Trial Outcomes & Findings for Selinexor Treatment of Advanced Relapsed/Refractory Squamous Cell Carcinomas (NCT NCT02213133)

Last Updated: 2023-01-26

Results Overview

DCR was defined as the best overall response of complete response (CR), partial response (PR), or stable disease (SD). CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Participant response was evaluated by physical examinations and computed tomography (CT)/Magnetic Resonance Imaging (MRI) (or optional positron emission tomography \[PET\]/CT) and assessed by RECIST 1.1 criteria.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

up to 14.6 months

Results posted on

2023-01-26

Participant Flow

The study was conducted at 14 sites in United States and 1 site in Canada between 22 September 2014 and 10 December 2015.

A total of 45 participants were enrolled and randomized.

Participant milestones

Participant milestones
Measure	Cohort 1: Head and Neck-SCC Participants with advanced squamous cell carcinoma (SCC) of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 milligrams (mg) selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets less than \[\<\] 100\*10\^9 per litre \[/L\]), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 2: Lungs-SCC Participants with advanced SCC of lungs, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 3: Esophagus-SCC Participants with advanced SCC of esophagus, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.
Overall Study STARTED	37	5	3
Overall Study Treated	33	4	1
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	37	5	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Head and Neck-SCC Participants with advanced squamous cell carcinoma (SCC) of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 milligrams (mg) selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets less than \[\<\] 100\*10\^9 per litre \[/L\]), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 2: Lungs-SCC Participants with advanced SCC of lungs, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 3: Esophagus-SCC Participants with advanced SCC of esophagus, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.
Overall Study Participant discontinued study therapy	2	0	0
Overall Study Participant withdrew informed consent	2	1	2
Overall Study Disease progression	11	2	0
Overall Study Adverse Event (AE)	1	0	0
Overall Study Death	16	2	1
Overall Study Other	5	0	0

Baseline Characteristics

Selinexor Treatment of Advanced Relapsed/Refractory Squamous Cell Carcinomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Head and Neck-SCC n=33 Participants Participants with advanced SCC of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 2: Lungs-SCC n=4 Participants Participants with advanced SCC of lungs, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 3: Esophagus-SCC n=1 Participants Participants with advanced SCC of esophagus, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Total n=38 Participants Total of all reporting groups
Age, Continuous	58.5 years STANDARD_DEVIATION 10.05 • n=5 Participants	66.3 years STANDARD_DEVIATION 6.34 • n=7 Participants	51.0 years STANDARD_DEVIATION NA • n=5 Participants	59.1 years STANDARD_DEVIATION 9.91 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	34 Participants n=4 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	30 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	35 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other-unspecified	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Race · Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: up to 14.6 months

Population: Analysis performed on mITT population that included all participants who received at least 1 dose of study drug, and had at least 1 post baseline efficacy assessment. Participants who discontinued prior to first post baseline efficacy assessment were included if discontinuation was due to disease progression, study drug related toxicity, or death.

Outcome measures

Outcome measures
Measure	Cohort 1: Head and Neck-SCC n=33 Participants Participants with advanced SCC of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 2: Lungs-SCC n=4 Participants Participants with advanced SCC of lungs, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 3: Esophagus-SCC n=1 Participants Participants with advanced SCC of esophagus, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.
Percentage of Participants With Disease Control Rate (DCR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	21.2 percentage of participants Interval 10.7 to 37.8	0.0 percentage of participants Interval 0.0 to 49.0	0.0 percentage of participants Interval 0.0 to 79.3

SECONDARY outcome

Timeframe: From the first administration of study drug up to 30 days follow-up (up to 14.6 months)

Population: Analysis was performed on safety population that included all participants who had received any amount of study drug.

An adverse event (AE) was defined as any unfavorable sign and unintended sign (including abnormal laboratory finding), symptom, or disease temporarily associated with the use of the study drug, whether or not related to study drug. An SAE was defined as any untoward medical occurrence that occurs at any dose (including after informed consent was signed and prior to dosing) that resulted in death, was life-threatening (participant was at immediate risk of death from event), required in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect, and important medical events. A TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after first dose of treatment through 30 days following last dose of study treatment, or any event considered drug-related by investigator through end of study.

Outcome measures

Outcome measures
Measure	Cohort 1: Head and Neck-SCC n=37 Participants Participants with advanced SCC of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 2: Lungs-SCC n=5 Participants Participants with advanced SCC of lungs, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 3: Esophagus-SCC n=3 Participants Participants with advanced SCC of esophagus, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Participants with TEAEs	37 Participants	5 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Participants with SAEs	18 Participants	2 Participants	3 Participants

SECONDARY outcome

Timeframe: From the first administration of study drug up to 30 days follow-up (up to 14.6 months)

Population: Analysis was performed on safety population that included all participants who had received any amount of study drug.

AE:Any unfavorable sign and unintended sign,symptom, or disease temporarily associated with use of study drug, whether or not related to it. SAE:Any untoward medical occurrence that occurs at any dose (after informed consent was signed, prior dosing) that resulted in death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, and important medical events. TEAE:Any AE with onset or worsening of existing condition on or after first dose through 30 days following last dose of study drug, or any event considered drug-related by investigator through end of study. Severity(Grades 1 to 5) of each AE was categorized as either mild=1(transient,does not interfere with daily activities), moderate=2(low level of inconvenience or concern,interfere with daily activities), severe=3(interrupt usual daily activities), life threatening=4 or fatal=5, higher grade reported worst outcome.

Outcome measures

Outcome measures
Measure	Cohort 1: Head and Neck-SCC n=37 Participants Participants with advanced SCC of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 2: Lungs-SCC n=5 Participants Participants with advanced SCC of lungs, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 3: Esophagus-SCC n=3 Participants Participants with advanced SCC of esophagus, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.
Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale Mild (Grade 1)	3 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale Moderate (Grade 2)	9 Participants	1 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale Fatal (Grade 5)	1 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale Severe (Grade 3)	21 Participants	4 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale Life Threatening (Grade 4)	3 Participants	0 Participants	0 Participants

Adverse Events

Cohort 1: Head and Neck-SCC

Serious events: 18 serious events

Other events: 35 other events

Deaths: 16 deaths

Cohort 2: Lungs-SCC

Serious events: 2 serious events

Other events: 5 other events

Deaths: 2 deaths

Esophagus-SCC

Serious events: 3 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Jatin Shah, MD

Karyopharm Therapeutics Inc.

Phone: (617) 658-0600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1: Head and Neck-SCC n=37 participants at risk Participants with advanced SCC of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Cohort 2: Lungs-SCC n=5 participants at risk Participants with advanced SCC of lungs, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Esophagus-SCC n=3 participants at risk Participants with advanced SCC of esophagus, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets \<100\*10\^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.
Infections and infestations Pneumonia	13.5% 5/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	20.0% 1/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Infections and infestations Lung Infection	5.4% 2/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Infections and infestations Tracheitis	0.00% 0/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	66.7% 2/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Infections and infestations Arthritis Bacterial	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Infections and infestations Skin Infection	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Infections and infestations Streptococcal Bacteraemia	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	33.3% 1/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Respiratory, thoracic and mediastinal disorders Laryngeal Obstruction	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Respiratory, thoracic and mediastinal disorders Obstructive Airways Disorder	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Respiratory, thoracic and mediastinal disorders Pneumonia Aspiration	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Psychiatric disorders Delirium	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	20.0% 1/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Psychiatric disorders Anxiety	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Gastrointestinal disorders Mouth Haemorrhage	5.4% 2/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Injury, poisoning and procedural complications Spinal Compression Fracture	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Injury, poisoning and procedural complications Tracheal Obstruction	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
General disorders Death	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Investigations Platelet Count Decreased	0.00% 0/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	33.3% 1/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Metabolism and nutrition disorders Hyponatraemia	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.
Vascular disorders Hypotension	2.7% 1/37 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/5 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.	0.00% 0/3 • From the first administration of study drug up to 30 days after participant's last visit (up to 14.6 months) Analysis was performed on safety population that included all participants who had received any amount of study drug.