Trial Outcomes & Findings for PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea and Vomiting (NCT NCT03204279)

NCT ID: NCT03204279

Last Updated: 2024-06-25

Results Overview

Mean values of area under the plasma Concentration versus time curve from time zero to infinity (AUC0-inf) of netupitant after a single oral netupitant administration, concomitantly with oral palonosetron, in pediatric cancer patients receiving HEC or MEC cycles. AUC estimates are obtained by non-compartmental analysis of population model-predicted individual plasma concentration-time profiles.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

within 168 hours after netupitant administration. A sampling windows approach will be used by collecting a single blood sample from each patient in one of these time windows: from 2 to 8 h, from 24 to 48 h, from 72 to 96 h and from 120 to 168 h.

Results posted on

2024-06-25

Participant Flow

Participant milestones

Participant milestones
Measure	Netupitant 1.33 mg/kg Plus Palonosetron Single oral dose of Netupitant 1.33 mg/kg up to a maximum of 100 mg (for patients \< 3 months of age the netupitant dose will be 0.8 mg/kg) administered with single oral dose of 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 1.33 mg/kg oral suspension up to a maximum of 100 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg	Netupitant 4 mg/kg Plus Palonosetron Single oral dose of Netupitant 4 mg/kg up to a maximum of 300 mg (for patients \< 3 months of age the netupitant dose will be 2.4 mg/kg) administered with single oral dose 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 4 mg/kg oral suspension up to a maximum of 300 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg
Overall Study STARTED	34	33
Overall Study COMPLETED	34	32
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Netupitant 1.33 mg/kg Plus Palonosetron Single oral dose of Netupitant 1.33 mg/kg up to a maximum of 100 mg (for patients \< 3 months of age the netupitant dose will be 0.8 mg/kg) administered with single oral dose of 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 1.33 mg/kg oral suspension up to a maximum of 100 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg	Netupitant 4 mg/kg Plus Palonosetron Single oral dose of Netupitant 4 mg/kg up to a maximum of 300 mg (for patients \< 3 months of age the netupitant dose will be 2.4 mg/kg) administered with single oral dose 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 4 mg/kg oral suspension up to a maximum of 300 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea and Vomiting

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Netupitant 1.33 mg/kg Plus Palonosetron n=34 Participants Single oral dose of Netupitant 1.33 mg/kg up to a maximum of 100 mg (for patients \< 3 months of age the netupitant dose will be 0.8 mg/kg) administered with single oral dose of 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 1.33 mg/kg oral suspension up to a maximum of 100 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg	Netupitant 4 mg/kg Plus Palonosetron n=32 Participants Single oral dose of Netupitant 4 mg/kg up to a maximum of 300 mg (for patients \< 3 months of age the netupitant dose will be 2.4 mg/kg) administered with single oral dose 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 4 mg/kg oral suspension up to a maximum of 300 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg	Total n=66 Participants Total of all reporting groups
Age, Continuous	6.6 years STANDARD_DEVIATION 6.29 • n=99 Participants	5.6 years STANDARD_DEVIATION 5.46 • n=107 Participants	6.1 years STANDARD_DEVIATION 5.88 • n=206 Participants
Age, Customized 3 to <6 months	3 Participants n=99 Participants	2 Participants n=107 Participants	5 Participants n=206 Participants
Age, Customized 6 to <12 months	4 Participants n=99 Participants	5 Participants n=107 Participants	9 Participants n=206 Participants
Age, Customized 1 to <2 years	3 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants
Age, Customized 2 to <5 years	6 Participants n=99 Participants	6 Participants n=107 Participants	12 Participants n=206 Participants
Age, Customized 5 to <12 years	8 Participants n=99 Participants	8 Participants n=107 Participants	16 Participants n=206 Participants
Age, Customized 12 to <18 years	9 Participants n=99 Participants	7 Participants n=107 Participants	16 Participants n=206 Participants
Age, Customized 1 to <3 months	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Sex: Female, Male Female	13 Participants n=99 Participants	14 Participants n=107 Participants	27 Participants n=206 Participants
Sex: Female, Male Male	21 Participants n=99 Participants	18 Participants n=107 Participants	39 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	34 Participants n=99 Participants	31 Participants n=107 Participants	65 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants

PRIMARY outcome

Timeframe: within 168 hours after netupitant administration. A sampling windows approach will be used by collecting a single blood sample from each patient in one of these time windows: from 2 to 8 h, from 24 to 48 h, from 72 to 96 h and from 120 to 168 h.

Population: Pediatric patients divided in seven age groups; in netupitant 4 mg/kg arm 1 patient was withdrew from the study after randomization of study drug and was not treated; 1 patient was treated with study drug but did not receive the entire planned dose and was not included in this analysis and one patient received the entire planned dose, but did not have any measurable concentration of netupitant and/or palonosetron.

Outcome measures

Outcome measures
Measure	Netupitant 1.33 mg/kg Plus Palonosetron n=34 Participants Single oral dose of Netupitant 1.33 mg/kg up to a maximum of 100 mg (for patients \< 3 months of age the netupitant dose will be 0.8 mg/kg) administered with single oral dose of 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 1.33 mg/kg oral suspension up to a maximum of 100 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg	Netupitant 4 mg/kg Plus Palonosetron n=30 Participants Single oral dose of Netupitant 4 mg/kg up to a maximum of 300 mg (for patients \< 3 months of age the netupitant dose will be 2.4 mg/kg) administered with single oral dose 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 4 mg/kg oral suspension up to a maximum of 300 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Netupitant patients 1 month to <3 months of age	4460 ng*hr/mL	—
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Netupitant patients 3 month to <6 months of age	3849 ng*hr/mL Standard Deviation 91.3	17340 ng*hr/mL Standard Deviation 36.4
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Netupitant patients 6 month to <1 year of age	7637 ng*hr/mL Standard Deviation 113	8617 ng*hr/mL Standard Deviation 45.2
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Netupitant patients 1 year to <2 years	2276 ng*hr/mL Standard Deviation 29.8	9886 ng*hr/mL Standard Deviation 59.6
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Netupitant patients 2 years to <5 years	3135 ng*hr/mL Standard Deviation 44.0	14404 ng*hr/mL Standard Deviation 131
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Netupitant patients 5 years to <12 years	2676 ng*hr/mL Standard Deviation 35.0	10154 ng*hr/mL Standard Deviation 70.7
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Netupitant patients 12 years to <18 years	3107 ng*hr/mL Standard Deviation 54.9	12266 ng*hr/mL Standard Deviation 26.9

PRIMARY outcome

Mean values of maximum plasma concentration (Cmax) of netupitant after a single oral netupitant administration, concomitantly with oral palonosetron, in pediatric cancer patients receiving HEC or MEC cycles. Cmax estimates are obtained by non-compartmental analysis of population model-predicted individual plasma concentration-time profiles

Outcome measures

Outcome measures
Measure	Netupitant 1.33 mg/kg Plus Palonosetron n=34 Participants Single oral dose of Netupitant 1.33 mg/kg up to a maximum of 100 mg (for patients \< 3 months of age the netupitant dose will be 0.8 mg/kg) administered with single oral dose of 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 1.33 mg/kg oral suspension up to a maximum of 100 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg	Netupitant 4 mg/kg Plus Palonosetron n=30 Participants Single oral dose of Netupitant 4 mg/kg up to a maximum of 300 mg (for patients \< 3 months of age the netupitant dose will be 2.4 mg/kg) administered with single oral dose 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 4 mg/kg oral suspension up to a maximum of 300 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg
Maximum Plasma Concentration (Cmax) of Netupitant 1 month to <3 months	60.8 ng/mL Standard Deviation NA For only one measurement CV is not available	—
Maximum Plasma Concentration (Cmax) of Netupitant 3 months to <6 months	76.0 ng/mL Standard Deviation 27.1	233 ng/mL Standard Deviation 4.25
Maximum Plasma Concentration (Cmax) of Netupitant 6 months to <12 months	133 ng/mL Standard Deviation 71.7	255 ng/mL Standard Deviation 31.2
Maximum Plasma Concentration (Cmax) of Netupitant 1 year to <2 years	69.5 ng/mL Standard Deviation 19.3	275 ng/mL Standard Deviation 38.2
Maximum Plasma Concentration (Cmax) of Netupitant 2 years to <5 years	74.0 ng/mL Standard Deviation 32.3	266 ng/mL Standard Deviation 55.0
Maximum Plasma Concentration (Cmax) of Netupitant 5 years to <12 years	67.9 ng/mL Standard Deviation 32.1	213 ng/mL Standard Deviation 20.1
Maximum Plasma Concentration (Cmax) of Netupitant 12 years to <18 years	76.8 ng/mL Standard Deviation 27.3	274 ng/mL Standard Deviation 15.6

PRIMARY outcome

Timeframe: > 24-120 hours after the start of chemotherapy on Day 1

Population: All pediatric patients with exposures parameters and CR data in the delayed phase

Exposure - Response analysis for netupitant performed by assessing the relationships between exposure parameters AUC0-inf and Cmax with the primary efficacy endpoint, i.e., the CR in the delayed phase. Graphical exposure-response analysis for netupitant performed by assessing the relationship between individual exposure parameters (AUC0-inf) and Cmax) with the primary efficacy endpoint, i.e the CR in the delayed phase.

Outcome measures

Outcome measures
Measure	Netupitant 1.33 mg/kg Plus Palonosetron n=64 Participants Single oral dose of Netupitant 1.33 mg/kg up to a maximum of 100 mg (for patients \< 3 months of age the netupitant dose will be 0.8 mg/kg) administered with single oral dose of 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 1.33 mg/kg oral suspension up to a maximum of 100 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg	Netupitant 4 mg/kg Plus Palonosetron Single oral dose of Netupitant 4 mg/kg up to a maximum of 300 mg (for patients \< 3 months of age the netupitant dose will be 2.4 mg/kg) administered with single oral dose 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 4 mg/kg oral suspension up to a maximum of 300 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg
Exposure - Response Analysis for Netupitant number of participants with CR in delayed phase	45 Participants	—
Exposure - Response Analysis for Netupitant number of participants with no CR in delayed phase	19 Participants	—

SECONDARY outcome

Timeframe: > 24-120 hours after the start of chemotherapy on Day 1

Percentage of Pediatric Patients with complete response (CR, i.e., no emetic episodes and no rescue medication) during the delayed phase (\> 24 to 120 h after the start of chemotherapy on Day 1) after a single oral netupitant administration, concomitantly with oral palonosetron, in pediatric cancer patients receiving HEC or MEC cycles.

Outcome measures

Outcome measures
Measure	Netupitant 1.33 mg/kg Plus Palonosetron n=34 Participants Single oral dose of Netupitant 1.33 mg/kg up to a maximum of 100 mg (for patients \< 3 months of age the netupitant dose will be 0.8 mg/kg) administered with single oral dose of 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 1.33 mg/kg oral suspension up to a maximum of 100 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg	Netupitant 4 mg/kg Plus Palonosetron n=31 Participants Single oral dose of Netupitant 4 mg/kg up to a maximum of 300 mg (for patients \< 3 months of age the netupitant dose will be 2.4 mg/kg) administered with single oral dose 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 4 mg/kg oral suspension up to a maximum of 300 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg
Percentage of Pediatric Patients With Complete Response During the Delayed Phase	24 Participants	22 Participants

Adverse Events

Netupitant 1.33 mg/kg Plus Palonosetron

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Netupitant 4 mg/kg Plus Palonosetron

Serious events: 3 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Netupitant 1.33 mg/kg Plus Palonosetron n=34 participants at risk Single oral dose of Netupitant 1.33 mg/kg up to a maximum of 100 mg (for patients \< 3 months of age the netupitant dose will be 0.8 mg/kg) administered with single oral dose of 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 1.33 mg/kg oral suspension up to a maximum of 100 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg	Netupitant 4 mg/kg Plus Palonosetron n=32 participants at risk Single oral dose of Netupitant 4 mg/kg up to a maximum of 300 mg (for patients \< 3 months of age the netupitant dose will be 2.4 mg/kg) administered with single oral dose 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 4 mg/kg oral suspension up to a maximum of 300 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/34 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	6.2% 2/32 • Number of events 2 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Gastrointestinal disorders Stomatitis	0.00% 0/34 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	3.1% 1/32 • Number of events 1 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Infections and infestations Neutropenic sepsis	0.00% 0/34 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	3.1% 1/32 • Number of events 1 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Infections and infestations Urinary tract infection	0.00% 0/34 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	3.1% 1/32 • Number of events 1 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])

Other adverse events

Additional Information

Edwin de Wit - Head of Clinical Development

Helsinn Healthcare SA

Phone: +41 91 985 2121

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Netupitant 1.33 mg/kg Plus Palonosetron n=34 participants at risk Single oral dose of Netupitant 1.33 mg/kg up to a maximum of 100 mg (for patients \< 3 months of age the netupitant dose will be 0.8 mg/kg) administered with single oral dose of 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 1.33 mg/kg oral suspension up to a maximum of 100 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg	Netupitant 4 mg/kg Plus Palonosetron n=32 participants at risk Single oral dose of Netupitant 4 mg/kg up to a maximum of 300 mg (for patients \< 3 months of age the netupitant dose will be 2.4 mg/kg) administered with single oral dose 20 μg/kg palonosetron up to a maximum of 1.5 mg. Netupitant: Netupitant 4 mg/kg oral suspension up to a maximum of 300 mg Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg
Blood and lymphatic system disorders Anaemia	26.5% 9/34 • Number of events 9 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	21.9% 7/32 • Number of events 8 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Blood and lymphatic system disorders Febrile neutropenia	5.9% 2/34 • Number of events 2 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	9.4% 3/32 • Number of events 3 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Blood and lymphatic system disorders Leukopenia	23.5% 8/34 • Number of events 8 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	12.5% 4/32 • Number of events 5 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Blood and lymphatic system disorders Neutropenia	8.8% 3/34 • Number of events 3 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	18.8% 6/32 • Number of events 6 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Blood and lymphatic system disorders Thrombocytopenia	29.4% 10/34 • Number of events 10 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	18.8% 6/32 • Number of events 7 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Gastrointestinal disorders Nausea	2.9% 1/34 • Number of events 1 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	6.2% 2/32 • Number of events 2 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Gastrointestinal disorders Stomatitis	5.9% 2/34 • Number of events 2 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	15.6% 5/32 • Number of events 5 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Gastrointestinal disorders Vomiting	5.9% 2/34 • Number of events 2 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	9.4% 3/32 • Number of events 4 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
General disorders Complication associated with device	2.9% 1/34 • Number of events 1 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	3.1% 1/32 • Number of events 2 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
General disorders Pyrexia	2.9% 1/34 • Number of events 2 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	15.6% 5/32 • Number of events 5 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Investigations Alanine aminotransferase increased	8.8% 3/34 • Number of events 3 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	3.1% 1/32 • Number of events 1 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Investigations Aspartate aminotransferase increased	5.9% 2/34 • Number of events 2 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	0.00% 0/32 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Investigations White blood cell count decreased	5.9% 2/34 • Number of events 2 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	3.1% 1/32 • Number of events 1 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Metabolism and nutrition disorders Hypoglycaemia	5.9% 2/34 • Number of events 3 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	0.00% 0/32 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Nervous system disorders Headache	2.9% 1/34 • Number of events 1 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	6.2% 2/32 • Number of events 2 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])
Vascular disorders Hypertension	0.00% 0/34 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])	6.2% 2/32 • Number of events 2 • From the first dose of study drug on Visit 2 (Day 1, inclusively) until Visit 5 (follow up, Day 14 [+3])