Trial Outcomes & Findings for GIOTRIF rPMS in Korean Patients With NSCLC (NCT NCT02285361)

NCT ID: NCT02285361

Last Updated: 2021-02-24

Results Overview

Percentage of participants with Adverse Drug Reactions (ADRs).

Recruitment status

COMPLETED

Target enrollment

1272 participants

Primary outcome timeframe

From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days.

Results posted on

2021-02-24

Participant Flow

This is an observational prospective, non-interventional, open-label, multi-centre national study in Korean patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) mutations or patients with locally advanced or metastatic NSCLC of squamous histology progressing on or after platinum-based chemotherapy

All subjects were screened for eligibility prior to participation in the trial. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Participant milestones
Measure	GIOTRIF® GIOTRIF® was prescribed according to the local label and at the discretion of the treating physician. The physicians indicated doses and timing based on the current authorized label in Korea. Possible dosage were 20 milligram (mg), 30 mg and 40 mg administered orally, once daily, at least 1 hour before a meal or at least 3 hours after a meal, taken without food and swallowed whole with water.
Overall Study STARTED	1272
Overall Study COMPLETED	1221
Overall Study NOT COMPLETED	51

Reasons for withdrawal

Reasons for withdrawal
Measure	GIOTRIF® GIOTRIF® was prescribed according to the local label and at the discretion of the treating physician. The physicians indicated doses and timing based on the current authorized label in Korea. Possible dosage were 20 milligram (mg), 30 mg and 40 mg administered orally, once daily, at least 1 hour before a meal or at least 3 hours after a meal, taken without food and swallowed whole with water.
Overall Study Protocol Violation	43
Overall Study Lost to Follow-up	5
Overall Study Not taken GIOTRIF	2
Overall Study Consented prior to the contract date	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GIOTRIF® n=1220 Participants GIOTRIF® was prescribed according to the local label and at the discretion of the treating physician. The physicians indicated doses and timing based on the current authorized label in Korea. Possible dosage were 20 milligram (mg), 30 mg and 40 mg administered orally, once daily, at least 1 hour before a meal or at least 3 hours after a meal, taken without food and swallowed whole with water.
Age, Continuous	66.26 years STANDARD_DEVIATION 10.78 • n=1220 Participants
Sex: Female, Male Female	662 Participants n=1220 Participants
Sex: Female, Male Male	558 Participants n=1220 Participants

PRIMARY outcome

Timeframe: From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days.

Population: All Participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria. 1 subject was excluded from the set based on disease indication.

Percentage of participants with Adverse Drug Reactions (ADRs).

Outcome measures

Outcome measures
Measure	GIOTRIF® n=1220 Participants GIOTRIF® was prescribed according to the local label and at the discretion of the treating physician. The physicians indicated doses and timing based on the current authorized label in Korea. Possible dosage were 20 milligram (mg), 30 mg and 40 mg administered orally, once daily, at least 1 hour before a meal or at least 3 hours after a meal, taken without food and swallowed whole with water.
Percentage of Participants With Adverse Drug Reactions (ADRs)	89.92 Percentage of participants

SECONDARY outcome

Timeframe: From week 0 until week 48. Up to 48 weeks.

Population: Effectiveness assessment set: all participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria. 221 subjects were excluded due to missing effectiveness assessments.

Progression-Free Survival (PFS) rate, defined as the percentage of patients who were alive and without disease progression at the 48-week tumour assessment. Progression was assessed by the investigator according to local standard pattern of care for non-small cell lung cancer (NSCLC). If a patient is known to have progressed, but the date of progression is not attainable, the last date when the patient was assessed will be used as date of progression. PFS rate at 48 weeks was estimated using Kaplan-Meier estimates on the PFS curve.

Outcome measures

Outcome measures
Measure	GIOTRIF® n=1000 Participants GIOTRIF® was prescribed according to the local label and at the discretion of the treating physician. The physicians indicated doses and timing based on the current authorized label in Korea. Possible dosage were 20 milligram (mg), 30 mg and 40 mg administered orally, once daily, at least 1 hour before a meal or at least 3 hours after a meal, taken without food and swallowed whole with water.
Progression-Free Survival (PFS) Rate at 48 Weeks	73.74 Percentage of participants Interval 70.37 to 76.8

SECONDARY outcome

Timeframe: Tumour assessments performed at week 0, 8±2, 24±2 and 48±2. Up to 50 weeks.

Best response is defined as the best response observed in individual subject from the date of the first administration of the study medication until the earliest recording of Progressive disease (PD), death, or end of treatment (as long as no additional anti-cancer therapy was implemented). Disease Assessment will be based on the assessment of cancer related symptoms and, if available, radiologic assessments as per standard of care at the site. Tumour response according to investigator's assessment Each patient will be assigned to one of the following categories: 1. Complete response (CR) 2. Partial response (PR) 3. Stable disease (SD) 4. Progressive disease (PD) 5. Not evaluable for response, reasons to be specified (e.g. early death, tumour assessments incomplete, etc.)

Outcome measures

Outcome measures
Measure	GIOTRIF® n=964 Participants GIOTRIF® was prescribed according to the local label and at the discretion of the treating physician. The physicians indicated doses and timing based on the current authorized label in Korea. Possible dosage were 20 milligram (mg), 30 mg and 40 mg administered orally, once daily, at least 1 hour before a meal or at least 3 hours after a meal, taken without food and swallowed whole with water.
Percentage of Participants With Best Response Complete Response	2.90 Percentage of participants
Percentage of Participants With Best Response Partial Response	60.89 Percentage of participants
Percentage of Participants With Best Response Stable Disease	32.26 Percentage of participants
Percentage of Participants With Best Response Progressive Disease	3.22 Percentage of participants
Percentage of Participants With Best Response Not Evaluable	0.73 Percentage of participants

SECONDARY outcome

Timeframe: From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days.

Overall Survival (OS), defined as time from the date of the first administration of afatinib to the date of death. Kaplan-Meier estimates and 95% confidence intervals for the 25th, median, and 75th percentiles of the survival distribution will be calculated for OS. For patients with known date of death: OS \[days\] = date of death - (date of start of treatment) + 1 For patients known not death case: OS (censored) \[days\] = date of last contact showing no death - (date of start of treatment) + 1.

Outcome measures

Outcome measures
Measure	GIOTRIF® n=1000 Participants GIOTRIF® was prescribed according to the local label and at the discretion of the treating physician. The physicians indicated doses and timing based on the current authorized label in Korea. Possible dosage were 20 milligram (mg), 30 mg and 40 mg administered orally, once daily, at least 1 hour before a meal or at least 3 hours after a meal, taken without food and swallowed whole with water.
Overall Survival (OS)	NA Days Interval 1051.0 to The median and upper confidence interval could not be estimated due to the low number of deaths.

Adverse Events

GIOTRIF®

Serious events: 442 serious events

Other events: 1076 other events

Deaths: 52 deaths

Serious adverse events

Serious adverse events
Measure	GIOTRIF® n=1266 participants at risk GIOTRIF® was prescribed according to the local label and at the discretion of the treating physician. The physicians indicated doses and timing based on the current authorized label in Korea. Possible dosage were 20 milligram (mg), 30 mg and 40 mg administered orally, once daily, at least 1 hour before a meal or at least 3 hours after a meal, taken without food and swallowed whole with water.
Blood and lymphatic system disorders Anaemia	0.32% 4/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Blood and lymphatic system disorders Neutropenia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Blood and lymphatic system disorders Pancytopenia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Cardiac disorders Acute myocardial infarction	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Cardiac disorders Atrial flutter	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Cardiac disorders Cardiac tamponade	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Cardiac disorders Pericardial effusion	0.32% 4/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Ear and labyrinth disorders Otolithiasis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Ear and labyrinth disorders Vertigo positional	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Endocrine disorders Thyroid mass	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Eye disorders Glaucoma	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Eye disorders Retinal detachment	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Abdominal pain	0.24% 3/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Colitis	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Diarrhoea	4.2% 53/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Dysphagia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Enteritis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Enterocolitis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Gastric ulcer	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Haematochezia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Haemorrhoids	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Ileus paralytic	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Mechanical ileus	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Melaena	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Mouth ulceration	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Nausea	0.47% 6/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Stomatitis	0.39% 5/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Vomiting	0.79% 10/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
General disorders Asthenia	0.87% 11/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
General disorders Chest pain	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
General disorders Death	0.32% 4/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
General disorders Disease progression	7.8% 99/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
General disorders Fatigue	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
General disorders Gait disturbance	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
General disorders Mucosal inflammation	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
General disorders Pyrexia	0.32% 4/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Hepatobiliary disorders Cholelithiasis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Hepatobiliary disorders Drug-induced liver injury	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Hepatobiliary disorders Hepatic cirrhosis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Hepatobiliary disorders Hepatitis toxic	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Hepatobiliary disorders Hepatotoxicity	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Atypical pneumonia	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Bacteraemia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Bronchiolitis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Bronchitis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Cellulitis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Chest wall abscess	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Clostridium difficile colitis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Clostridium difficile infection	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Eczema herpeticum	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Folliculitis	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Gastroenteritis	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Infectious pleural effusion	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Onychomycosis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Paronychia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Pharyngitis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Pneumonia	2.8% 35/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Pneumonia bacterial	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Pneumonia viral	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Pseudomembranous colitis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Pyelonephritis acute	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Renal abscess	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Septic shock	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Subcutaneous abscess	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Upper respiratory tract infection	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Injury, poisoning and procedural complications Compression fracture	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Injury, poisoning and procedural complications Fall	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Injury, poisoning and procedural complications Fractured sacrum	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Injury, poisoning and procedural complications Meniscus injury	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Injury, poisoning and procedural complications Radiation pneumonitis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Injury, poisoning and procedural complications Rib fracture	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Injury, poisoning and procedural complications Spinal compression fracture	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Injury, poisoning and procedural complications Subcutaneous haematoma	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Injury, poisoning and procedural complications Subdural haemorrhage	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Investigations Alanine aminotransferase increased	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Investigations Aspartate aminotransferase increased	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Investigations Liver function test increased	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Decreased appetite	0.32% 4/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Dehydration	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Diabetes mellitus	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Hyperglycaemia	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Hyperkalaemia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Hypoglycaemia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Hyponatraemia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Hypophagia	0.32% 4/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Lactic acidosis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Malnutrition	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Metabolic acidosis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Tumour lysis syndrome	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Musculoskeletal and connective tissue disorders Arthralgia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Musculoskeletal and connective tissue disorders Back pain	0.39% 5/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Musculoskeletal and connective tissue disorders Flank pain	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Musculoskeletal and connective tissue disorders Muscular weakness	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Musculoskeletal and connective tissue disorders Neck pain	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Musculoskeletal and connective tissue disorders Pain in extremity	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Musculoskeletal and connective tissue disorders Spinal stenosis	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal gland cancer metastatic	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	7.9% 100/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.39% 5/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	1.0% 13/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pericardial effusion malignant	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Peritumoural oedema	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small intestine carcinoma metastatic	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Aphasia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Cerebral infarction	0.24% 3/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Dizziness	0.32% 4/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Embolic cerebral infarction	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Epilepsy	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Headache	0.32% 4/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Hemiparesis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Hydrocephalus	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Hypoaesthesia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Intracranial aneurysm	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Myelopathy	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Normal pressure hydrocephalus	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Seizure	0.24% 3/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Nervous system disorders Syncope	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Psychiatric disorders Bipolar disorder	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Psychiatric disorders Confusional state	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Psychiatric disorders Delirium	0.32% 4/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Psychiatric disorders Disorientation	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Psychiatric disorders Mental status changes	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Renal and urinary disorders Acute kidney injury	1.5% 19/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Renal and urinary disorders Azotaemia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Renal and urinary disorders Calculus urinary	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Renal and urinary disorders Chronic kidney disease	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Renal and urinary disorders Dysuria	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Asphyxia	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Asthma	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Cough	0.55% 7/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.3% 17/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.24% 3/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Idiopathic pulmonary fibrosis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Laryngeal oedema	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Orthopnoea	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.7% 22/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.63% 8/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.39% 5/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Productive cough	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.79% 10/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.16% 2/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Pulmonary thrombosis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Respiratory, thoracic and mediastinal disorders Wheezing	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Skin and subcutaneous tissue disorders Drug eruption	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Skin and subcutaneous tissue disorders Pain of skin	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Skin and subcutaneous tissue disorders Pruritus	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Skin and subcutaneous tissue disorders Rash	0.55% 7/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Vascular disorders Deep vein thrombosis	0.24% 3/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Vascular disorders Hypovolaemic shock	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Vascular disorders Orthostatic hypotension	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Vascular disorders Pelvic venous thrombosis	0.08% 1/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.

Other adverse events

Other adverse events
Measure	GIOTRIF® n=1266 participants at risk GIOTRIF® was prescribed according to the local label and at the discretion of the treating physician. The physicians indicated doses and timing based on the current authorized label in Korea. Possible dosage were 20 milligram (mg), 30 mg and 40 mg administered orally, once daily, at least 1 hour before a meal or at least 3 hours after a meal, taken without food and swallowed whole with water.
Gastrointestinal disorders Diarrhoea	68.4% 866/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Nausea	7.2% 91/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Gastrointestinal disorders Stomatitis	29.8% 377/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Infections and infestations Paronychia	24.8% 314/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Metabolism and nutrition disorders Decreased appetite	16.1% 204/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Skin and subcutaneous tissue disorders Pruritus	13.1% 166/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.
Skin and subcutaneous tissue disorders Rash	40.7% 515/1266 • From baseline (Visit 1) until last visit (the last follow-up visit a patient actually attended during the study), up to 1051 days. For this non interventional study, all 1272 participants whose case report forms (CRFs) were retrieved during the re-examination period (29 Jan 2014 - 28 Jan 2020) and who did not violate the inclusion/exclusion criteria were included. Among these, 6 participants were deemed not eligible retrospectively and were additionally excluded.

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place