Trial Outcomes & Findings for Study Evaluating Long-Term Safety of Desvenlafaxine Succinate Sustained Release With Japanese Adult Subjects in Major Depressive Disorder (MDD) (NCT NCT00831415)

Last Updated: 2018-12-07

Results Overview

HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4) with 0=none/absent and 4=most severe, for a maximum total score of 50. Higher scores indicate greater severity. FOT evaluation is defined as the last "on-therapy" evaluation, regardless of the number of days on therapy. Analysis on Observed cases (non-missing data) and Last observation carried forward (LOCF); LOCF method of imputation for any missing value at any visit.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

304 participants

Primary outcome timeframe

Baseline (Extension Study) up to Day 308 or Final On-Therapy (FOT) Evaluation

Results posted on

2018-12-07

Participant Flow

This was a 10-month, open-label, multicenter study of Japanese participants with Major Depressive Disorder (MDD) conducted from March 2009 to March 2011 at 61 sites in Japan.

A total of 304 participants who completed the short-term Core Study (NCT00798707 \[3151A1-3359 / B2061003\]) consented to enroll in this long-term, open-label, flexible dosing Extension study (NCT00831415 \[3151A1-3350 / B2061002\]). Baseline in this Extension study = Day 56 of the Core study.

Participant milestones

Participant milestones
Measure	DVS SR Desvenlafaxine succinate sustained release formulation (DVS SR) flexible dose 25 milligrams per day (mg/day) up to 100 mg/day.
Overall Study STARTED	304
Overall Study Completers for "Exposure"	227
Overall Study Study "Completers"	227
Overall Study COMPLETED	229
Overall Study NOT COMPLETED	75

Reasons for withdrawal

Reasons for withdrawal
Measure	DVS SR Desvenlafaxine succinate sustained release formulation (DVS SR) flexible dose 25 milligrams per day (mg/day) up to 100 mg/day.
Overall Study Adverse Event	14
Overall Study Failed to return	3
Overall Study Physician Decision	6
Overall Study Lost to Follow-up	9
Overall Study Protocol Violation	3
Overall Study Withdrawal by Subject	35
Overall Study Unsatisfactory response - Efficacy	4
Overall Study Death	1

Baseline Characteristics

Study Evaluating Long-Term Safety of Desvenlafaxine Succinate Sustained Release With Japanese Adult Subjects in Major Depressive Disorder (MDD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DVS SR n=304 Participants DVS SR flexible dose 25 mg/day up to 100 mg/day.
Age, Continuous	38.45 years STANDARD_DEVIATION 10.81 • n=5 Participants
Sex: Female, Male Female	149 Participants n=5 Participants
Sex: Female, Male Male	155 Participants n=5 Participants
Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) score	12.86 scores on a scale STANDARD_DEVIATION 6.30 • n=5 Participants
Categorical scores on Clinical Global Impression-Improvement [CGI-I] 1=Very much improved	75 participants n=5 Participants
Categorical scores on Clinical Global Impression-Improvement [CGI-I] 2=Much improved	81 participants n=5 Participants
Categorical scores on Clinical Global Impression-Improvement [CGI-I] 3=Minimally improved	94 participants n=5 Participants
Categorical scores on Clinical Global Impression-Improvement [CGI-I] 4=No change	51 participants n=5 Participants
Categorical scores on Clinical Global Impression-Improvement [CGI-I] 5=Minimally worse	3 participants n=5 Participants
Clinical Global Impression-Severity of Illness [CGI-S] score	3.25 scores on a scale STANDARD_DEVIATION 1.11 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Extension Study) up to Day 308 or Final On-Therapy (FOT) Evaluation

Population: Intent to treat (ITT): all enrolled participants who received at least 1 dose of study treatment in Extension Study and at least 1 available post-baseline evaluation for any endpoint; (n)=number of participants with analyzable data at observation.

Outcome measures

Outcome measures
Measure	DVS SR n=304 Participants DVS SR flexible dose 25 mg/day up to 100 mg/day.
Change From Baseline in Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) Score LOCF - change at FOT (n=304)	-4.76 scores on a scale Interval -5.47 to -4.05
Change From Baseline in Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) Score Observed cases - change at Day 308 (n=224)	-5.82 scores on a scale Interval -6.61 to -5.03

PRIMARY outcome

Timeframe: Baseline (Extension Study) up to Day 329 or 15 days after last dose of study treatment

Population: Safety population: all enrolled participants who received at least 1 dose of study treatment in this extension study.

Any untoward medical occurrence in a participant who received study treatment was considered an AE without regard to possibility of causal relationship. An AE resulting in any of the following outcomes, or deemed to be significant for any other reason, was considered to be an SAE: death; initial or prolonged inpatient hospitalization; a life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly.

Outcome measures

Outcome measures
Measure	DVS SR n=304 Participants DVS SR flexible dose 25 mg/day up to 100 mg/day.
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) Adverse Events	81.3 percentage of participants
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) Serious Adverse Events	2.6 percentage of participants

SECONDARY outcome

Timeframe: Day 308 or FOT Evaluation

Population: ITT; LOCF. Improvement measured against CGI-I baseline (Day -1) data in Core study (NCT00798707 \[3151A1-3359 / B2061003\]).

CGI-I is a 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.

Outcome measures

Outcome measures
Measure	DVS SR n=304 Participants DVS SR flexible dose 25 mg/day up to 100 mg/day.
Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) 6=Much worse	1 participants
Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) 1=Very much improved	164 participants
Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) 2=Much improved	82 participants
Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) 3=Minimally improved	36 participants
Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) 4=No change	15 participants
Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) 5=Minimally worse	6 participants
Number of Participants With Categorical Scores on Clinical Global Impression-Improvement (CGI-I) 7=Very much worse	0 participants

SECONDARY outcome

Timeframe: Baseline (Extension Study) up to Day 308 or FOT Evaluation

Population: ITT; LOCF and Observed cases (non-missing data); (n)=number of participants with analyzable data at observation.

CGI-S is a 7-point clinician rated scale to assess severity of current illness state. Range is 1 (normal - not ill at all) to 7 (among the most extremely ill). Higher score = more affected.

Outcome measures

Outcome measures
Measure	DVS SR n=304 Participants DVS SR flexible dose 25 mg/day up to 100 mg/day.
Change From Baseline in Clinical Global Impression-Severity of Illness [CGI-S] Score LOCF - change at FOT (n=304)	-0.82 scores on a scale Interval -0.94 to -0.7
Change From Baseline in Clinical Global Impression-Severity of Illness [CGI-S] Score Observed cases - change at Day 308 (n=224)	-0.95 scores on a scale Interval -1.09 to -0.8

Adverse Events

DVS SR

Serious events: 8 serious events

Other events: 247 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DVS SR n=304 participants at risk DVS SR flexible dose 25 mg/day up to 100 mg/day.
Infections and infestations Gastroenteritis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Infectious mononucleosis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Contusion	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Diabetes mellitus	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large intestine carcinoma	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Completed suicide	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Other adverse events
Measure	DVS SR n=304 participants at risk DVS SR flexible dose 25 mg/day up to 100 mg/day.
Skin and subcutaneous tissue disorders Vitiligo	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Xeroderma	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Social circumstances Pregnancy of partner	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hot flush	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypertension	1.3% 4/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypotension	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Orthostatic hypotension	1.3% 4/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Anaemia	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Iron deficiency anaemia	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Leukopenia	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Lymphadenitis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Lymphadenopathy	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Neutropenia	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrioventricular block first degree	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Palpitations	2.0% 6/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Ventricular extrasystoles	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Ear pain	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Meniere's disease	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Motion sickness	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Tinnitus	3.9% 12/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Vertigo	1.6% 5/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Blepharospasm	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Cataract	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Conjunctivitis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Conjunctivitis allergic	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye pain	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Lacrimation increased	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Retinal vein occlusion	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vision blurred	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vitreous floaters	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal discomfort	3.3% 10/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal distension	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	2.0% 6/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain lower	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	6.6% 20/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Aphthous stomatitis	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Cheilitis	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	5.6% 17/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dental caries	3.0% 9/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	9.5% 29/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dry mouth	2.0% 6/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dyspepsia	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Enterocolitis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Flatulence	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Food poisoning	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastritis	2.0% 6/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal disorder	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal sounds abnormal	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Glossitis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Haemorrhoids	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Irritable bowel syndrome	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	12.5% 38/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Oral discomfort	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Oral pain	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Stomatitis	2.0% 6/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Toothache	1.3% 4/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	2.6% 8/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chills	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Condition aggravated	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Device dislocation	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Drug withdrawal syndrome	2.3% 7/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Eye complication associated with device	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	1.3% 4/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Feeling abnormal	2.0% 6/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Feeling hot	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Hangover	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Irritability	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Malaise	2.6% 8/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	1.3% 4/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Thirst	3.3% 10/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Gallbladder polyp	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic function abnormal	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic steatosis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Immune system disorders Allergy to arthropod sting	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Immune system disorders Drug hypersensitivity	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Immune system disorders Seasonal allergy	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Acute sinusitis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Adenoviral conjunctivitis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Body tinea	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchitis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Cystitis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Enteritis infectious	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Gastroenteritis	3.0% 9/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Gastroenteritis viral	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Helicobacter infection	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Herpangina	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Herpes simplex	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Herpes virus infection	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Herpes zoster	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Hordeolum	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Influenza	2.3% 7/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Laryngitis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	40.1% 122/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Oral herpes	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Otitis externa	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Otitis media	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Paronychia	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Parotitis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Periodontal infection	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pharyngitis	1.6% 5/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Rhinitis	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Tinea infection	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Tinea pedis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Tonsillitis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Arthropod bite	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Arthropod sting	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Bone fissure	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Chillblains	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Contusion	3.0% 9/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Excoriation	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fall	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Head injury	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Heat illness	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Heat stroke	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Injury corneal	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Intentional overdose	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Joint sprain	1.3% 4/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Laceration	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Meniscus lesion	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Mouth injury	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Muscle strain	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Road traffic accident	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Thermal burn	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Whiplash injury	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Alanine aminotransferase increased	3.0% 9/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Aspartate aminotransferase increased	1.6% 5/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood alkaline phosphatase increased	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood bilirubin increased	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood creatine phosphokinase increased	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood glucose increased	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood potassium decreased	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood pressure diastolic increased	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood pressure increased	2.0% 6/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood prolactin increased	2.3% 7/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood triglycerides increased	2.3% 7/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood uric acid increased	1.3% 4/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood urine present	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Electrocardiogram QT prolonged	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Gamma-glutamyltransferase increased	2.6% 8/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Glucose urine present	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Haematocrit decreased	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Haemoglobin decreased	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Lipids abnormal	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Lipids increased	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Liver function test abnormal	2.0% 6/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Neutrophil count decreased	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Occult blood positive	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Platelet count decreased	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Protein urine present	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Red blood cell count decreased	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Urine ketone body present	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Weight decreased	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Weight increased	6.2% 19/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations White blood cell count decreased	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations White blood cell count increased	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Decreased appetite	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyperlipidaemia	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyperphagia	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Increased appetite	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	2.0% 6/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	5.6% 17/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Joint stiffness	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Muscle spasms	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Muscle tightness	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Muscular weakness	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	2.6% 8/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Myalgia	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Neck pain	1.3% 4/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in jaw	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Periarthritis	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Scoliosis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Temporomandibular joint syndrome	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Trigger finger	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of liver	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Autonomic nervous system imbalance	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	11.8% 36/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness postural	3.3% 10/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dysgeusia	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	11.8% 36/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Hypoaesthesia	2.0% 6/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Intercostal neuralgia	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Irregular sleep phase	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Memory impairment	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Migraine	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Paraesthesia	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Sedation	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Somnolence	12.5% 38/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Tremor	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Visual field defect	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Anger	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Anxiety	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression	4.6% 14/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression suicidal	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Dissociative disorder	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Eating disorder	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Hallucination	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Impulsive behaviour	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Initial insomnia	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Insomnia	4.3% 13/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Insomnia related to another mental condition	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Intentional self-injury	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Libido decreased	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Nervousness	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Nightmare	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Restlessness	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Self injurious behaviour	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Suicidal ideation	3.9% 12/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Withdrawal syndrome	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Calculus ureteric	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Pollakiuria	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Proteinuria	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Dysmenorrhoea	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Endometriosis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Erectile dysfunction	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Genital haemorrhage	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Menstrual disorder	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Menstruation delayed	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Menstruation irregular	1.6% 5/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Metrorrhagia	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Oligomenorrhoea	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Premenstrual syndrome	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Sexual dysfunction	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Vaginal haemorrhage	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Asthma	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Hiccups	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Hyperventilation	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.6% 5/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Suffocation feeling	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Yawning	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Alopecia areata	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Dermatitis contact	1.3% 4/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Dry skin	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Eczema	1.6% 5/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Heat rash	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.3% 4/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Hyperkeratosis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Night sweats	0.66% 2/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Pruritus	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Psoriasis	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash generalised	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Skin odour abnormal	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Toxic skin eruption	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Urticaria	0.99% 3/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Urticaria thermal	0.33% 1/304 • Events were collected from the time of the signing of the informed consent form up to 15 days after the last dose of study treatment was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER