Trial Outcomes & Findings for A Study to Assess the Pharmacodynamics of Lemborexant in Korean Participants With Insomnia Disorder (NCT NCT05594589)

Last Updated: 2025-07-03

Results Overview

LPS is the duration of time measured from lights off to the first epoch of 20 consecutive epochs of non-wakefulness as measured by polysomnography (PSG).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

Baseline, at Day 30

Results posted on

2025-07-03

Participant Flow

Participants took part in the study at 9 investigative sites in South Korea from 30 November 2022 to 24 May 2024.

A total of 183 participants were screened, of which 118 were screen failure, and 65 participants received placebo in Run-in Period. Participants who completed Run-in period were randomized in Treatment Period to receive placebo, lemborexant 5 milligrams (mg) or lemborexant 10 mg.

Participant milestones

Participant milestones
Measure	Placebo Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 5 mg Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 10 mg Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.
Overall Study STARTED	13	26	26
Overall Study Treated During Treatment Period	13	26	26
Overall Study Placebo Run-in Period	65	0	0
Overall Study COMPLETED	13	25	26
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 5 mg Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 10 mg Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.
Overall Study Other	0	1	0

Baseline Characteristics

A Study to Assess the Pharmacodynamics of Lemborexant in Korean Participants With Insomnia Disorder

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline, at Day 30

Population: The full analysis set (FAS) included the group of randomized participants who received at least 1 dose of randomized study drug and had LPS data from the PSG on Day 30.

LPS is the duration of time measured from lights off to the first epoch of 20 consecutive epochs of non-wakefulness as measured by polysomnography (PSG).

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 5 mg n=25 Participants Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 10 mg Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.
Treatment Period: Change From Baseline in Latency to Persistent Sleep (LPS) on Day 30 of Lemborexant 5 mg Compared to Placebo	-46.12 minutes Standard Deviation 59.006	-50.90 minutes Standard Deviation 55.263	—

SECONDARY outcome

Timeframe: Baseline, at Day 30

Population: The FAS included the group of randomized participants who received at least 1 dose of randomized study drug and had LPS data from the PSG on Day 30.

LPS is the duration of time measured from lights off to the first epoch of 20 consecutive epochs of non-wakefulness as measured by PSG.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 5 mg n=26 Participants Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 10 mg Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.
Treatment Period: Change From Baseline in LPS on Day 30 of Lemborexant 10 mg Compared to Placebo	-46.12 minutes Standard Deviation 59.006	-44.15 minutes Standard Deviation 68.632	—

SECONDARY outcome

Timeframe: Baseline, at Day 30

Population: The FAS included the group of randomized participants who received at least 1 dose of randomized study drug and had LPS data from the PSG on Day 30.

SE is defined as total sleep time (TST) divided by time spent in bed multiplied by 100 as measured by PSG. TST is duration of sleep from sleep onset until terminal awakening.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 5 mg n=25 Participants Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 10 mg Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.
Treatment Period: Change From Baseline in Objective Sleep Efficiency (SE) on Day 30 of Lemborexant 5 mg Compared to Placebo	8.32 percentage of time in bed asleep Standard Deviation 14.730	15.06 percentage of time in bed asleep Standard Deviation 12.292	—

SECONDARY outcome

Timeframe: Baseline, at Day 30

Population: The FAS included the group of randomized participants who received at least 1 dose of randomized study drug and had LPS data from the PSG on Day 30.

SE is defined as TST divided by time spent in bed multiplied by 100 as measured by PSG. TST is duration of sleep from sleep onset until terminal awakening.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 5 mg n=26 Participants Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 10 mg Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.
Treatment Period: Change From Baseline in Objective SE on Day 30 of Lemborexant 10 mg Compared to Placebo	8.32 percentage of time in bed asleep Standard Deviation 14.730	15.44 percentage of time in bed asleep Standard Deviation 13.160	—

SECONDARY outcome

Timeframe: From start of study drug administration at Day 1 up to Day 58

Population: The safety analysis set included participants who received at least 1 dose of randomized study drug and had at least 1 post-dose safety assessment.

A TEAE was defined as an adverse event (AE) that emerges during treatment (on or after the first dose of study drug up to 28 days after the participant's last dose), having been absent at pretreatment (Baseline) or reemerges during treatment, having been present at pretreatment but stopped before treatment, or worsens in severity during treatment relative to the pretreatment state, when the AE was continuous.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 5 mg n=26 Participants Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 10 mg n=26 Participants Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.
Treatment Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)	1 Participants	5 Participants	2 Participants

SECONDARY outcome

Timeframe: From start of study drug administration at Day 1 up to Day 58

Population: The safety analysis set included participants who received at least 1 dose of randomized study drug and had at least 1 post-dose safety assessment.

The laboratory parameters included hematology, chemistry, and urinalysis. Any abnormality in the laboratory results which are deemed clinically significant by the investigator were reported.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 5 mg n=26 Participants Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 10 mg n=26 Participants Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.
Treatment Period: Number of Participants With Clinically Significant Abnormal Laboratory Parameters	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From start of study drug administration at Day 1 up to Day 58

Population: The safety analysis set included participants who received at least 1 dose of randomized study drug and had at least 1 post-dose safety assessment.

Vital sign measurement included systolic and diastolic blood pressure, pulse rate, respiratory rate and body temperature. Any abnormality in vital signs which are deemed clinically significant by the investigator were reported.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 5 mg n=26 Participants Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 10 mg n=26 Participants Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.
Treatment Period: Number of Participants With Clinically Significant Abnormal Vital Signs Values	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From start of study drug administration at Day 1 up to Day 58

Population: The safety analysis set included participants who received at least 1 dose of randomized study drug and had at least 1 post-dose safety assessment.

Any abnormality in ECG assessments which were deemed clinically significant by the investigator were reported.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 5 mg n=26 Participants Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 10 mg n=26 Participants Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.
Treatment Period: Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) Findings	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Within 2 hours pre-dose on Day 30; At 1 and 1.5 hours after morning waketime on Day 31

Population: The pharmacokinetic (PK) analysis set included the group of participants who had at least 1 quantifiable plasma concentration of lemborexant or its metabolites, with adequately documented dosing history.

Plasma concentrations of lemborexant and its metabolites M4, M9, and M10 were reported.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 5 mg n=26 Participants Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 10 mg Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.
Treatment Period: Plasma Concentrations of Lemborexant and Its Metabolites (M4, M9, and M10) M10, Day 31: At 1 hour after morning waketime	3.64 nanogram per milliliter (ng/mL) Standard Deviation 2.17	9.04 nanogram per milliliter (ng/mL) Standard Deviation 5.51	—
Treatment Period: Plasma Concentrations of Lemborexant and Its Metabolites (M4, M9, and M10) M4, Day 31: At 1.5 hour after morning waketime	6.58 nanogram per milliliter (ng/mL) Standard Deviation 2.76	14.1 nanogram per milliliter (ng/mL) Standard Deviation 5.76	—
Treatment Period: Plasma Concentrations of Lemborexant and Its Metabolites (M4, M9, and M10) Lemborexant, Day 30: Pre-dose	4.00 nanogram per milliliter (ng/mL) Standard Deviation 6.20	9.13 nanogram per milliliter (ng/mL) Standard Deviation 10.3	—
Treatment Period: Plasma Concentrations of Lemborexant and Its Metabolites (M4, M9, and M10) M4, Day 30: Pre-dose	2.10 nanogram per milliliter (ng/mL) Standard Deviation 2.68	5.60 nanogram per milliliter (ng/mL) Standard Deviation 5.87	—
Treatment Period: Plasma Concentrations of Lemborexant and Its Metabolites (M4, M9, and M10) M9, Day 30: Pre-dose	0.501 nanogram per milliliter (ng/mL) Standard Deviation 0.622	1.33 nanogram per milliliter (ng/mL) Standard Deviation 1.48	—
Treatment Period: Plasma Concentrations of Lemborexant and Its Metabolites (M4, M9, and M10) M10, Day 30: Pre-dose	1.86 nanogram per milliliter (ng/mL) Standard Deviation 2.22	5.43 nanogram per milliliter (ng/mL) Standard Deviation 5.51	—
Treatment Period: Plasma Concentrations of Lemborexant and Its Metabolites (M4, M9, and M10) Lemborexant, Day 31: At 1 hour after morning waketime	7.72 nanogram per milliliter (ng/mL) Standard Deviation 4.45	17.9 nanogram per milliliter (ng/mL) Standard Deviation 10.3	—
Treatment Period: Plasma Concentrations of Lemborexant and Its Metabolites (M4, M9, and M10) M4, Day 31: At 1 hour after morning waketime	6.80 nanogram per milliliter (ng/mL) Standard Deviation 2.67	14.6 nanogram per milliliter (ng/mL) Standard Deviation 5.93	—
Treatment Period: Plasma Concentrations of Lemborexant and Its Metabolites (M4, M9, and M10) M9, Day 31: At 1 hour after morning waketime	1.42 nanogram per milliliter (ng/mL) Standard Deviation 0.589	3.27 nanogram per milliliter (ng/mL) Standard Deviation 1.50	—
Treatment Period: Plasma Concentrations of Lemborexant and Its Metabolites (M4, M9, and M10) Lemborexant, Day 31: At 1.5 hour after morning waketime	7.40 nanogram per milliliter (ng/mL) Standard Deviation 4.36	17.1 nanogram per milliliter (ng/mL) Standard Deviation 10.0	—
Treatment Period: Plasma Concentrations of Lemborexant and Its Metabolites (M4, M9, and M10) M9, Day 31: At 1.5 hour after morning waketime	1.38 nanogram per milliliter (ng/mL) Standard Deviation 0.573	3.14 nanogram per milliliter (ng/mL) Standard Deviation 1.46	—
Treatment Period: Plasma Concentrations of Lemborexant and Its Metabolites (M4, M9, and M10) M10, Day 31: At 1.5 hour after morning waketime	3.67 nanogram per milliliter (ng/mL) Standard Deviation 2.20	8.80 nanogram per milliliter (ng/mL) Standard Deviation 5.29	—

Adverse Events

Run-in Period: Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Treatment Period: Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Treatment Period: Lemborexant 5 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Treatment Period: Lemborexant 10 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Serena SoYoun Kwon

Eisai Korea Inc. Medical department

Phone: +82-2-3451-5533

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=13 Participants Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 5 mg n=26 Participants Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Lemborexant 10 mg n=26 Participants Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Total n=65 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	26 Participants n=7 Participants	26 Participants n=5 Participants	65 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
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	20 Participants n=7 Participants	25 Participants n=5 Participants	57 Participants n=4 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Age, Continuous	38.6 years STANDARD_DEVIATION 13.33 • n=5 Participants	49.1 years STANDARD_DEVIATION 15.85 • n=7 Participants	43.2 years STANDARD_DEVIATION 13.84 • n=5 Participants	46.2 years STANDARD_DEVIATION 15.03 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	13 Participants n=7 Participants	17 Participants n=5 Participants	40 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	13 Participants n=7 Participants	9 Participants n=5 Participants	25 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	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	13 Participants n=5 Participants	26 Participants n=7 Participants	26 Participants n=5 Participants	65 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (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

Measure	Run-in Period: Placebo n=65 participants at risk Participants received one lemborexant-matched PBO tablet, orally, once daily, approximately 5 minutes before intend to sleep for 14 nights from Day -14 up to Baseline (Day 1) during Run-in Period.	Treatment Period: Placebo n=13 participants at risk Participants received one lemborexant-matched placebo tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Treatment Period: Lemborexant 5 mg n=26 participants at risk Participants received one lemborexant 5 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.	Treatment Period: Lemborexant 10 mg n=26 participants at risk Participants received one lemborexant 10 mg tablet, orally, once daily, approximately 5 minutes before intend to sleep for 30 nights from Day 1 up to Day 30 in Treatment Period.
Cardiac disorders Postural orthostatic tachycardia syndrome	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Gastrointestinal disorders Dyspepsia	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Gastrointestinal disorders Constipation	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	7.7% 1/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
General disorders Oedema peripheral	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Metabolism and nutrition disorders Dyslipidaemia	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.5% 1/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	1.5% 1/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Nervous system disorders Syncope	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Vascular disorders Arteriosclerosis	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)
Vascular disorders Orthostatic hypotension	0.00% 0/65 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/13 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	3.8% 1/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)	0.00% 0/26 • Run-in Period: From first dose in Run-in Period at Day -14 up to Baseline (Day 1); Treatment Period: From first dose in Treatment Period at Day 1 up to end of follow-up period (up to Day 58)