Trial Outcomes & Findings for STudy to vAlidate telemetRic ECG Systems for firsT Dose Administration of Fingolimod (START) (NCT NCT01585298)

NCT ID: NCT01585298

Last Updated: 2019-09-23

Results Overview

AV Blocks/Heart block is an abnormal heart rhythm where the heart beats too slowly; the electrical signals that tell the heart to contract are partially intermittent (Type 2:1) or slowed (1st and 2nd degree) or blocked (3rd degree) between the upper chambers (atria) and the lower chambers (ventricles). In 2nd degree AV Blocks, electrical impulses are intermittent (type 2:1) or delayed w/ each subsequent heartbeat (Mobitz type I) until a beat fails to reach the ventricles entirely. This type of block often is physiologic and observed in a highly relaxed state \& during sleep. In 2nd degree AV Blocks type II, the atria electrical impulses are unable to reach the ventricles, a more serious condition. In 3rd degree AV Blocks (complete heart block), none of the electrical impulses reach either the atria or the ventricles. Patients can experience simultaneously both types of 2nd or 3rd degree AV Blocks without any symptoms.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 6998 participants
• Primary outcome timeframe: baseline, during 6 hour monitoring post first dose observation
• Results posted on: 2019-09-23

Participant Flow

6998 participants were enrolled into the study and were considered as part of the safety set, but 2 participants discontinued from the study and did not take any study drug.

Participant milestones

Measure	Fingolimod Fingolimod 0.5 mg by mouth once daily for 7 days.
Overall Study STARTED	6998
Overall Study COMPLETED	6961
Overall Study NOT COMPLETED	37

Reasons for withdrawal

Measure	Fingolimod Fingolimod 0.5 mg by mouth once daily for 7 days.
Overall Study Study completion was not documented.	1
Overall Study Protocol deviation	1
Overall Study Administrative problems	4
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	4
Overall Study Abnormal test procedure results	1
Overall Study Adverse Event	24

Baseline Characteristics

STudy to vAlidate telemetRic ECG Systems for firsT Dose Administration of Fingolimod (START)

Baseline characteristics by cohort

Measure	Fingolimod n=6998 Participants Fingolimod 0.5 mg by mouth once daily for 7 days.
Age, Continuous	39.2 Years STANDARD_DEVIATION 10.52 • n=5 Participants
Sex: Female, Male Female	4924 Participants n=5 Participants
Sex: Female, Male Male	2074 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, during 6 hour monitoring post first dose observation

Population: Safety set: The safety set consisted of all enrolled participants for whom safety information was collected. Two patients of the safety analysis set discontinued the study without having received treatment, but safety information was collected on these two patients.

AV Blocks/Heart block is an abnormal heart rhythm where the heart beats too slowly; the electrical signals that tell the heart to contract are partially intermittent (Type 2:1) or slowed (1st and 2nd degree) or blocked (3rd degree) between the upper chambers (atria) and the lower chambers (ventricles). In 2nd degree AV Blocks, electrical impulses are intermittent (type 2:1) or delayed w/ each subsequent heartbeat (Mobitz type I) until a beat fails to reach the ventricles entirely. This type of block often is physiologic and observed in a highly relaxed state & during sleep. In 2nd degree AV Blocks type II, the atria electrical impulses are unable to reach the ventricles, a more serious condition. In 3rd degree AV Blocks (complete heart block), none of the electrical impulses reach either the atria or the ventricles. Patients can experience simultaneously both types of 2nd or 3rd degree AV Blocks without any symptoms.

Outcome measures

Measure	Fingolimod n=6998 Participants Fingolimod 0.5 mg by mouth once daily for 7 days.
Participants With 2nd or 3rd Degree Atrioventricular (AV) Block Any AV block ll degree or higher	120 Participants
Participants With 2nd or 3rd Degree Atrioventricular (AV) Block AV block ll degree: Mobitz type I degree	117 Participants
Participants With 2nd or 3rd Degree Atrioventricular (AV) Block AV block II degree: Mobitz type II degree	0 Participants
Participants With 2nd or 3rd Degree Atrioventricular (AV) Block AV block II degree: 2:1	43 Participants
Participants With 2nd or 3rd Degree Atrioventricular (AV) Block AV block III degree	1 Participants

PRIMARY outcome

Timeframe: baseline during 6 hour monitoring post dose

Population: Safety set: The safety set consisted of all enrolled participants for whom safety information was collected. Two patients of the safety analysis set discontinued the study without having received treatment, but safety information was collected on these two patients.

Number of patients with heart rate below 45 beats bpm in ECG during first dose observation

Outcome measures

Measure	Fingolimod n=6998 Participants Fingolimod 0.5 mg by mouth once daily for 7 days.
Number of Patients With Heart Rate Below 45 Beats Per Minute (BPM)	63 Participants

SECONDARY outcome

Timeframe: baseline post-dose

Population: The safety set, which consisted of all enrolled participants for whom safety information was collected, was considered for the analysis. Only participants, who had baseline post-dose QTc interval data, were analyzed. Of the 6998 patients, 6844 patients had complete baseline post-dose QTc interval data.

Number of patients with conduction abnormalities such as QT prolongation, first degree AV block during treatment initiation.

The QT interval is a period between the activation and the regeneration of ventricular contraction. A prolonged QT interval can be a potential marker of cardiac arrhythmias.

Two patients of the safety analysis set discontinued the study without having received treatment, but safety information was collected on these two patients.

Outcome measures

Measure	Fingolimod n=6844 Participants Fingolimod 0.5 mg by mouth once daily for 7 days.
Number of Participants With Prolonged QTc Interval (Friderica) Female, QTcFridericia Interval > 470 ms	7 Participants
Number of Participants With Prolonged QTc Interval (Friderica) Male, QTcF Interval > 450 ms	6 Participants

SECONDARY outcome

Timeframe: up to day 7

Population: Safety set: The safety set consisted of all enrolled participants for whom safety information was collected. Two patients of the safety analysis set discontinued the study without having received treatment, but safety information was collected on these two patients.

The number of participants with bradyarrhythmic electrocardiogram (ECG) events was assessed. Bradyarrhythmic ECG events are defined as QTc Fridericia time > 450 ms for males and > 470 ms for females.

Outcome measures

Measure	Fingolimod n=6998 Participants Fingolimod 0.5 mg by mouth once daily for 7 days.
Number of Participants With Bradyarrhythmic Electrocardiogram (ECG) Events	26 Participants

SECONDARY outcome

Timeframe: 7 days

Population: Safety set: The safety set consisted of all enrolled participants for whom safety information was collected. Two patients of the safety analysis set discontinued the study without having received treatment, but safety information was collected on these two patients.

The number of participants with the occurrence of subsequent cardiac adverse events (AEs) and serious cardiac AEs during study was assessed. Cardiac events were defined as the following Medical Dictionary for Regulatory Activities (MedDRA) preferred terms: angina pectoris, chest discomfort, dizziness, dyspnoea, dyspnoea exertional, fatigue, palpitations, syncope, vertigo, vertigo positional and vision blurred.

Outcome measures

Measure	Fingolimod n=6998 Participants Fingolimod 0.5 mg by mouth once daily for 7 days.
Number of Patients With Cardiac Adverse Events Cardiac events	489 Participants
Number of Patients With Cardiac Adverse Events Serious cardiac AEs	9 Participants

Adverse Events

Fingolimod

Serious events: 160 serious events

Other events: 2179 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fingolimod n=6998 participants at risk Fingolimod 0.5 mg by mouth once daily for 7 days.
Blood and lymphatic system disorders Leukocytosis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Arrhythmia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Leukopenia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Atrial fibrillation	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Lymphopenia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Angina pectoris	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Atrioventricular block complete	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Atrioventricular block second degree	0.70% 49/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Bradycardia	0.34% 24/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Coronary artery disease	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Ischaemic cardiomyopathy	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Myocardial infarction	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Sinus bradycardia	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Supraventricular extrasystoles	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Ear and labyrinth disorders Vertigo	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Macular oedema	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Visual acuity reduced	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Abdominal discomfort	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Anal fistula	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Diarrhoea	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Dysphagia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Mouth haemorrhage	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Nausea	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Pancreatitis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Fatigue	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders General physical health deterioration	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Malaise	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Non-cardiac chest pain	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Pyrexia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Abdominal abscess	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Anal abscess	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Cellulitis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Cystitis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Gastroenteritis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Herpes zoster	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Infection	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Oral herpes	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Pyelonephritis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Subdural haematoma	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Tendon rupture	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Upper limb fracture	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations CD4/CD8 ratio decreased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Electrocardiogram QT prolonged	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Gamma-glutamyltransferase increased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Heart rate decreased	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Muscle spasms	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Myalgia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm benign	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Ataxia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Central nervous system lesion	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Dizziness	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Embolic cerebral infarction	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Epilepsy	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Headache	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Hypoaesthesia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Intracranial aneurysm	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Multiple sclerosis relapse	0.37% 26/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Optic neuritis	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Partial seizures	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Restless legs syndrome	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Seizure	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Subdural hygroma	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Syncope	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Pregnancy, puerperium and perinatal conditions Unintended pregnancy	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Borderline personality disorder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Depression suicidal	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Mental fatigue	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Panic attack	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Renal and urinary disorders Calculus urethral	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Painful respiration	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Respiratory tract inflammation	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Skin irritation	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Blood pressure fluctuation	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Hypertension	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Hypertensive crisis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.

Other adverse events

Measure	Fingolimod n=6998 participants at risk Fingolimod 0.5 mg by mouth once daily for 7 days.
Psychiatric disorders Anxiety	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Depressed mood	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Depression	0.27% 19/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Dyssomnia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Mental disorder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Emotional disorder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Initial insomnia	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Insomnia	0.17% 12/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Irritability	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Laziness	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Listless	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Anaemia	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Eosinopenia	0.10% 7/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Eosinophilia	0.17% 12/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Granulocytosis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Haemoglobinaemia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Leukocytosis	0.16% 11/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Leukopenia	0.97% 68/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Lymphadenopathy	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Lymphopenia	1.7% 119/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Microcytic anaemia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Monocytopenia	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Monocytosis	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Neutropenia	0.13% 9/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Neutrophilia	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Pancytopenia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Blood and lymphatic system disorders Thrombocytopenia	0.10% 7/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Angina pectoris	0.16% 11/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Arrhythmia	0.10% 7/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Atrioventricular block first degree	1.7% 116/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Atrioventricular block second degree	1.1% 74/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Bradycardia	0.69% 48/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Bundle branch block right	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Cardiac discomfort	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Cardiovascular disorder	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Coronary artery stenosis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Extrasystoles	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Palpitations	0.37% 26/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Pericardial effusion	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Sinus arrhythmia	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Sinus bradycardia	0.11% 8/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Sinus tachycardia	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Supraventricular extrasystoles	0.14% 10/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Tachycardia	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Ventricular extrasystoles	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Ventricular pre-excitation	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Cardiac disorders Ventricular tachycardia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Congenital, familial and genetic disorders Corneal dystrophy	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Ear and labyrinth disorders Deafness	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Ear and labyrinth disorders Ear discomfort	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Ear and labyrinth disorders Ear pain	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Ear and labyrinth disorders External ear inflammation	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Ear and labyrinth disorders Sudden hearing loss	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Ear and labyrinth disorders Tinnitus	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Ear and labyrinth disorders Vertigo	0.97% 68/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Ear and labyrinth disorders Vertigo positional	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Amblyopia	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Blepharospasm	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Cataract	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Diplopia	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Eye irritation	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Eye pain	0.16% 11/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Eye swelling	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Eyelid oedema	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Foreign body sensation in eyes	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Iridocyclitis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Macular oedema	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Ocular discomfort	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Photopsia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Retinal vein thrombosis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Vision blurred	0.29% 20/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Visual acuity reduced	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Eye disorders Visual impairment	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Abdominal discomfort	0.13% 9/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Abdominal distension	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Abdominal pain	0.13% 9/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Abdominal pain lower	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Abdominal pain upper	0.76% 53/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Anal incontinence	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Aphthous ulcer	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Bowel movement irregularity	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Constipation	0.19% 13/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Diarrhoea	1.4% 96/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Dry mouth	0.10% 7/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Dyspepsia	0.16% 11/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Dysphagia	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Enteritis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Eructation	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Faeces soft	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Flatulence	0.13% 9/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Frequent bowel movements	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Gastric disorder	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Gastritis	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Gastrointestinal disorder	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Gastrointestinal erosion	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Haemorrhoids	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Nausea	2.0% 143/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Odynophagia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Oral dysaesthesia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Oral pain	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Oral pruritus	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Paraesthesia oral	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Tongue blistering	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Tooth disorder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Toothache	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Gastrointestinal disorders Vomiting	0.19% 13/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Application site reaction	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Asthenia	0.14% 10/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Chest discomfort	0.34% 24/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Chest pain	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Chills	0.16% 11/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Chronic fatigue syndrome	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Discomfort	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Face oedema	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Fatigue	3.2% 227/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Feeling abnormal	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Feeling cold	0.11% 8/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Feeling drunk	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Feeling hot	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Gait disturbance	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Inflammation	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Influenza like illness	0.27% 19/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Infusion site inflammation	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Infusion site necrosis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Local swelling	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Malaise	0.16% 11/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Mucosal dryness	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Non-cardiac chest pain	0.44% 31/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Oedema peripheral	0.10% 7/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Pain	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Peripheral swelling	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Pyrexia	0.24% 17/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Secretion discharge	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Sensation of foreign body	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Sense of oppression	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Temperature intolerance	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
General disorders Thirst	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Hepatobiliary disorders Hepatic steatosis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Hepatobiliary disorders Hyperbilirubinaemia	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Hepatobiliary disorders Liver disorder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Immune system disorders Food allergy	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Immune system disorders Hypersensitivity	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Immune system disorders Seasonal allergy	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Anal abscess	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Anorectal infection	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Bacterial infection	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Bronchitis	0.10% 7/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Chronic sinusitis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Conjunctivitis	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Cystitis	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Dysentery	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Erysipelas	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Febrile infection	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Fungal infection	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Gastroenteritis	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Gastroenteritis viral	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Gastrointestinal infection	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Genital herpes	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Genitourinary tract infection	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Gingivitis	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Helminthic infection	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Herpes simplex	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Herpes virus infection	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Herpes zoster	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Hordeolum	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Infected bite	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Infection	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Influenza	0.33% 23/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Laryngitis	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Mastoiditis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Myelitis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Nasopharyngitis	2.0% 137/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Onychomycosis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Oral herpes	0.39% 27/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Pharyngitis	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Pyelonephritis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Respiratory tract infection	0.10% 7/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Rhinitis	0.17% 12/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Sialoadenitis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Sinusitis	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Tinea versicolour	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Tonsillitis	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Upper respiratory tract infection	0.17% 12/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Urinary tract infection	0.21% 15/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Vaginal abscess	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Viral infection	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Viral rhinitis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Vulvovaginal candidiasis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Infections and infestations Vulvovaginal mycotic infection	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Animal bite	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Animal scratch	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Chest injury	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Fall	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Foot fracture	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Laceration	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Ligament sprain	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Limb injury	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Meniscus injury	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Post procedural complication	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Skin abrasion	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Injury, poisoning and procedural complications Thermal burn	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Alanine aminotransferase increased	0.30% 21/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Aspartate aminotransferase increased	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Basophil count increased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Blood alkaline phosphatase increased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Blood bilirubin increased	0.16% 11/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Blood chloride decreased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Blood creatinine increased	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Blood glucose decreased	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Blood glucose increased	0.13% 9/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Blood pressure decreased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Blood pressure diastolic decreased	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Blood pressure diastolic increased	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Blood pressure increased	0.14% 10/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Blood pressure systolic increased	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Blood urea increased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Body temperature increased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Electrocardiogram P wave abnormal	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Electrocardiogram QRS complex prolonged	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Electrocardiogram QT prolonged	0.13% 9/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Electrocardiogram ST segment abnormal	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Electrocardiogram ST segment depression	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Electrocardiogram T wave inversion	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Electrocardiogram abnormal	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Eosinophil count decreased	0.19% 13/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Eosinophil count increased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Gamma-glutamyltransferase increased	0.11% 8/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Haematocrit decreased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Haematocrit increased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Haemoglobin decreased	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Haemoglobin increased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Heart rate abnormal	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Heart rate decreased	0.19% 13/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Heart rate increased	0.10% 7/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Hepatic enzyme increased	0.20% 14/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Liver function test increased	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Lymphocyte count abnormal	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Lymphocyte count decreased	0.51% 36/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Lymphocyte count increased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Monocyte count decreased	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Monocyte count increased	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Neutrophil count decreased	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Neutrophil count increased	0.10% 7/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Platelet aggregation	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Platelet count decreased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Pulse abnormal	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Red blood cell count decreased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Transaminases increased	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Weight decreased	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations Weight increased	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations White blood cell count decreased	0.26% 18/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations White blood cell count increased	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Investigations White blood cells urine	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Metabolism and nutrition disorders Decreased appetite	0.13% 9/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Metabolism and nutrition disorders Food craving	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Metabolism and nutrition disorders Gluten sensitivity	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Metabolism and nutrition disorders Hyperglycaemia	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Metabolism and nutrition disorders Hyperkalaemia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Metabolism and nutrition disorders Hypoglycaemia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Metabolism and nutrition disorders Hypokalaemia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Metabolism and nutrition disorders Increased appetite	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Metabolism and nutrition disorders Vitamin D deficiency	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Arthralgia	0.23% 16/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Arthritis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Back pain	0.66% 46/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Bone pain	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Bursitis	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Coccydynia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Flank pain	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Groin pain	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Joint stiffness	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Limb discomfort	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Mobility decreased	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Muscle fatigue	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Muscle rigidity	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Muscle spasms	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Muscle tightness	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Muscle twitching	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Muscular weakness	0.11% 8/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Myalgia	0.23% 16/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Myofascial pain syndrome	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Neck pain	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Pain in extremity	0.27% 19/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Musculoskeletal and connective tissue disorders Spinal disorder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pharyngeal neoplasm benign	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Aphasia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Ataxia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Balance disorder	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Carpal tunnel syndrome	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Disturbance in attention	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Dizziness	1.8% 126/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Dizziness exertional	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Dizziness postural	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Dysaesthesia	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Dysgeusia	0.30% 21/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Epilepsy	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Facial spasm	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Head discomfort	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Headache	4.5% 316/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Hemiparesis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Hyperaesthesia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Hypertonia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Hypoaesthesia	0.20% 14/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Lhermitte's sign	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Migraine	0.24% 17/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Migraine with aura	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Monoparesis	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Multiple sclerosis	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Multiple sclerosis relapse	1.0% 70/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Muscle spasticity	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Neuralgia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Neuropathy peripheral	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Optic neuritis	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Orthostatic intolerance	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Paraesthesia	0.41% 29/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Peroneal nerve palsy	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Presyncope	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Psychogenic pseudosyncope	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Radial nerve compression	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Restless legs syndrome	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Sciatica	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Sensory disturbance	0.10% 7/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Somnolence	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Syncope	0.07% 5/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Tension headache	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Tremor	0.13% 9/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Trigeminal neuralgia	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Nervous system disorders Visual field defect	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Pregnancy, puerperium and perinatal conditions Pregnancy of unknown location	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Pregnancy, puerperium and perinatal conditions Unintended pregnancy	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Product Issues Device defective	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Adjustment disorder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Adjustment disorder with depressed mood	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Affective disorder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Aggression	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Agitation	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Mental fatigue	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Middle insomnia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Mood altered	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Mood swings	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Nervousness	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Nightmare	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Panic attack	0.10% 7/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Persistent depressive disorder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Restlessness	0.11% 8/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Psychiatric disorders Sleep disorder	0.26% 18/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Renal and urinary disorders Bladder dysfunction	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Renal and urinary disorders Dysuria	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Renal and urinary disorders Haematuria	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Renal and urinary disorders Micturition urgency	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Renal and urinary disorders Nephritis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Renal and urinary disorders Neurogenic bladder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Renal and urinary disorders Nocturia	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Renal and urinary disorders Pollakiuria	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Renal and urinary disorders Renal pain	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Renal and urinary disorders Urge incontinence	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Reproductive system and breast disorders Breast discomfort	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Reproductive system and breast disorders Breast disorder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Reproductive system and breast disorders Breast pain	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Reproductive system and breast disorders Breast tenderness	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Reproductive system and breast disorders Cervical dysplasia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Reproductive system and breast disorders Dysmenorrhoea	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Reproductive system and breast disorders Metrorrhagia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Reproductive system and breast disorders Ovulation pain	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Reproductive system and breast disorders Priapism	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Reproductive system and breast disorders Uterine haemorrhage	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Reproductive system and breast disorders Vulvovaginal burning sensation	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Allergic bronchitis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Asthma	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Cough	0.29% 20/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.26% 18/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.09% 6/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Increased bronchial secretion	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Nasal oedema	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.39% 27/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Painful respiration	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Sinus disorder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Respiratory, thoracic and mediastinal disorders Throat tightness	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Acne	0.11% 8/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Alopecia	0.21% 15/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Blister	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Dermatitis	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Dermatitis contact	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Dermatitis exfoliative	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Dermatosis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Drug eruption	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Dry skin	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Dyshidrotic eczema	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Eczema	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Erythema	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Hand dermatitis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.20% 14/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Night sweats	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Photosensitivity reaction	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Pigmentation disorder	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Pityriasis rosea	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Pruritus	0.34% 24/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Pruritus generalised	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Rash	0.21% 15/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Rash pruritic	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Rash vesicular	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Rosacea	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Skin burning sensation	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Skin disorder	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Skin exfoliation	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Skin irritation	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Skin odour abnormal	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Skin reaction	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Skin and subcutaneous tissue disorders Swelling face	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Social circumstances Walking disability	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Blood pressure fluctuation	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Circulatory collapse	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Diastolic hypertension	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Flushing	0.06% 4/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Haematoma	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Hot flush	0.04% 3/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Hypertension	0.91% 64/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Hypotension	0.17% 12/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Pallor	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Peripheral coldness	0.03% 2/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.
Vascular disorders Varicose vein	0.01% 1/6998 • Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER