Trial Outcomes & Findings for An Efficacy and Safety Study of Paliperidone Palmitate in Participants With Schizophrenia (NCT NCT01299389)

NCT ID: NCT01299389

Last Updated: 2013-06-17

Results Overview

The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210, higher scores indicate worsening.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 323 participants
• Primary outcome timeframe: Baseline and Week 13 or early discontinuation
• Results posted on: 2013-06-17

Participant Flow

Participant milestones

Measure	Placebo (Double-blind) Matching Placebo was given intramuscularly (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64.	Paliperidone Palmitate (Double-blind) Paliperidone palmitate was given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64.	Placebo (Post-observational) Participants who completed double-blind period or discontinued early from double-blind period had follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants did not receive any study drug during post-observational period.	Paliperidone Palmitate (Post-observational) Participants who completed double-blind period or discontinued early from double-blind period had follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants did not receive any study drug during post-observational period.
Double-blind STARTED	164	159	0	0
Double-blind COMPLETED	55	95	0	0
Double-blind NOT COMPLETED	109	64	0	0
Post-observational STARTED	0	0	156	155
Post-observational COMPLETED	0	0	144	149
Post-observational NOT COMPLETED	0	0	12	6

Reasons for withdrawal

Measure	Placebo (Double-blind) Matching Placebo was given intramuscularly (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64.	Paliperidone Palmitate (Double-blind) Paliperidone palmitate was given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64.	Placebo (Post-observational) Participants who completed double-blind period or discontinued early from double-blind period had follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants did not receive any study drug during post-observational period.	Paliperidone Palmitate (Post-observational) Participants who completed double-blind period or discontinued early from double-blind period had follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants did not receive any study drug during post-observational period.
Double-blind Adverse Event	45	27	0	0
Double-blind Lack of Efficacy	45	21	0	0
Double-blind Lost to Follow-up	2	1	0	0
Double-blind Withdrawal by Subject	16	13	0	0
Double-blind Other	1	1	0	0
Double-blind fail to meet "study population" criteria	0	1	0	0
Post-observational Other	0	0	12	6

Baseline Characteristics

An Efficacy and Safety Study of Paliperidone Palmitate in Participants With Schizophrenia

Baseline characteristics by cohort

Measure	Placebo (Double-blind) n=164 Participants Matching Placebo was given intramuscularly (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64. Participants who completed double-blind period or discontinued early from double-blind period had follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants did not receive any study drug during post-observational period.	Paliperidone Palmitate (Double-blind) n=159 Participants Paliperidone palmitate was given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64. Participants who completed double-blind period or discontinued early from double-blind period had follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants did not receive any study drug during post-observational period.	Total n=323 Participants Total of all reporting groups
Age Continuous	44.0 years STANDARD_DEVIATION 12.41 • n=5 Participants	45.7 years STANDARD_DEVIATION 13.55 • n=7 Participants	44.8 years STANDARD_DEVIATION 12.99 • n=5 Participants
Sex: Female, Male Female	81 Participants n=5 Participants	58 Participants n=7 Participants	139 Participants n=5 Participants
Sex: Female, Male Male	83 Participants n=5 Participants	101 Participants n=7 Participants	184 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 13 or early discontinuation

Population: Full Analysis Set (FAS) population included all randomly assigned participants who received at least 1 injection of double-blind study drug and had baseline and at least 1 post-baseline PANSS total scores. Last Observation Carried Forward (LOCF) method was used.

The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210, higher scores indicate worsening.

Outcome measures

Measure	Placebo (Double-blind) n=164 Participants Matching Placebo was given intramuscularl (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64.	Paliperidone Palmitate (Double-blind) n=158 Participants Paliperidone palmitate was given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64.
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 13 or Early Discontinuation Baseline	83.5 units on a scale Standard Deviation 15.18	85.7 units on a scale Standard Deviation 14.57
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 13 or Early Discontinuation Change at Week 13 or Early Discontinuation	6.9 units on a scale Standard Deviation 19.13	-3.1 units on a scale Standard Deviation 20.32

SECONDARY outcome

Timeframe: Baseline and Week 13 or early discontinuation

Population: FAS population included all randomly assigned participants who received at least 1 injection of double-blind study drug and had baseline and at least 1 post-baseline PANSS total scores. LOCF method was used.

The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants", higher scores indicate worsening.

Outcome measures

Measure	Placebo (Double-blind) n=164 Participants Matching Placebo was given intramuscularl (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64.	Paliperidone Palmitate (Double-blind) n=158 Participants Paliperidone palmitate was given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64.
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 13 or Early Discontinuation Baseline	4.0 units on a scale Interval 2.0 to 7.0	4.0 units on a scale Interval 2.0 to 6.0
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 13 or Early Discontinuation Change at Week 13 or Early Discontinuation	0.0 units on a scale Interval -3.0 to 3.0	0.0 units on a scale Interval -3.0 to 3.0

SECONDARY outcome

Timeframe: up to Week 13 or early discontinuation

Population: FAS population included all randomly assigned participants who received at least 1 injection of double-blind study drug and had baseline and at least 1 post-baseline PANSS total scores. LOCF method was used.

Participants with response were defined as those participants who shows 30 percent or more and 20 percent or more reduction in PANSS total score.

Outcome measures

Measure	Placebo (Double-blind) n=164 Participants Matching Placebo was given intramuscularl (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64.	Paliperidone Palmitate (Double-blind) n=158 Participants Paliperidone palmitate was given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64.
Participants With Response to the Treatment as Per PANSS Total Score. Greater than or equal to 30 percent Improvement	14 participants	36 participants
Participants With Response to the Treatment as Per PANSS Total Score. Greater than or equal to 20 percent Improvement	23 participants	52 participants

SECONDARY outcome

Timeframe: Baseline and Week 13 or early discontinuation (ED)

Population: FAS population included all randomly assigned participants who received at least 1 injection of double-blind study drug and had baseline and at least 1 post-baseline PANSS total scores. LOCF method was used.

The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). Positive symptoms subscale consists of 8 items with total score range of 8-56; negative symptoms subscale and disorganized thoughts subscale, each consists of 7 items with total score range of 7-49, uncontrolled hostility/excitement subscale and anxiety/depression subscale, each consists of 4 items with total score range of 4-28, higher score indicates greater severity.

Outcome measures

Measure	Placebo (Double-blind) n=164 Participants Matching Placebo was given intramuscularl (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64.	Paliperidone Palmitate (Double-blind) n=158 Participants Paliperidone palmitate was given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64.
Change From Baseline in PANSS Marder Subscale Scores at Week 13 or Early Discontinuation Negative symptoms: Baseline	21.7 units on a scale Standard Deviation 6.22	22.8 units on a scale Standard Deviation 6.04
Change From Baseline in PANSS Marder Subscale Scores at Week 13 or Early Discontinuation Positive symptoms: Baseline	24.3 units on a scale Standard Deviation 5.56	24.2 units on a scale Standard Deviation 5.66
Change From Baseline in PANSS Marder Subscale Scores at Week 13 or Early Discontinuation Positive symptoms: Change at Week 13 or ED	1.6 units on a scale Standard Deviation 6.06	-1.1 units on a scale Standard Deviation 6.29
Change From Baseline in PANSS Marder Subscale Scores at Week 13 or Early Discontinuation Negative symptoms: Change at Week 13 or ED	0.9 units on a scale Standard Deviation 5.82	-1.4 units on a scale Standard Deviation 5.76
Change From Baseline in PANSS Marder Subscale Scores at Week 13 or Early Discontinuation Disorganized thoughts: Baseline	19.6 units on a scale Standard Deviation 5.13	20.8 units on a scale Standard Deviation 4.83
Change From Baseline in PANSS Marder Subscale Scores at Week 13 or Early Discontinuation Disorganized thoughts: Change at Week 13 or ED	1.9 units on a scale Standard Deviation 5.24	-0.6 units on a scale Standard Deviation 5.11
Change From Baseline in PANSS Marder Subscale Scores at Week 13 or Early Discontinuation Uncontrolled hostility/excitement: Baseline	8.3 units on a scale Standard Deviation 3.07	8.6 units on a scale Standard Deviation 3.42
Change From Baseline in PANSS Marder Subscale Scores at Week 13 or Early Discontinuation Uncontrolled hostility: Change at Week 13 or ED	1.9 units on a scale Standard Deviation 4.23	0.4 units on a scale Standard Deviation 4.15
Change From Baseline in PANSS Marder Subscale Scores at Week 13 or Early Discontinuation Anxiety/depression: Baseline	9.5 units on a scale Standard Deviation 3.02	9.4 units on a scale Standard Deviation 3.14
Change From Baseline in PANSS Marder Subscale Scores at Week 13 or Early Discontinuation Anxiety/depression: Change at Week 13 or ED	0.7 units on a scale Standard Deviation 3.27	-0.4 units on a scale Standard Deviation 3.54

SECONDARY outcome

Timeframe: Baseline and Week 13 or early discontinuation

Population: FAS population included all randomly assigned participants who received at least 1 injection of double-blind study drug and had baseline and at least 1 post-baseline PANSS total scores. LOCF method was used.

Negative Syndrome Scale (range 7-49): Sum of scores for items 1-7 in negative subscale: blunted effect, emotional withdrawal, poor rapport, passive apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking, higher scores indicate worsening.

Outcome measures

Measure	Placebo (Double-blind) n=164 Participants Matching Placebo was given intramuscularl (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64.	Paliperidone Palmitate (Double-blind) n=158 Participants Paliperidone palmitate was given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64.
Change From Baseline in PANSS Negative Subscale Score at Week 13 or Early Discontinuation Baseline	22.7 units on a scale Standard Deviation 6.19	24.0 units on a scale Standard Deviation 5.77
Change From Baseline in PANSS Negative Subscale Score at Week 13 or Early Discontinuation Change at Week 13 or Early Discontinuation	0.9 units on a scale Standard Deviation 5.54	-1.5 units on a scale Standard Deviation 5.38

SECONDARY outcome

Timeframe: Baseline and Week 13 or early discontinuation

Population: FAS population included all randomly assigned participants who received at least 1 injection of double-blind study drug and had baseline and at least 1 post-baseline PANSS total scores. LOCF method was used.

Positive Syndrome Scale (range 7-49): Sum of scores for items 1-7 in positive subscale: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility, higher scores indicate worsening.

Outcome measures

Measure	Placebo (Double-blind) n=164 Participants Matching Placebo was given intramuscularl (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64.	Paliperidone Palmitate (Double-blind) n=158 Participants Paliperidone palmitate was given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64.
Change From Baseline in PANSS Positive Subscale Score at Week 13 or Early Discontinuation Baseline	19.3 units on a scale Standard Deviation 4.97	19.5 units on a scale Standard Deviation 5.47
Change From Baseline in PANSS Positive Subscale Score at Week 13 or Early Discontinuation Change at Week 13 or Early Discontinuation	2.2 units on a scale Standard Deviation 5.82	-0.6 units on a scale Standard Deviation 6.19

SECONDARY outcome

Timeframe: Baseline and Week 13 or early discontinuation

Population: FAS population included all randomly assigned participants who received at least 1 injection of double-blind study drug and had baseline and at least 1 post-baseline PANSS total scores. LOCF method was used.

General Psychopathology (range 16-112): Sum of scores for somatic concern, anxiety, guilt feelings, tension, mannerisms/posturing, depression, motor retardation, uncooperativeness, unusual thought content, disoriented, poor attention, lack of judgment/insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance, higher scores indicate worsening.

Outcome measures

Measure	Placebo (Double-blind) n=164 Participants Matching Placebo was given intramuscularl (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64.	Paliperidone Palmitate (Double-blind) n=158 Participants Paliperidone palmitate was given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64.
Change From Baseline in PANSS General Psychopathology Subscale Score at Week 13 or Early Discontinuation Baseline	41.4 units on a scale Standard Deviation 7.97	42.3 units on a scale Standard Deviation 7.85
Change From Baseline in PANSS General Psychopathology Subscale Score at Week 13 or Early Discontinuation Change at Week 13 or Early Discontinuation	3.8 units on a scale Standard Deviation 10.32	-1.0 units on a scale Standard Deviation 11.04

Adverse Events

Placebo (Double-blind)

Serious events: 25 serious events

Other events: 131 other events

Deaths: 0 deaths

Paliperidone Palmitate (Double-blind)

Serious events: 10 serious events

Other events: 133 other events

Deaths: 0 deaths

Placebo (Post-observational)

Serious events: 4 serious events

Other events: 94 other events

Deaths: 0 deaths

Paliperidone Palmitate (Post-0bservational)

Serious events: 6 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo (Double-blind) n=164 participants at risk Matching Placebo was given intramuscularly (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64.	Paliperidone Palmitate (Double-blind) n=159 participants at risk Paliperidone palmitate was given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64.	Placebo (Post-observational) n=156 participants at risk Participants who completed double-blind period or discontinued early from double-blind period had follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants did not receive any study drug during post-observational period.	Paliperidone Palmitate (Post-0bservational) n=155 participants at risk Participants who completed double-blind period or discontinued early from double-blind period had follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants did not receive any study drug during post-observational period.
Metabolism and nutrition disorders Dehydration	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Hyponatraemia	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Psychiatric symptom	7.9% 13/164 • From signing of the informed consent until study completion.	2.5% 4/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Psychiatric disorders Schizophrenia	1.8% 3/164 • From signing of the informed consent until study completion.	2.5% 4/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Psychiatric disorders Suicide attempt	1.2% 2/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Delusion	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Hallucination, auditory	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Psychiatric disorders Mental status changes	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Self injurious behaviour	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Convulsion	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Epilepsy	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Loss of consciousness	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Gastritis	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Hepatobiliary disorders Cholecystitis acute	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Reproductive system and breast disorders Ovarian cyst torsion	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Akathisia	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.

Other adverse events

Measure	Placebo (Double-blind) n=164 participants at risk Matching Placebo was given intramuscularly (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64.	Paliperidone Palmitate (Double-blind) n=159 participants at risk Paliperidone palmitate was given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64.	Placebo (Post-observational) n=156 participants at risk Participants who completed double-blind period or discontinued early from double-blind period had follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants did not receive any study drug during post-observational period.	Paliperidone Palmitate (Post-0bservational) n=155 participants at risk Participants who completed double-blind period or discontinued early from double-blind period had follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants did not receive any study drug during post-observational period.
Injury, poisoning and procedural complications Chillblains	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Fracture	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Laceration	1.8% 3/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Scratch	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Weight fluctuation	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Abnormal behaviour	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Disorientation	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Poor quality sleep	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Gastrointestinal disorder	1.8% 3/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Abdominal distension	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Defaecation urgency	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Haemorrhoids	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Infections and infestations Nasopharyngitis	6.1% 10/164 • From signing of the informed consent until study completion.	12.6% 20/159 • From signing of the informed consent until study completion.	8.3% 13/156 • From signing of the informed consent until study completion.	8.4% 13/155 • From signing of the informed consent until study completion.
Infections and infestations Upper respiratory tract infection	4.3% 7/164 • From signing of the informed consent until study completion.	5.0% 8/159 • From signing of the informed consent until study completion.	2.6% 4/156 • From signing of the informed consent until study completion.	3.9% 6/155 • From signing of the informed consent until study completion.
Infections and infestations Cystitis	0.00% 0/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Infections and infestations Hordeolum	1.2% 2/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Infections and infestations Tinea pedis	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Infections and infestations Urinary tract infection	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	1.9% 3/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Infections and infestations Adenoviral conjunctivitis	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Infections and infestations Rhinitis	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Infections and infestations Vaginal infection	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Blood and lymphatic system disorders Anaemia	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Blood and lymphatic system disorders Leukopenia	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Decreased appetite	3.7% 6/164 • From signing of the informed consent until study completion.	3.1% 5/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Hyperlipidaemia	1.2% 2/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Hypokalaemia	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Dehydration	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Diet refusal	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Hyperphagia	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Hyperuricaemia	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Insomnia	15.2% 25/164 • From signing of the informed consent until study completion.	17.0% 27/159 • From signing of the informed consent until study completion.	3.8% 6/156 • From signing of the informed consent until study completion.	3.9% 6/155 • From signing of the informed consent until study completion.
Psychiatric disorders Psychiatric symptom	20.1% 33/164 • From signing of the informed consent until study completion.	8.8% 14/159 • From signing of the informed consent until study completion.	2.6% 4/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Psychiatric disorders Anxiety	7.9% 13/164 • From signing of the informed consent until study completion.	6.3% 10/159 • From signing of the informed consent until study completion.	3.2% 5/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Psychiatric disorders Aggression	0.61% 1/164 • From signing of the informed consent until study completion.	2.5% 4/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Psychiatric disorders Agitation	2.4% 4/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Hallucination, auditory	1.2% 2/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Delusion	0.61% 1/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Psychiatric disorders Persecutory delusion	1.2% 2/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Psychotic disorder	0.61% 1/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Hallucination	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Sleep disorder	1.2% 2/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Self injurious behaviour	1.2% 2/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Anger	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Catatonia	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Depression	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Psychiatric disorders Emotional disorder	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Hostility	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Inappropriate affect	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Initial insomnia	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Obsessive thoughts	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Restlessness	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Soliloquy	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Somatic delusion	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Impulse-control disorder	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Extrapyramidal disorder	4.9% 8/164 • From signing of the informed consent until study completion.	10.1% 16/159 • From signing of the informed consent until study completion.	3.8% 6/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Nervous system disorders Headache	3.7% 6/164 • From signing of the informed consent until study completion.	5.0% 8/159 • From signing of the informed consent until study completion.	3.2% 5/156 • From signing of the informed consent until study completion.	2.6% 4/155 • From signing of the informed consent until study completion.
Nervous system disorders Akathisia	1.8% 3/164 • From signing of the informed consent until study completion.	5.0% 8/159 • From signing of the informed consent until study completion.	7.1% 11/156 • From signing of the informed consent until study completion.	3.2% 5/155 • From signing of the informed consent until study completion.
Nervous system disorders Dizziness	3.0% 5/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	2.6% 4/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Nervous system disorders Tremor	1.2% 2/164 • From signing of the informed consent until study completion.	2.5% 4/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	1.9% 3/155 • From signing of the informed consent until study completion.
Nervous system disorders Dystonia	0.61% 1/164 • From signing of the informed consent until study completion.	2.5% 4/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Parkinsonism	1.8% 3/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	3.2% 5/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Nervous system disorders Sedation	0.00% 0/164 • From signing of the informed consent until study completion.	1.9% 3/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Nervous system disorders Hypoaesthesia	0.00% 0/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Somnolence	0.00% 0/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	2.6% 4/155 • From signing of the informed consent until study completion.
Nervous system disorders Bradykinesia	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Disturbance in attention	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Drooling	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	1.9% 3/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Nervous system disorders Dyskinesia	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Hypersomnia	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Psychomotor hyperactivity	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Sleep phase rhythm disturbance	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Syncope	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Eye disorders Asthenopia	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Cognitive disorder	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Intracranial haematoma	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Head titubation	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Thermohyperaesthesia	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Eye disorders Eye discharge	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Eye disorders Eye pain	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Eye disorders Eyelid oedema	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Eye disorders Oculogyric crisis	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Eye disorders Ocular discomfort	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Ear and labyrinth disorders Vertigo	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Ear and labyrinth disorders Auricular swelling	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Ear and labyrinth disorders Tinnitus	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Cardiac disorders Bradycardia	1.8% 3/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Cardiac disorders Palpitations	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Cardiac disorders Tachycardia	1.2% 2/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Cardiac disorders Atrial fibrillation	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Cardiac disorders Sinus bradycardia	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Cardiac disorders Ventricular extrasystoles	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Cardiac disorders Left ventricular hypertrophy	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Vascular disorders Hypertension	1.2% 2/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Vascular disorders Orthostatic hypotension	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Vascular disorders Haematoma	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Vascular disorders Hypotension	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Vascular disorders Labile blood pressure	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Vascular disorders Vasculitis	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Vascular disorders Haemorrhage	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Cough	0.61% 1/164 • From signing of the informed consent until study completion.	2.5% 4/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Nasal obstruction	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Productive cough	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Hepatobiliary disorders Liver injury	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Eczema	1.8% 3/164 • From signing of the informed consent until study completion.	2.5% 4/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Periodontitis	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Pruritus	2.4% 4/164 • From signing of the informed consent until study completion.	1.9% 3/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	2.6% 4/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Rash	1.2% 2/164 • From signing of the informed consent until study completion.	1.9% 3/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	1.9% 3/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Acne	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Dermatitis	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Dermatitis atopic	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Hyperkeratosis	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Skin chapped	1.2% 2/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Dermatitis contact	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Eczema nummular	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Erythema	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Skin lesion	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Nail bed inflammation	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Arthralgia	1.2% 2/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	1.9% 3/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Pain in extremity	0.61% 1/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Back pain	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	1.9% 3/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Myalgia	1.2% 2/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Chest pain	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Feeling abnormal	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Hunger	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Weight decreased	4.3% 7/164 • From signing of the informed consent until study completion.	1.9% 3/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Investigations Weight increased	0.00% 0/164 • From signing of the informed consent until study completion.	4.4% 7/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood urine present	1.2% 2/164 • From signing of the informed consent until study completion.	1.9% 3/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Alanine aminotransferase increased	0.61% 1/164 • From signing of the informed consent until study completion.	1.9% 3/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood glucose increased	1.2% 2/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood cholesterol increased	1.2% 2/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Aspartate aminotransferase increased	0.00% 0/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood pressure increased	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood triglycerides increased	1.2% 2/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood urea increased	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Electrocardiogram QT prolonged	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Gamma-glutamyltransferase increased	0.00% 0/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Liver function test abnormal	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Low density lipoprotein increased	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Periorbital haematoma	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Tendon rupture	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Anal injury	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Infections and infestations Bronchitis	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Stomatitis	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Infections and infestations Influenza	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Infections and infestations Pharyngitis	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Infections and infestations Tinea infection	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Infections and infestations Acute tonsillitis	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Infections and infestations Carbuncle	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Infections and infestations Cellulitis	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Infections and infestations Furuncle	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Infections and infestations Gastroenteritis	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Infections and infestations Herpes zoster	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Infections and infestations Impetigo	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Infections and infestations Paronychia	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Infections and infestations Helicobacter infection	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Infections and infestations Acarodermatitis	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Immune system disorders Hypersensitivity	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Increased appetite	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Metabolism and nutrition disorders Polydipsia	0.00% 0/164 • From signing of the informed consent until study completion.	1.9% 3/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Middle insomnia	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Psychiatric disorders Schizophrenia	4.3% 7/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Psychiatric disorders Intentional self-injury	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Suicidal ideation	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Psychiatric disorders Thinking abnormal	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Psychiatric disorders Self-injurious ideation	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Psychiatric disorders Burnout syndrome	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Dysarthria	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Convulsion	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Essential tremor	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Eye disorders Vision blurred	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Eye disorders Conjunctivitis	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Eye disorders Conjunctivitis allergic	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Eye disorders Dry eye	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Ear and labyrinth disorders Ear pain	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Cardiac disorders Diastolic dysfunction	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	1.8% 3/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Rhinitis seasonal	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Constipation	5.5% 9/164 • From signing of the informed consent until study completion.	5.7% 9/159 • From signing of the informed consent until study completion.	8.3% 13/156 • From signing of the informed consent until study completion.	5.2% 8/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Diarrhoea	3.7% 6/164 • From signing of the informed consent until study completion.	3.1% 5/159 • From signing of the informed consent until study completion.	2.6% 4/156 • From signing of the informed consent until study completion.	1.9% 3/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Toothache	2.4% 4/164 • From signing of the informed consent until study completion.	3.1% 5/159 • From signing of the informed consent until study completion.	2.6% 4/156 • From signing of the informed consent until study completion.	1.9% 3/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Abdominal discomfort	3.0% 5/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	2.6% 4/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Abdominal pain upper	0.61% 1/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	3.2% 5/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Nausea	4.9% 8/164 • From signing of the informed consent until study completion.	3.8% 6/159 • From signing of the informed consent until study completion.	2.6% 4/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Dry mouth	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	1.9% 3/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Dyspepsia	1.8% 3/164 • From signing of the informed consent until study completion.	1.9% 3/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Abdominal pain	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Dental caries	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Vomiting	1.8% 3/164 • From signing of the informed consent until study completion.	5.0% 8/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Dysphagia	0.00% 0/164 • From signing of the informed consent until study completion.	1.9% 3/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Gastritis	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Gastritis atrophic	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Gingival bleeding	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Gingivitis	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Ileus	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Mouth ulceration	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Tongue discolouration	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Lip haemorrhage	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Anal haemorrhage	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Tongue haemorrhage	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Hepatobiliary disorders Hepatitis toxic	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Skin and subcutaneous tissue disorders Swelling face	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Muscle rigidity	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Gastrointestinal disorders Epigastric discomfort	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	1.2% 2/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Renal and urinary disorders Dysuria	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	1.9% 3/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Renal and urinary disorders Urinary retention	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Renal and urinary disorders Micturition disorder	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Renal and urinary disorders Renal failure chronic	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Renal and urinary disorders Urge incontinence	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Renal and urinary disorders Urinary incontinence	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Renal and urinary disorders Stress urinary incontinence	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	1.9% 3/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Reproductive system and breast disorders Ejaculation disorder	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Reproductive system and breast disorders Menstruation irregular	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Reproductive system and breast disorders Pruritus genital	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
General disorders Pyrexia	1.8% 3/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	2.6% 4/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
General disorders Malaise	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
General disorders Asthenia	1.2% 2/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
General disorders Fatigue	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Feeling cold	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Injection site pain	6.7% 11/164 • From signing of the informed consent until study completion.	13.2% 21/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Irritability	1.2% 2/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Oedema	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
General disorders Oedema peripheral	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Pain	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood creatine phosphokinase increased	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood prolactin increased	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood lactate dehydrogenase increased	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood potassium increased	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Platelet count decreased	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Investigations Red blood cell count decreased	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Investigations Hepatic enzyme abnormal	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Investigations Influenza A virus test positive	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Contusion	1.8% 3/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Excoriation	2.4% 4/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	1.3% 2/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Fall	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	1.3% 2/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Arthropod sting	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Hepatobiliary disorders Hepatic function abnormal	0.61% 1/164 • From signing of the informed consent until study completion.	3.1% 5/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Torticollis	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Muscle fatigue	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Musculoskeletal and connective tissue disorders Nuchal rigidity	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Renal and urinary disorders Glycosuria	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Renal and urinary disorders Pollakiuria	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Renal and urinary disorders Proteinuria	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Reproductive system and breast disorders Menorrhagia	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Reproductive system and breast disorders Nipple pain	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Injection site induration	2.4% 4/164 • From signing of the informed consent until study completion.	3.8% 6/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Chest discomfort	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Injection site swelling	0.00% 0/164 • From signing of the informed consent until study completion.	2.5% 4/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Gait disturbance	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Injection site haematoma	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Injection site warmth	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Protein urine present	0.00% 0/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
General disorders Vessel puncture site swelling	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Urobilinogen urine increased	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood bicarbonate decreased	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood bilirubin increased	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood chloride increased	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood creatinine increased	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood pressure decreased	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood sodium decreased	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Glucose urine present	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Glycosylated haemoglobin increased	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Neutrophil count increased	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations White blood cell count decreased	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Surgical and medical procedures Tooth extraction	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Superficial injury of eye	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Wound	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Lip injury	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations White blood cell count increased	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Blood phosphorus decreased	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Investigations Lymphocyte percentage decreased	0.00% 0/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Head injury	1.2% 2/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/164 • From signing of the informed consent until study completion.	1.3% 2/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Injury, poisoning and procedural complications Subcutaneous haematoma	0.61% 1/164 • From signing of the informed consent until study completion.	0.63% 1/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.
Nervous system disorders Tardive dyskinesia	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.64% 1/156 • From signing of the informed consent until study completion.	0.65% 1/155 • From signing of the informed consent until study completion.
Nervous system disorders Dysstasia	0.61% 1/164 • From signing of the informed consent until study completion.	0.00% 0/159 • From signing of the informed consent until study completion.	0.00% 0/156 • From signing of the informed consent until study completion.	0.00% 0/155 • From signing of the informed consent until study completion.

Additional Information

Medical director

Janssen Pharmaceutical K.K

Phone: +81-3-4411-5509

Results disclosure agreements

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