Trial Outcomes & Findings for Real World Data on Gi(l)Otrif® Dose Adjustment (NCT NCT02751879)

Last Updated: 2019-08-08

Results Overview

An adverse drug reaction (ADR) is defined as a response to a medicinal product which is noxious and unintended. Grade 1, Grade 2, Grade 3 and Grade 4 ADR severity classes were considered for assessment of this outcome.

Recruitment status

COMPLETED

Target enrollment

228 participants

Primary outcome timeframe

From signing the informed consent onwards until the end of the study, up to 104 weeks.

Results posted on

2019-08-08

Participant Flow

This is a non-interventional, multi-country, multi-site study based on existing data from medical records of patients treated with Gi(l)otrif® tablet once daily as indicated in the approved labels. Between December 2016 and October 2017, 231 patients were screened for study participation and 228 patients were treated.

All patients were screened for eligibility to participate in the study. Patients attended specialist sites which would then ensure that all patients met all inclusion/exclusion criteria. Patients were not to be entered to study if any of the specific entry criteria were violated.

Participant milestones

Participant milestones
Measure	Gi(l)Otrif ≥ 40 mg Patients were orally treated with starting dose of greater than or equal to 40 mg Gi(l)otrif tablet once daily.	Gi(l)Otrif ≤ 30 mg Patients were orally treated with starting dose of less than or equal to 30 mg Gi(l)otrif tablet once daily.
Overall Study STARTED	157	71
Overall Study On Treatment at Study Completion	81	41
Overall Study COMPLETED	157	71
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

FAS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gi(l)Otrif ≥ 40 mg n=157 Participants Patients were orally treated with starting dose of greater than or equal to 40 mg Gi(l)otrif tablet once daily.	Gi(l)Otrif ≤ 30 mg n=71 Participants Patients were orally treated with starting dose of less than or equal to 30 mg Gi(l)otrif tablet once daily.	Total n=228 Participants Total of all reporting groups
Age, Continuous	64.50 Years STANDARD_DEVIATION 12.00 • n=99 Participants • FAS	68.10 Years STANDARD_DEVIATION 10.84 • n=107 Participants • FAS	65.62 Years STANDARD_DEVIATION 11.74 • n=206 Participants • FAS
Sex: Female, Male Female	90 Participants n=99 Participants • FAS	48 Participants n=107 Participants • FAS	138 Participants n=206 Participants • FAS
Sex: Female, Male Male	67 Participants n=99 Participants • FAS	23 Participants n=107 Participants • FAS	90 Participants n=206 Participants • FAS
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=99 Participants • FAS	9 Participants n=107 Participants • FAS	25 Participants n=206 Participants • FAS
Ethnicity (NIH/OMB) Not Hispanic or Latino	120 Participants n=99 Participants • FAS	56 Participants n=107 Participants • FAS	176 Participants n=206 Participants • FAS
Ethnicity (NIH/OMB) Unknown or Not Reported	21 Participants n=99 Participants • FAS	6 Participants n=107 Participants • FAS	27 Participants n=206 Participants • FAS
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants • FAS	0 Participants n=107 Participants • FAS	1 Participants n=206 Participants • FAS
Race (NIH/OMB) Asian	74 Participants n=99 Participants • FAS	26 Participants n=107 Participants • FAS	100 Participants n=206 Participants • FAS
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants • FAS	1 Participants n=107 Participants • FAS	1 Participants n=206 Participants • FAS
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants • FAS	0 Participants n=107 Participants • FAS	1 Participants n=206 Participants • FAS
Race (NIH/OMB) White	59 Participants n=99 Participants • FAS	37 Participants n=107 Participants • FAS	96 Participants n=206 Participants • FAS
Race (NIH/OMB) More than one race	0 Participants n=99 Participants • FAS	0 Participants n=107 Participants • FAS	0 Participants n=206 Participants • FAS
Race (NIH/OMB) Unknown or Not Reported	22 Participants n=99 Participants • FAS	7 Participants n=107 Participants • FAS	29 Participants n=206 Participants • FAS

PRIMARY outcome

Timeframe: From signing the informed consent onwards until the end of the study, up to 104 weeks.

Population: Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l)otrif®.

Outcome measures

Outcome measures
Measure	Gi(l)Otrif ≥ 40 mg n=157 Participants Patients were orally treated with starting dose of greater than or equal to 40 mg Gi(l)otrif tablet once daily.	Gi(l)Otrif ≤ 30 mg n=71 Participants Patients were orally treated with starting dose of less than or equal to 30 mg Gi(l)otrif tablet once daily.
Percentage of Patients With Adverse Drug Reactions (ADR) by Severity Class. Grade 1	21.02 Percentage of patients (%)	21.13 Percentage of patients (%)
Percentage of Patients With Adverse Drug Reactions (ADR) by Severity Class. Grade 2	44.59 Percentage of patients (%)	57.75 Percentage of patients (%)
Percentage of Patients With Adverse Drug Reactions (ADR) by Severity Class. Grade 3	24.84 Percentage of patients (%)	16.90 Percentage of patients (%)
Percentage of Patients With Adverse Drug Reactions (ADR) by Severity Class. Grade 4	3.18 Percentage of patients (%)	0.00 Percentage of patients (%)

PRIMARY outcome

Timeframe: From first dose of Gi(l)otrif® treatment to last dose of Gi(l)otrif® treatment, up to 104 weeks.

Population: FAS

Time on treatment with Gi(l)otrif® in real-world setting has been calculated in this assessment. Time on treatment refers to time to treatment failure with Gi(l)otrif®

Outcome measures

Outcome measures
Measure	Gi(l)Otrif ≥ 40 mg n=157 Participants Patients were orally treated with starting dose of greater than or equal to 40 mg Gi(l)otrif tablet once daily.	Gi(l)Otrif ≤ 30 mg n=71 Participants Patients were orally treated with starting dose of less than or equal to 30 mg Gi(l)otrif tablet once daily.
Time on Treatment With Gi(l)Otrif®	18.22 Months Interval 14.61 to 21.51	19.41 Months Interval 12.93 to The upper limit of the Confidence Interval has not being reached.

PRIMARY outcome

Timeframe: From first dose of Gi(l)otrif® treatment to last dose of Gi(l)otrif® treatment, up to 104 weeks.

Population: FAS

Time to progression was calculated from the date of first dose of Gi(l)otrif® treatment to the earliest date of documented progression (clinical, radiographic or both clinical/radiographic progression) or tumour-related death, whatever occurred first.

Outcome measures

Outcome measures
Measure	Gi(l)Otrif ≥ 40 mg n=157 Participants Patients were orally treated with starting dose of greater than or equal to 40 mg Gi(l)otrif tablet once daily.	Gi(l)Otrif ≤ 30 mg n=71 Participants Patients were orally treated with starting dose of less than or equal to 30 mg Gi(l)otrif tablet once daily.
Time to Progression With Gi(l)Otrif®	20.03 Months Interval 18.22 to 23.98	25.92 Months Interval 17.3 to The upper limit of the Confidence Interval has not being reached.

SECONDARY outcome

Timeframe: From first dose of Gi(l)otrif® treatment to last dose of Gi(l)otrif® treatment, up to 104 weeks.

Population: FAS

Percentage of patients with a modified starting dose that is dose other than the recommended 40 mg daily of Gi(l)otrif® has been calculated to assess this outcome measure.

Outcome measures

Outcome measures
Measure	Gi(l)Otrif ≥ 40 mg n=73 Participants Patients were orally treated with starting dose of greater than or equal to 40 mg Gi(l)otrif tablet once daily.	Gi(l)Otrif ≤ 30 mg Patients were orally treated with starting dose of less than or equal to 30 mg Gi(l)otrif tablet once daily.
Percentage of Patients With a Modified Starting Dose of Gi(l)Otrif® 50 mg	2.74 Percentage of patients (%)	—
Percentage of Patients With a Modified Starting Dose of Gi(l)Otrif® 30 mg	94.52 Percentage of patients (%)	—
Percentage of Patients With a Modified Starting Dose of Gi(l)Otrif® 20 mg	2.74 Percentage of patients (%)	—

SECONDARY outcome

Timeframe: From first dose of Gi(l)otrif® treatment to last dose of Gi(l)otrif® treatment, up to 104 weeks.

Population: FAS

Different reasons for starting dose with modified dose that is dose other than recommended 40 mg once daily.

Outcome measures

Outcome measures
Measure	Gi(l)Otrif ≥ 40 mg n=2 Participants Patients were orally treated with starting dose of greater than or equal to 40 mg Gi(l)otrif tablet once daily.	Gi(l)Otrif ≤ 30 mg n=71 Participants Patients were orally treated with starting dose of less than or equal to 30 mg Gi(l)otrif tablet once daily.
Percentage of Patients With Reasons for Modified Starting Dose of Gi(l)Otrif® Patient's condition	0.00 Percentage of patients (%)	38.03 Percentage of patients (%)
Percentage of Patients With Reasons for Modified Starting Dose of Gi(l)Otrif® Other	0.00 Percentage of patients (%)	40.85 Percentage of patients (%)
Percentage of Patients With Reasons for Modified Starting Dose of Gi(l)Otrif® Previous experience with EGFR-TKI	0.00 Percentage of patients (%)	5.63 Percentage of patients (%)
Percentage of Patients With Reasons for Modified Starting Dose of Gi(l)Otrif® Institutional standard	100.00 Percentage of patients (%)	15.49 Percentage of patients (%)

Adverse Events

Gi(l)Otrif ≥ 40 mg

Serious events: 11 serious events

Other events: 147 other events

Deaths: 8 deaths

Gi(l)Otrif ≤ 30 mg

Serious events: 7 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Gi(l)Otrif ≥ 40 mg n=157 participants at risk Patients were orally treated with starting dose of greater than or equal to 40 mg Gi(l)otrif tablet once daily.	Gi(l)Otrif ≤ 30 mg n=71 participants at risk Patients were orally treated with starting dose of less than or equal to 30 mg Gi(l)otrif tablet once daily.
Gastrointestinal disorders Diarrhoea	76.4% 120/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	71.8% 51/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Gastrointestinal disorders Stomatitis	37.6% 59/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	28.2% 20/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Infections and infestations Paronychia	50.3% 79/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	54.9% 39/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Infections and infestations Rash pustular	7.0% 11/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	5.6% 4/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Skin and subcutaneous tissue disorders Alopecia	3.8% 6/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	9.9% 7/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Skin and subcutaneous tissue disorders Dermatitis acneiform	46.5% 73/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	45.1% 32/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Skin and subcutaneous tissue disorders Dry skin	10.8% 17/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	7.0% 5/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Skin and subcutaneous tissue disorders Pruritus	11.5% 18/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	16.9% 12/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Skin and subcutaneous tissue disorders Rash maculo-papular	10.2% 16/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	11.3% 8/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Gastrointestinal disorders Nausea	1.9% 3/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	7.0% 5/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Nervous system disorders Dysgeusia	1.3% 2/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	5.6% 4/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Skin and subcutaneous tissue disorders Nail ridging	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	5.6% 4/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.

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 Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Gi(l)Otrif ≥ 40 mg n=157 participants at risk Patients were orally treated with starting dose of greater than or equal to 40 mg Gi(l)otrif tablet once daily.	Gi(l)Otrif ≤ 30 mg n=71 participants at risk Patients were orally treated with starting dose of less than or equal to 30 mg Gi(l)otrif tablet once daily.
Blood and lymphatic system disorders Leukocytosis	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Gastrointestinal disorders Constipation	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Gastrointestinal disorders Diarrhoea	3.8% 6/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	5.6% 4/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Gastrointestinal disorders Dysphagia	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Gastrointestinal disorders Nausea	0.00% 0/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	2.8% 2/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Gastrointestinal disorders Pancreatitis	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Gastrointestinal disorders Stomatitis	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
General disorders Pain	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
General disorders Sudden death	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Infections and infestations Abscess	0.00% 0/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	1.4% 1/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Metabolism and nutrition disorders Hyponatraemia	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.
Vascular disorders Embolism	0.64% 1/157 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.	0.00% 0/71 • From signing the informed consent onwards until the end of the study, up to 104 weeks. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Full Analysis set (FAS): All registered patients with informed consent (as applicable with local regulations) and at least one administration of Gi(l) otrif® was used for this assessment. This was a single-arm retrospective analysis.