5/43 • Number of events 5 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Gastrointestinal disorders Nausea	54.9% 45/82 • Number of events 46 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	53.5% 23/43 • Number of events 24 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Gastrointestinal disorders Vomiting	23.2% 19/82 • Number of events 25 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	20.9% 9/43 • Number of events 11 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Metabolism and nutrition disorders Hypoglycemia	28.0% 23/82 • Number of events 39 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	11.6% 5/43 • Number of events 6 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	20.9% 9/43 • Number of events 10 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Infections and infestations Nasopharyngitis	6.1% 5/82 • Number of events 5 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Gastrointestinal disorders Diarrhea	4.9% 4/82 • Number of events 4 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Blood and lymphatic system disorders Anemia	0.00% 0/82 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/82 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Cardiac disorders Bradycardia	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Ear and labyrinth disorders Vertigo	0.00% 0/82 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Eye disorders Asthenopia	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Gastrointestinal disorders Abdominal tenderness	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Gastrointestinal disorders Hypoesthesia oral	0.00% 0/82 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
General disorders Infusion site rash	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
General disorders Injection site erythema	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	4.7% 2/43 • Number of events 2 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	4.7% 2/43 • Number of events 2 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
General disorders Injection site edema	0.00% 0/82 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
General disorders Injection site pain	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
General disorders Pyrexia	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Immune system disorders Seasonal allergy	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Infections and infestations Ear infection	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Infections and infestations Gastroenteritis	0.00% 0/82 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Infections and infestations Pharyngitis	2.4% 2/82 • Number of events 2 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Infections and infestations Sinusitis	0.00% 0/82 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Metabolism and nutrition disorders Hyperglycaemia	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Metabolism and nutrition disorders Ketosis	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Metabolism and nutrition disorders Vitamin D deficiency	0.00% 0/82 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/82 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Musculoskeletal and connective tissue disorders Back pain	2.4% 2/82 • Number of events 2 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/82 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Musculoskeletal and connective tissue disorders Pain in extremity	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Nervous system disorders Burning sensation	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Nervous system disorders Dizziness	0.00% 0/82 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	4.7% 2/43 • Number of events 2 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Nervous system disorders Presyncope	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Renal and urinary disorders Pollakiuria	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Reproductive system and breast disorders Dysmenorrhea	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Respiratory, thoracic and mediastinal disorders Cough	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Vascular disorders Hot flush	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Vascular disorders Orthostatic hypotension	0.00% 0/82 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.
Vascular disorders Thrombophlebitis	1.2% 1/82 • Number of events 1 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.	0.00% 0/43 • Adverse events (AEs) were collected from the first trial-related activity after the patient had signed the informed consent to the end of the follow-up period, i.e. over 28 days All AEs, either observed by the investigator or reported by the patient, were recorded by the investigator and evaluated, including diagnosis, if possible. If no diagnosis was made, the investigator was to record each sign and symptom as individual AEs. Information included date and time of onset and resolution, date and time of investigator's first information on the AE, seriousness, severity, casual relationship with investigational product, interruption/withdrawal of treatment and outcome.

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