1
Introduction
1.1
Tutorial: Subject-level visualizations and tables
1.1.1
Scatter plots and spaghetti plots
1.1.2
Linked tables
1.2
Tutorial: Summarized visualizations and tables
1.2.1
Summary plots
1.2.2
Summary tables
2
Patient profiles
3
Alerts
3.1
Death
4
Subject disposition
4.1
Enrollment by country and site
4.1.1
Treemap visualization
4.2
Cumulative enrollment by date
4.3
Randomized patients by visit
4.4
Discontinuation table
4.5
Discontinuation listing: comparison
4.6
Demographics
5
Adverse events
5.1
Adverse events summary
5.2
Adverse events summary: comparison
5.3
Adverse events counts
5.3.1
Treemap visualization
5.3.2
Sunburst visualization
5.4
Adverse events listing: comparison
5.5
Treatment-emergent adverse events time intervals
5.5.1
CARDIAC DISORDERS
5.5.1.1
ATRIAL FIBRILLATION
5.5.1.2
ATRIAL FLUTTER
5.5.1.3
ATRIAL HYPERTROPHY
5.5.1.4
ATRIOVENTRICULAR BLOCK FIRST DEGREE
5.5.1.5
ATRIOVENTRICULAR BLOCK SECOND DEGREE
5.5.1.6
BRADYCARDIA
5.5.1.7
BUNDLE BRANCH BLOCK LEFT
5.5.1.8
BUNDLE BRANCH BLOCK RIGHT
5.5.1.9
CARDIAC DISORDER
5.5.1.10
CARDIAC FAILURE CONGESTIVE
5.5.1.11
MYOCARDIAL INFARCTION
5.5.1.12
PALPITATIONS
5.5.1.13
SINUS ARRHYTHMIA
5.5.1.14
SINUS BRADYCARDIA
5.5.1.15
SUPRAVENTRICULAR EXTRASYSTOLES
5.5.1.16
SUPRAVENTRICULAR TACHYCARDIA
5.5.1.17
TACHYCARDIA
5.5.1.18
VENTRICULAR EXTRASYSTOLES
5.5.1.19
VENTRICULAR HYPERTROPHY
5.5.1.20
WOLFF-PARKINSON-WHITE SYNDROME
5.5.2
CONGENITAL, FAMILIAL AND GENETIC DISORDERS
5.5.2.1
VENTRICULAR SEPTAL DEFECT
5.5.3
EAR AND LABYRINTH DISORDERS
5.5.3.1
CERUMEN IMPACTION
5.5.3.2
EAR PAIN
5.5.3.3
VERTIGO
5.5.4
EYE DISORDERS
5.5.4.1
CONJUNCTIVAL HAEMORRHAGE
5.5.4.2
CONJUNCTIVITIS
5.5.4.3
EYE ALLERGY
5.5.4.4
EYE PRURITUS
5.5.4.5
EYE SWELLING
5.5.4.6
VISION BLURRED
5.5.5
GASTROINTESTINAL DISORDERS
5.5.5.1
ABDOMINAL DISCOMFORT
5.5.5.2
ABDOMINAL PAIN
5.5.5.3
CONSTIPATION
5.5.5.4
DIARRHOEA
5.5.5.5
DYSPEPSIA
5.5.5.6
DYSPHAGIA
5.5.5.7
FLATULENCE
5.5.5.8
GASTROINTESTINAL HAEMORRHAGE
5.5.5.9
GASTROOESOPHAGEAL REFLUX DISEASE
5.5.5.10
GLOSSITIS
5.5.5.11
HIATUS HERNIA
5.5.5.12
NAUSEA
5.5.5.13
RECTAL HAEMORRHAGE
5.5.5.14
SALIVARY HYPERSECRETION
5.5.5.15
STOMACH DISCOMFORT
5.5.5.16
VOMITING
5.5.6
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
5.5.6.1
APPLICATION SITE BLEEDING
5.5.6.2
APPLICATION SITE DERMATITIS
5.5.6.3
APPLICATION SITE DESQUAMATION
5.5.6.4
APPLICATION SITE DISCHARGE
5.5.6.5
APPLICATION SITE DISCOLOURATION
5.5.6.6
APPLICATION SITE ERYTHEMA
5.5.6.7
APPLICATION SITE INDURATION
5.5.6.8
APPLICATION SITE IRRITATION
5.5.6.9
APPLICATION SITE PAIN
5.5.6.10
APPLICATION SITE PERSPIRATION
5.5.6.11
APPLICATION SITE PRURITUS
5.5.6.12
APPLICATION SITE REACTION
5.5.6.13
APPLICATION SITE SWELLING
5.5.6.14
APPLICATION SITE URTICARIA
5.5.6.15
APPLICATION SITE VESICLES
5.5.6.16
APPLICATION SITE WARMTH
5.5.6.17
ASTHENIA
5.5.6.18
CHEST DISCOMFORT
5.5.6.19
CHEST PAIN
5.5.6.20
CHILLS
5.5.6.21
FATIGUE
5.5.6.22
FEELING ABNORMAL
5.5.6.23
FEELING COLD
5.5.6.24
INFLAMMATION
5.5.6.25
MALAISE
5.5.6.26
OEDEMA
5.5.6.27
OEDEMA PERIPHERAL
5.5.6.28
PAIN
5.5.6.29
PYREXIA
5.5.6.30
SECRETION DISCHARGE
5.5.6.31
SUDDEN DEATH
5.5.6.32
SWELLING
5.5.6.33
ULCER
5.5.7
HEPATOBILIARY DISORDERS
5.5.7.1
HYPERBILIRUBINAEMIA
5.5.8
IMMUNE SYSTEM DISORDERS
5.5.8.1
HYPERSENSITIVITY
5.5.9
INFECTIONS AND INFESTATIONS
5.5.9.1
BRONCHITIS
5.5.9.2
CELLULITIS
5.5.9.3
CERVICITIS
5.5.9.4
CYSTITIS
5.5.9.5
EAR INFECTION
5.5.9.6
GASTROENTERITIS VIRAL
5.5.9.7
INFLUENZA
5.5.9.8
LOCALISED INFECTION
5.5.9.9
LOWER RESPIRATORY TRACT INFECTION
5.5.9.10
NASOPHARYNGITIS
5.5.9.11
PNEUMONIA
5.5.9.12
RHINITIS
5.5.9.13
UPPER RESPIRATORY TRACT INFECTION
5.5.9.14
URINARY TRACT INFECTION
5.5.9.15
VAGINAL MYCOSIS
5.5.9.16
VIRAL INFECTION
5.5.10
INJURY, POISONING AND PROCEDURAL COMPLICATIONS
5.5.10.1
CONTUSION
5.5.10.2
EXCORIATION
5.5.10.3
FACIAL BONES FRACTURE
5.5.10.4
FALL
5.5.10.5
HIP FRACTURE
5.5.10.6
JOINT DISLOCATION
5.5.10.7
SKIN LACERATION
5.5.10.8
WOUND
5.5.11
INVESTIGATIONS
5.5.11.1
BIOPSY
5.5.11.2
BIOPSY PROSTATE
5.5.11.3
BLOOD ALKALINE PHOSPHATASE INCREASED
5.5.11.4
BLOOD CHOLESTEROL INCREASED
5.5.11.5
BLOOD CREATINE PHOSPHOKINASE INCREASED
5.5.11.6
BLOOD GLUCOSE INCREASED
5.5.11.7
BLOOD URINE PRESENT
5.5.11.8
BODY TEMPERATURE INCREASED
5.5.11.9
CYSTOSCOPY
5.5.11.10
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION
5.5.11.11
ELECTROCARDIOGRAM T WAVE AMPLITUDE DECREASED
5.5.11.12
ELECTROCARDIOGRAM T WAVE INVERSION
5.5.11.13
HEART RATE INCREASED
5.5.11.14
HEART RATE IRREGULAR
5.5.11.15
NASAL MUCOSA BIOPSY
5.5.11.16
WEIGHT DECREASED
5.5.12
METABOLISM AND NUTRITION DISORDERS
5.5.12.1
DECREASED APPETITE
5.5.12.2
DEHYDRATION
5.5.12.3
DIABETES MELLITUS
5.5.12.4
FOOD CRAVING
5.5.12.5
HYPONATRAEMIA
5.5.12.6
INCREASED APPETITE
5.5.13
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
5.5.13.1
ARTHRALGIA
5.5.13.2
ARTHRITIS
5.5.13.3
BACK PAIN
5.5.13.4
FLANK PAIN
5.5.13.5
MUSCLE SPASMS
5.5.13.6
MUSCULAR WEAKNESS
5.5.13.7
MYALGIA
5.5.13.8
PAIN IN EXTREMITY
5.5.13.9
SHOULDER PAIN
5.5.14
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)
5.5.14.1
COLON CANCER
5.5.14.2
MALIGNANT FIBROUS HISTIOCYTOMA
5.5.14.3
PROSTATE CANCER
5.5.15
NERVOUS SYSTEM DISORDERS
5.5.15.1
AMNESIA
5.5.15.2
BALANCE DISORDER
5.5.15.3
BURNING SENSATION
5.5.15.4
COGNITIVE DISORDER
5.5.15.5
COMPLEX PARTIAL SEIZURES
5.5.15.6
COORDINATION ABNORMAL
5.5.15.7
DIZZINESS
5.5.15.8
HEADACHE
5.5.15.9
HEMIANOPIA HOMONYMOUS
5.5.15.10
HYPERSOMNIA
5.5.15.11
LETHARGY
5.5.15.12
PARAESTHESIA
5.5.15.13
PARAESTHESIA ORAL
5.5.15.14
PARKINSON’S DISEASE
5.5.15.15
PAROSMIA
5.5.15.16
PARTIAL SEIZURES WITH SECONDARY GENERALISATION
5.5.15.17
PSYCHOMOTOR HYPERACTIVITY
5.5.15.18
SOMNOLENCE
5.5.15.19
STUPOR
5.5.15.20
SYNCOPE
5.5.15.21
SYNCOPE VASOVAGAL
5.5.15.22
TRANSIENT ISCHAEMIC ATTACK
5.5.16
PSYCHIATRIC DISORDERS
5.5.16.1
AGITATION
5.5.16.2
ANXIETY
5.5.16.3
COMPLETED SUICIDE
5.5.16.4
CONFUSIONAL STATE
5.5.16.5
DELIRIUM
5.5.16.6
DELUSION
5.5.16.7
DEPRESSED MOOD
5.5.16.8
DISORIENTATION
5.5.16.9
HALLUCINATION
5.5.16.10
HALLUCINATION, VISUAL
5.5.16.11
INSOMNIA
5.5.16.12
IRRITABILITY
5.5.16.13
LIBIDO DECREASED
5.5.16.14
LISTLESS
5.5.16.15
NIGHTMARE
5.5.16.16
RESTLESSNESS
5.5.17
RENAL AND URINARY DISORDERS
5.5.17.1
CALCULUS URETHRAL
5.5.17.2
DYSURIA
5.5.17.3
INCONTINENCE
5.5.17.4
MICTURITION URGENCY
5.5.17.5
NEPHROLITHIASIS
5.5.17.6
POLLAKIURIA
5.5.18
REPRODUCTIVE SYSTEM AND BREAST DISORDERS
5.5.18.1
BENIGN PROSTATIC HYPERPLASIA
5.5.18.2
PELVIC PAIN
5.5.19
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
5.5.19.1
ALLERGIC GRANULOMATOUS ANGIITIS
5.5.19.2
COUGH
5.5.19.3
DYSPHONIA
5.5.19.4
DYSPNOEA
5.5.19.5
EMPHYSEMA
5.5.19.6
EPISTAXIS
5.5.19.7
HAEMOPTYSIS
5.5.19.8
NASAL CONGESTION
5.5.19.9
PHARYNGEAL ERYTHEMA
5.5.19.10
PHARYNGOLARYNGEAL PAIN
5.5.19.11
POSTNASAL DRIP
5.5.19.12
PRODUCTIVE COUGH
5.5.19.13
RALES
5.5.19.14
RESPIRATORY TRACT CONGESTION
5.5.19.15
RHINORRHOEA
5.5.20
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
5.5.20.1
ACTINIC KERATOSIS
5.5.20.2
ALOPECIA
5.5.20.3
BLISTER
5.5.20.4
COLD SWEAT
5.5.20.5
DERMATITIS CONTACT
5.5.20.6
DRUG ERUPTION
5.5.20.7
ERYTHEMA
5.5.20.8
HYPERHIDROSIS
5.5.20.9
PRURITUS
5.5.20.10
PRURITUS GENERALISED
5.5.20.11
RASH
5.5.20.12
RASH ERYTHEMATOUS
5.5.20.13
RASH MACULO-PAPULAR
5.5.20.14
RASH PRURITIC
5.5.20.15
SKIN EXFOLIATION
5.5.20.16
SKIN IRRITATION
5.5.20.17
SKIN ODOUR ABNORMAL
5.5.20.18
SKIN ULCER
5.5.20.19
URTICARIA
5.5.21
SOCIAL CIRCUMSTANCES
5.5.21.1
ALCOHOL USE
5.5.22
SURGICAL AND MEDICAL PROCEDURES
5.5.22.1
ACROCHORDON EXCISION
5.5.22.2
CATARACT OPERATION
5.5.22.3
EYE LASER SURGERY
5.5.22.4
SKIN LESION EXCISION
5.5.23
VASCULAR DISORDERS
5.5.23.1
HOT FLUSH
5.5.23.2
HYPERTENSION
5.5.23.3
HYPOTENSION
5.5.23.4
ORTHOSTATIC HYPOTENSION
5.5.23.5
WOUND HAEMORRHAGE
6
Concomitant medications
6.1
Concomitant medications listing
7
Laboratory
7.1
Laboratory abnormalities summary
7.2
Hepatoxicity (eDISH)
7.3
Laboratory profiles
7.3.1
CHEMISTRY
7.3.1.1
Alanine Aminotransferase (U/L)
7.3.1.2
Albumin (g/L)
7.3.1.3
Alkaline Phosphatase (U/L)
7.3.1.4
Aspartate Aminotransferase (U/L)
7.3.1.5
Bilirubin (umol/L)
7.3.1.6
Blood Urea Nitrogen (mmol/L)
7.3.1.7
Calcium (mmol/L)
7.3.1.8
Chloride (mmol/L)
7.3.1.9
Cholesterol (mmol/L)
7.3.1.10
Creatine Kinase (U/L)
7.3.1.11
Creatinine (umol/L)
7.3.1.12
Gamma Glutamyl Transferase (U/L)
7.3.1.13
Glucose (mmol/L)
7.3.1.14
Phosphate (mmol/L)
7.3.1.15
Potassium (mmol/L)
7.3.1.16
Protein (g/L)
7.3.1.17
Sodium (mmol/L)
7.3.1.18
Urate (umol/L)
7.3.2
HEMATOLOGY
7.3.2.1
Anisocytes ()
7.3.2.2
Basophils (GI/L)
7.3.2.3
Eosinophils (GI/L)
7.3.2.4
Ery Mean Corpuscular Hemoglobin (fmol(Fe))
7.3.2.5
Ery Mean Corpuscular HGB Concentration (mmol/L)
7.3.2.6
Ery Mean Corpuscular Volume (fL)
7.3.2.7
Erythrocytes (TI/L)
7.3.2.8
Hematocrit (1)
7.3.2.9
Hemoglobin (mmol/L)
7.3.2.10
Leukocytes (GI/L)
7.3.2.11
Lymphocytes (GI/L)
7.3.2.12
Macrocytes ()
7.3.2.13
Microcytes ()
7.3.2.14
Monocytes (GI/L)
7.3.2.15
Platelet (GI/L)
7.3.2.16
Poikilocytes ()
7.3.2.17
Polychromasia ()
7.3.3
Not Coded
7.3.3.1
Hemoglobin A1C (1)
7.3.4
OTHER
7.3.4.1
Thyrotropin (mU/L)
7.3.4.2
Vitamin B12 (pmol/L)
7.3.5
URINALYSIS
7.3.5.1
Ketones ()
7.3.5.2
pH ()
7.3.5.3
Specific Gravity ()
7.3.5.4
Urobilinogen ()
7.4
Laboratory profiles by visit
7.4.1
CHEMISTRY
7.4.1.1
Alanine Aminotransferase (U/L)
7.4.1.2
Albumin (g/L)
7.4.1.3
Alkaline Phosphatase (U/L)
7.4.1.4
Aspartate Aminotransferase (U/L)
7.4.1.5
Bilirubin (umol/L)
7.4.1.6
Blood Urea Nitrogen (mmol/L)
7.4.1.7
Calcium (mmol/L)
7.4.1.8
Chloride (mmol/L)
7.4.1.9
Cholesterol (mmol/L)
7.4.1.10
Creatine Kinase (U/L)
7.4.1.11
Creatinine (umol/L)
7.4.1.12
Gamma Glutamyl Transferase (U/L)
7.4.1.13
Glucose (mmol/L)
7.4.1.14
Phosphate (mmol/L)
7.4.1.15
Potassium (mmol/L)
7.4.1.16
Protein (g/L)
7.4.1.17
Sodium (mmol/L)
7.4.1.18
Urate (umol/L)
7.4.2
HEMATOLOGY
7.4.2.1
Anisocytes ()
7.4.2.2
Basophils (GI/L)
7.4.2.3
Eosinophils (GI/L)
7.4.2.4
Ery Mean Corpuscular Hemoglobin (fmol(Fe))
7.4.2.5
Ery Mean Corpuscular HGB Concentration (mmol/L)
7.4.2.6
Ery Mean Corpuscular Volume (fL)
7.4.2.7
Erythrocytes (TI/L)
7.4.2.8
Hematocrit (1)
7.4.2.9
Hemoglobin (mmol/L)
7.4.2.10
Leukocytes (GI/L)
7.4.2.11
Lymphocytes (GI/L)
7.4.2.12
Macrocytes ()
7.4.2.13
Microcytes ()
7.4.2.14
Monocytes (GI/L)
7.4.2.15
Platelet (GI/L)
7.4.2.16
Poikilocytes ()
7.4.2.17
Polychromasia ()
7.4.3
Not Coded
7.4.3.1
Hemoglobin A1C (1)
7.4.4
OTHER
7.4.4.1
Thyrotropin (mU/L)
7.4.4.2
Vitamin B12 (pmol/L)
7.4.5
URINALYSIS
7.4.5.1
Ketones ()
7.4.5.2
pH ()
7.4.5.3
Specific Gravity ()
7.4.5.4
Urobilinogen ()
7.5
Laboratory shift plots
7.5.1
CHEMISTRY
7.5.1.1
Alanine Aminotransferase (U/L)
7.5.1.2
Albumin (g/L)
7.5.1.3
Alkaline Phosphatase (U/L)
7.5.1.4
Aspartate Aminotransferase (U/L)
7.5.1.5
Bilirubin (umol/L)
7.5.1.6
Blood Urea Nitrogen (mmol/L)
7.5.1.7
Calcium (mmol/L)
7.5.1.8
Chloride (mmol/L)
7.5.1.9
Cholesterol (mmol/L)
7.5.1.10
Creatine Kinase (U/L)
7.5.1.11
Creatinine (umol/L)
7.5.1.12
Gamma Glutamyl Transferase (U/L)
7.5.1.13
Glucose (mmol/L)
7.5.1.14
Phosphate (mmol/L)
7.5.1.15
Potassium (mmol/L)
7.5.1.16
Protein (g/L)
7.5.1.17
Sodium (mmol/L)
7.5.1.18
Urate (umol/L)
7.5.2
HEMATOLOGY
7.5.2.1
Anisocytes ()
7.5.2.2
Basophils (GI/L)
7.5.2.3
Eosinophils (GI/L)
7.5.2.4
Ery Mean Corpuscular Hemoglobin (fmol(Fe))
7.5.2.5
Ery Mean Corpuscular HGB Concentration (mmol/L)
7.5.2.6
Ery Mean Corpuscular Volume (fL)
7.5.2.7
Erythrocytes (TI/L)
7.5.2.8
Hematocrit (1)
7.5.2.9
Hemoglobin (mmol/L)
7.5.2.10
Leukocytes (GI/L)
7.5.2.11
Lymphocytes (GI/L)
7.5.2.12
Macrocytes ()
7.5.2.13
Monocytes (GI/L)
7.5.2.14
Platelet (GI/L)
7.5.2.15
Polychromasia ()
7.5.3
Not Coded
7.5.3.1
Hemoglobin A1C (1)
7.5.4
OTHER
7.5.4.1
Thyrotropin (mU/L)
7.5.4.2
Vitamin B12 (pmol/L)
7.5.5
URINALYSIS
7.5.5.1
Ketones ()
7.5.5.2
pH ()
7.5.5.3
Specific Gravity ()
7.5.5.4
Urobilinogen ()
7.6
Laboratory aggregate profiles
7.6.1
CHEMISTRY
7.6.1.1
Alanine Aminotransferase (U/L)
7.6.1.2
Albumin (g/L)
7.6.1.3
Alkaline Phosphatase (U/L)
7.6.1.4
Aspartate Aminotransferase (U/L)
7.6.1.5
Bilirubin (umol/L)
7.6.1.6
Blood Urea Nitrogen (mmol/L)
7.6.1.7
Calcium (mmol/L)
7.6.1.8
Chloride (mmol/L)
7.6.1.9
Cholesterol (mmol/L)
7.6.1.10
Creatine Kinase (U/L)
7.6.1.11
Creatinine (umol/L)
7.6.1.12
Gamma Glutamyl Transferase (U/L)
7.6.1.13
Glucose (mmol/L)
7.6.1.14
Phosphate (mmol/L)
7.6.1.15
Potassium (mmol/L)
7.6.1.16
Protein (g/L)
7.6.1.17
Sodium (mmol/L)
7.6.1.18
Urate (umol/L)
7.6.2
HEMATOLOGY
7.6.2.1
Anisocytes ()
7.6.2.2
Basophils (GI/L)
7.6.2.3
Eosinophils (GI/L)
7.6.2.4
Ery Mean Corpuscular Hemoglobin (fmol(Fe))
7.6.2.5
Ery Mean Corpuscular HGB Concentration (mmol/L)
7.6.2.6
Ery Mean Corpuscular Volume (fL)
7.6.2.7
Erythrocytes (TI/L)
7.6.2.8
Hematocrit (1)
7.6.2.9
Hemoglobin (mmol/L)
7.6.2.10
Leukocytes (GI/L)
7.6.2.11
Lymphocytes (GI/L)
7.6.2.12
Macrocytes ()
7.6.2.13
Microcytes ()
7.6.2.14
Monocytes (GI/L)
7.6.2.15
Platelet (GI/L)
7.6.2.16
Poikilocytes ()
7.6.2.17
Polychromasia ()
7.6.3
Not Coded
7.6.3.1
Hemoglobin A1C (1)
7.6.4
OTHER
7.6.4.1
Thyrotropin (mU/L)
7.6.4.2
Vitamin B12 (pmol/L)
7.6.5
URINALYSIS
7.6.5.1
Ketones ()
7.6.5.2
pH ()
7.6.5.3
Specific Gravity ()
7.6.5.4
Urobilinogen ()
8
Efficacy
8.1
Efficacy aggregate profiles
8.1.1
ALZHEIMER’S DISEASE ASSESSMENT SCALE
8.1.1.1
ADAS-COG(11) Subscore
8.1.2
CLINICIAN’S INTERVIEW-BASED IMPRESSION OF CHANGE (CIBIC+)
8.1.2.1
EXTENT OF CHANGE, IF ANY, SINCE BASELINE
8.1.3
NEUROPSYCHIATRIC INVENTORY - REVISED (NPI-X)
8.1.3.1
NPI-X (9) Total Score
9
Appendix
9.1
Session information
7.3.1.1
Alanine Aminotransferase (U/L)